bluuebunny/crossref_metadata_2025 huggingface dataset:
Review—Catalytic Electrochemical Biosensors for Dopamine: Design, Performance, and Healthcare Applications
Authors: DeVoe Emily , Andreescu Silvana
Published: April 2024

Dopamine is an essential neurotransmitter for daily cognitive functions controlling many neurophysiological processes including memory, cognition, and physical control. Development of analytical methods and sensors to detect dopamine is important for health monitoring and neurological research. This review provides an overview of recent advances in the development of electrochemical catalytic biosensors based on enzyme and enzyme-mimetic materials and discusses their potential applications for measurements of dopamine in biological fluids. The first part of the review summarizes and critically assesses the different types of enzymes and enzyme mimetic materials that can be used to catalytically convert dopamine, followed by a discussion of the biosensor’s fabrication, key design parameters, and detection mechanism on various electrode platforms ranging from single-use screen-printed electrodes to microneedles and implantable microelectrodes. The second part provides examples of measurements of dopamine in biological samples, including saliva, urine, serum, cell cultures, and brain tissue. We conclude with a summary of advantages and limitations of these devices in the clinical field, and an outlook to future research towards the implementation and broader adoption of electrochemical biosensors in neurophysiology, pharmacology, and the clinical field.
Assessment of Urban Blue‐Green Space Landscape Ecological Health Based on the GST‐AHP‐TOPSIS Composite Model
Authors: Cheng Qingtao , Li Qiuping
Published: April 2024

The urban blue‐green space landscape ecology is an important component that supports the urban landscape ecosystem. In this study, a combination model of the grey system theory (GST), analytic hierarchy process (AHP), and technique for order of preference by similarity to ideal solution (TOPSIS) was used to construct criteria layers from the following four aspects: green space vegetation coverage, ecosystem diversity, air and water quality, social participation, and health. The GST method was employed to screen evaluation indicators, the AHP method was used to calculate the weight of each indicator, and finally, TOPSIS was applied for weighted ranking to verify the scientific and rationality of the evaluation system. The results indicated the following: (1) out of 36 indicator factors, 10 were not selected through the GST method; (2) the weight ranking of the criteria layer was as follows, from highest to lowest: D2 ecosystem diversity 0.4816 > D1 green space vegetation coverage 0.2608 > D3 air and water quality 0.1864 > D4 social participation and health 0.0713; and (3) the relative closeness and ranking of different regions in Jinan city were as follows: Da Ming Hu area > Shan Da Lu area > Gu Cheng area > Shang Bu area. This study can help avoid decision‐making errors caused by subjective factors and provide new approaches for the assessment of the ecological health of urban blue‐green space landscapes.
Paediatric Laryngeal Synovial Sarcoma: Dilemmas and Decision-Making
Authors: Shein Gregory , Potter Alison J. , Loo Christine , Smee Robert , Jacobson Ian , Anazodo Antoinette
Published: April 2024

Primary laryngeal synovial sarcoma is a rare head and neck cancer. We describe a case of synovial sarcoma of the larynx in a previously well 9-year-old boy with a one-month history of a progressively enlarging neck lump. He was referred to our institution after incomplete surgical excision of the then undifferentiated neck mass. A partial laryngectomy including wide local excision of the residual mass was performed. An ipsilateral level I-III neck dissection was also performed concurrently. Clear re-excision margins were achieved. The neck nodes were all negative for metastatic disease. Adjuvant local radiotherapy treatment was administered to reduce the probability of local recurrence. Four years following treatment completion, the patient remains in remission with no signs of treatment-related morbidity. A review of the published literature on laryngeal synovial sarcoma was undertaken. This case represents the youngest patient to be diagnosed with the condition. Surgical excision represents the mainstay of treatment of laryngeal synovial sarcoma. At more common sites of disease, adjuvant radiotherapy has been associated with lower rates of recurrence. However, there is the potential for significant morbidity from irradiating the neck of a paediatric patient. This case report explores the challenges in treating young patients with aggressive head and neck cancers when faced with little available evidence to guide decision-making.
Multiobjective Optimization of Diesel Particulate Filter Regeneration Conditions Based on Machine Learning Combined with Intelligent Algorithms
Authors: Wang Yuhua , Li Jinlong , Wang Guiyong , Chen Guisheng , Shen Qianqiao , Zeng Boshun , He Shuchao
Published: April 2024

To reduce diesel emissions and fuel consumption and improve DPF regeneration performance, a multiobjective optimization method for DPF regeneration conditions, combined with nondominated sorting genetic algorithms (NSGA-III) and a back propagation neural network (BPNN) prediction model, is proposed. In NSGA-III, DPF regeneration temperature (T4 and T5), O2,NOx, smoke, and brake-specific fuel consumption (BSFC) are optimized by adjusting the engine injection control parameters. An improved seagull optimization algorithm (ISOA) is proposed to enhance the accuracy of BPNN predictions. The ISOA-BP diesel engine regeneration condition prediction model is established to evaluate fitness. The optimized fuel injection parameters are programmed into the engine’s electronic control unit (ECU) for experimental validation through steady-state testing, DPF active regeneration testing, and WHTC transient cycle testing. The results demonstrate that the introduced ISOA algorithm exhibits faster convergence and improved search abilities, effectively addressing calculation accuracy challenges. A comparison between the SOA-BPNN and ISOA-BPNN models shows the superior accuracy of the latter, with reduced errors and improved R2 values. The optimization method, integrating NSGA-III and ISOA-BPNN, achieves multiobjective calibration for T4 and T5 temperatures. Steady-state testing reveals average increases of 3.14%, 2.07%, and 10.79% in T4, T5, and exhaust oxygen concentrations, while NOx, smoke, and BSFC exhibit average decreases of 8.68%, 12.07%, and 1.03%. Regeneration experiments affirm the efficiency of the proposed method, with DPF regeneration reaching 88.2% and notable improvements in T4, T5, and oxygen concentrations during WHTC transient testing. This research provides a promising and effective solution for calibrating the regeneration temperature of DPF, thus reducing emissions and fuel consumption of diesel engines while ensuring safe and efficient DPF regeneration.
Table S3 from Integrating AI-Powered Digital Pathology and Imaging Mass Cytometry Identifies Key Classifiers of Tumor Cells, Stroma, and Immune Cells in Non–Small Cell Lung Cancer
Authors: Rigamonti Alessandra , Viatore Marika , Polidori Rebecca , Rahal Daoud , Erreni Marco , Fumagalli Maria Rita , Zanini Damiano , Doni Andrea , Putignano Anna Rita , Bossi Paola , Voulaz Emanuele , Alloisio Marco , Rossi Sabrina , Zucali Paolo Andrea , Santoro Armando , Balzano Vittoria , Nisticò Paola , Feuerhake Friedrich , Mantovani Alberto , Locati Massimo , Marchesi Federica
Published: April 2024

Supplementary Table 3
Supplemental Table S5 from Subclonal Cancer Driver Mutations Are Prevalent in the Unresected Peritumoral Edema of Adult Diffuse Gliomas
Authors: Underhill Hunter R. , Karsy Michael , Davidson Christian J. , Hellwig Sabine , Stevenson Samuel , Goold Eric A. , Vincenti Sydney , Sellers Drew L. , Dean Charlie , Harrison Brion E. , Bronner Mary P. , Colman Howard , Jensen Randy L.
Published: April 2024

Supplemental Table S5. Demographics for diffuse glioma patients.
Supplemental Table S2 from Subclonal Cancer Driver Mutations Are Prevalent in the Unresected Peritumoral Edema of Adult Diffuse Gliomas
Authors: Underhill Hunter R. , Karsy Michael , Davidson Christian J. , Hellwig Sabine , Stevenson Samuel , Goold Eric A. , Vincenti Sydney , Sellers Drew L. , Dean Charlie , Harrison Brion E. , Bronner Mary P. , Colman Howard , Jensen Randy L.
Published: April 2024

Supplemental Table S2. Number of PCR cycles used during library preparation and panel capture-enrichment.
Supplemental Table S1 from Subclonal Cancer Driver Mutations Are Prevalent in the Unresected Peritumoral Edema of Adult Diffuse Gliomas
Authors: Underhill Hunter R. , Karsy Michael , Davidson Christian J. , Hellwig Sabine , Stevenson Samuel , Goold Eric A. , Vincenti Sydney , Sellers Drew L. , Dean Charlie , Harrison Brion E. , Bronner Mary P. , Colman Howard , Jensen Randy L.
Published: April 2024

Supplemental Table S1. Alphabetical listing of 115 genes included on the custom-designed, 114 kb, hotspot panel.
Supplemental Figure S4 from Subclonal Cancer Driver Mutations Are Prevalent in the Unresected Peritumoral Edema of Adult Diffuse Gliomas
Authors: Underhill Hunter R. , Karsy Michael , Davidson Christian J. , Hellwig Sabine , Stevenson Samuel , Goold Eric A. , Vincenti Sydney , Sellers Drew L. , Dean Charlie , Harrison Brion E. , Bronner Mary P. , Colman Howard , Jensen Randy L.
Published: April 2024

Supplemental Figure S4. Effects of thresholding on false positives.
Supplemental Figure S1 from Subclonal Cancer Driver Mutations Are Prevalent in the Unresected Peritumoral Edema of Adult Diffuse Gliomas
Authors: Underhill Hunter R. , Karsy Michael , Davidson Christian J. , Hellwig Sabine , Stevenson Samuel , Goold Eric A. , Vincenti Sydney , Sellers Drew L. , Dean Charlie , Harrison Brion E. , Bronner Mary P. , Colman Howard , Jensen Randy L.
Published: April 2024

Supplemental Figure S1. Development of a truth set to benchmark True2 sensitivity.
Supplement 3 from Subclonal Cancer Driver Mutations Are Prevalent in the Unresected Peritumoral Edema of Adult Diffuse Gliomas
Authors: Underhill Hunter R. , Karsy Michael , Davidson Christian J. , Hellwig Sabine , Stevenson Samuel , Goold Eric A. , Vincenti Sydney , Sellers Drew L. , Dean Charlie , Harrison Brion E. , Bronner Mary P. , Colman Howard , Jensen Randy L.
Published: April 2024

VCF file of common SNPs used to remove potential variants during detection.
Supplementary Table S2 from Human Tumor–Associated Macrophages and Neutrophils Regulate Antitumor Antibody Efficacy through Lethal and Sublethal Trogocytosis
Authors: Singhal Sunil , Rao Abhishek S. , Stadanlick Jason , Bruns Kyle , Sullivan Neil T. , Bermudez Andres , Honig-Frand Adam , Krouse Ryan , Arambepola Sachinthani , Guo Emily , Moon Edmund K. , Georgiou George , Valerius Thomas , Albelda Steven M. , Eruslanov Evgeniy B.
Published: April 2024

Supplementary Table S2. Heatmap showing comparisons of the abilities of different types of blood and tumor FcR+ effectors to affect tumor cell growth depending on targeted tAg density, E:T ratios, and anti-tumor Ab isotypes. The indicated FcR+ effectors were added to EGFRhiA431 (high tAg density) or EGFRloA549 (low tAg density) tumor cells at different E:T ratios in the presence of cetuximab (IgG) or IgA anti-EGFR Ab (IgA). The effect on the tumor cell growth was determined at 48 hours using the IncuCyte Live Cell Analysis System. The numbers on the heatmap represent the percent of inhibition of tumor growth. A positive value indicates the inhibition of tumor growth (degrees of red color). A negative value indicates the stimulation of tumor cell growth (degrees of green color). The numbers represent the mean values obtained from experiments shown in Fig.1I, 1K, 4I, and 4J.
Supplementary Table S1 from Human Tumor–Associated Macrophages and Neutrophils Regulate Antitumor Antibody Efficacy through Lethal and Sublethal Trogocytosis
Authors: Singhal Sunil , Rao Abhishek S. , Stadanlick Jason , Bruns Kyle , Sullivan Neil T. , Bermudez Andres , Honig-Frand Adam , Krouse Ryan , Arambepola Sachinthani , Guo Emily , Moon Edmund K. , Georgiou George , Valerius Thomas , Albelda Steven M. , Eruslanov Evgeniy B.
Published: April 2024

Supplementary Table S1. Patient characteristics
Supplementary Figure S7 from Human Tumor–Associated Macrophages and Neutrophils Regulate Antitumor Antibody Efficacy through Lethal and Sublethal Trogocytosis
Authors: Singhal Sunil , Rao Abhishek S. , Stadanlick Jason , Bruns Kyle , Sullivan Neil T. , Bermudez Andres , Honig-Frand Adam , Krouse Ryan , Arambepola Sachinthani , Guo Emily , Moon Edmund K. , Georgiou George , Valerius Thomas , Albelda Steven M. , Eruslanov Evgeniy B.
Published: April 2024

Supplementary Figure S7. (A) Cumulative flow cytometry results showing the ability of blood and tumor FcR+ effectors to kill PKH-67+A431 tumor cells in the presence of nonspecific human IgG1 or IgA2 isotype control Abs (1ug/ml) at a 2:1 E:T ratio in a 12 hrs FACS-based assay. (B and C) Cumulative results showing the kinetics of GFP+A431 tumor cell growth when co-cultured with blood and tumor FcR+ effectors for 48 hrs at a 2:1 E:T ratio in the presence of IgG1 or IgA2 isotype control Abs (1ug/ml) in the IncuCyte® Live Cell Analysis System. (D) Cumulative flow cytometry results showing the ability of blood and tumor FcR+ effectors to kill PKH-67+A549 tumor cells in the presence of nonspecific human IgG1 or IgA2 isotype control Abs (1ug/ml) at a 50:1 E:T ratio in a 12 hrs FACS-based assay. (E and F) Cumulative results showing the kinetics of GFP+A549 tumor cell growth when co-cultured with blood and tumor FcR+ effectors for 48 hrs at a 50:1 E:T ratio in the presence of IgG1 or IgA2 isotype control Abs (1ug/ml) in the IncuCyte® Live Cell Analysis System. All comparisons used one-way ANOVA with Dunnett’s multiple comparisons test. All Data are represented as mean ± SEM. Indicated FcR+ effectors were freshly isolated for all experiments.
Supplementary Figure S6 from Human Tumor–Associated Macrophages and Neutrophils Regulate Antitumor Antibody Efficacy through Lethal and Sublethal Trogocytosis
Authors: Singhal Sunil , Rao Abhishek S. , Stadanlick Jason , Bruns Kyle , Sullivan Neil T. , Bermudez Andres , Honig-Frand Adam , Krouse Ryan , Arambepola Sachinthani , Guo Emily , Moon Edmund K. , Georgiou George , Valerius Thomas , Albelda Steven M. , Eruslanov Evgeniy B.
Published: April 2024

Supplementary Figure S6. (A and B) Representative experiment and summary results showing the effect of indicated blood and tumor FcR+ effectors on the growth of A431 tumor cell spheroids in the presence of cetuximab (1ug/ml). GFP+A431 cells were seeded at 500 cells/well in a round bottom ultra-low adhesion cell culture plate designed to form spheroids. Indicated FcR+ effectors were added at E:T ratio 50:1 into the spheroid cultures. The growth of tumor spheroids was monitored in the IncuCyte® Live Cell Analysis System for 48 hrs. Representative images of GFP+A431 tumor cell spheroids co-cultured with indicated effectors and cetuximab for 48 hrs taken from IncuCyte® Live Cell Analysis System (original magnification x10). Scale bar, 400 µm. Percentage of tumor cell growth inhibition/stimulation in the presence of anti-EGFR Abs was calculated at 48 hrs using the formula: (FI)(A431+Ab)-FI(A431+effectors+Ab)/FI(A431+Ab)x100%, FI-Integrated fluorescence intensity. Data are represented as mean ± SEM. Wilcoxon matched pairs test (n=7). (C) Representative dotplots showing the different levels of ADT mediated by indicated FcR+ effectors co-cultured with spheroids formed with PKH67-labeled A431 cells. FcR+ effectors were co-cultured at a E:T ratio 50:1 in the presence or absence of cetuximab for 12 hrs. Representative results from 1 of 3 experiments are shown. (D and E) Representative experiment and summary results showing the effect of PBN and TAN on the growth of GFP+A431 tumor cell spheroids in the presence of IgA anti-EGFR Ab (IgA) (1ug/ml). Experiments were performed as described in (A and B). Original magnification x10. Scale bar, 400 µm. Data are represented as mean ± SEM. Wilcoxon matched pairs test (n=5). (F) Representative dotplots showing the ADT mediated by PBN and TAN co-cultured with spheroids formed with PKH67-lableld A431 cells. PBN and TAN were co-cultured at a E:T ratio 50:1 in the presence or absence of IgA anti-EGFR Ab for 12 hrs. Representative results from 1 of 3 experiments are shown.
Supplementary Figure S5 from Human Tumor–Associated Macrophages and Neutrophils Regulate Antitumor Antibody Efficacy through Lethal and Sublethal Trogocytosis
Authors: Singhal Sunil , Rao Abhishek S. , Stadanlick Jason , Bruns Kyle , Sullivan Neil T. , Bermudez Andres , Honig-Frand Adam , Krouse Ryan , Arambepola Sachinthani , Guo Emily , Moon Edmund K. , Georgiou George , Valerius Thomas , Albelda Steven M. , Eruslanov Evgeniy B.
Published: April 2024

Supplementary Figure S5. (A) Representative dotplots showing the levels of trogocytosis and killing activity mediated by TAM co-cultured with cetuximab-opsonized PKH67+A431 cells at a 50:1 E:T ratio for 12 hrs in the presence of blocking anti-CD32a Ab (clone 2B6) or blocking anti-CD32a Ab (clone 6G11). (B and C) Summary results showing the levels of trogocytosis (B) and killing activity (C) mediated by blood monocytes and TAM co-cultured with cetuximab-opsonized PKH67+A431 cells at a 50:1 E:T ratio for 12 hrs in the presence of blocking anti-CD32a Ab (clone2B6) or anti-CD32a Ab (clone 6G11). Blocking anti-CD32a Ab were added at concentration (10ug/ml). Summary graphs represent the total tumoricidal activity of effectors that was calculated as described in material and methods. IC Ab-isotype control Abs. (D) Representative experiment and cumulative results showing the kinetics of GFP+A431 tumor cell growth with blood monocytes or TAM at a 50:1 E:T ratio in the presence of cetuximab and blocking anti-CD32a Ab (clone2B6) or blocking anti-CD32a Ab (clone 6G11) in the IncuCyte® Live Cell Analysis System. Percentage of tumor cell growth inhibition/stimulation was calculated at 60 hrs as described earlier. Number of patients included in each analysis is indicated on the graphs. One-way ANOVA with Friedman multiple comparisons test. All data represented as mean ± SEM.
Supplementary Figure S2 from Human Tumor–Associated Macrophages and Neutrophils Regulate Antitumor Antibody Efficacy through Lethal and Sublethal Trogocytosis
Authors: Singhal Sunil , Rao Abhishek S. , Stadanlick Jason , Bruns Kyle , Sullivan Neil T. , Bermudez Andres , Honig-Frand Adam , Krouse Ryan , Arambepola Sachinthani , Guo Emily , Moon Edmund K. , Georgiou George , Valerius Thomas , Albelda Steven M. , Eruslanov Evgeniy B.
Published: April 2024

Supplementary Figure S2. (A-D) The correlation analyses of the ability of blood and tumor-derived FcR+ effectors to regulate A431 tumor cell growth in the presence of anti-EGFR Abs with key clinical parameters of lung cancer patients including tumor type, stage, size, and smoking history. The effect of FcR+ effectors on A431 tumor cell growth was evaluated in the IncuCyte® Live Cell Analysis System. AC-adenocarcinoma, SCC-squamous cell carcinoma. Pearson test. Number of patients included in each analysis is indicated on the graphs.
Supplementary Figure S1 from Human Tumor–Associated Macrophages and Neutrophils Regulate Antitumor Antibody Efficacy through Lethal and Sublethal Trogocytosis
Authors: Singhal Sunil , Rao Abhishek S. , Stadanlick Jason , Bruns Kyle , Sullivan Neil T. , Bermudez Andres , Honig-Frand Adam , Krouse Ryan , Arambepola Sachinthani , Guo Emily , Moon Edmund K. , Georgiou George , Valerius Thomas , Albelda Steven M. , Eruslanov Evgeniy B.
Published: April 2024

Supplementary Figure S1. (A and B) Flow cytometric analysis of indicated markers of NK and DC in the single cell suspension obtained from digested lung tumor. (C) The comparison among the frequencies of tumor FcR+ effectors and lung tumor stages; All data represented as mean ± SEM. One-way ANOVA with Turkey’s multiple comparisons test. (D) Cumulative flow cytometry results showing the ability of blood and tumor FcR+ effectors to kill PKH-67+A431 tumor cells in the presence of nonspecific human IgG1 isotype control Abs (1ug/ml) at a 50:1 E:T ratio in a 12 hrs FACS-based assay. (E) Cumulative results showing the kinetics of GFP+A431 tumor cell growth when co-cultured with blood and tumor FcR+ effectors for 48 hrs at 50:1 E:T ratio in the presence of IgG1 isotype control Abs in the IncuCyte® Live Cell Analysis System. One-way ANOVA with Dunnett’s multiple comparisons test. (F) Cumulative results showing the kinetics of GFP+A431 tumor cell growth co-cultured with PBN isolated from lung cancer patients and healthy volunteers for 48 hrs at a 50:1 E:T ratio in the presence of human IgG1 isotype control Abs in the IncuCyte® Live Cell Analysis System.
Supplementary Table S3 from PRMT1 Sustains De Novo Fatty Acid Synthesis by Methylating PHGDH to Drive Chemoresistance in Triple-Negative Breast Cancer
Authors: Yamamoto Takehiro , Hayashida Tetsu , Masugi Yohei , Oshikawa Kiyotaka , Hayakawa Noriyo , Itoh Mai , Nishime Chiyoko , Suzuki Masami , Nagayama Aiko , Kawai Yuko , Hishiki Takako , Matsuura Tomomi , Naito Yoshiko , Kubo Akiko , Yamamoto Arisa , Yoshioka Yujiro , Kurahori Tomokazu , Nagasaka Misa , Takizawa Minako , Takano Naoharu , Kawakami Koji , Sakamoto Michiie , Wakui Masatoshi , Yamamoto Takushi , Kitagawa Yuko , Kabe Yasuaki , Horisawa Kenichi , Suzuki Atsushi , Matsumoto Masaki , Suematsu Makoto
Published: April 2024

Table S3
Supplementary Table S2 from PRMT1 Sustains De Novo Fatty Acid Synthesis by Methylating PHGDH to Drive Chemoresistance in Triple-Negative Breast Cancer
Authors: Yamamoto Takehiro , Hayashida Tetsu , Masugi Yohei , Oshikawa Kiyotaka , Hayakawa Noriyo , Itoh Mai , Nishime Chiyoko , Suzuki Masami , Nagayama Aiko , Kawai Yuko , Hishiki Takako , Matsuura Tomomi , Naito Yoshiko , Kubo Akiko , Yamamoto Arisa , Yoshioka Yujiro , Kurahori Tomokazu , Nagasaka Misa , Takizawa Minako , Takano Naoharu , Kawakami Koji , Sakamoto Michiie , Wakui Masatoshi , Yamamoto Takushi , Kitagawa Yuko , Kabe Yasuaki , Horisawa Kenichi , Suzuki Atsushi , Matsumoto Masaki , Suematsu Makoto
Published: April 2024

Table S2
Supplementary Fig.S9 from PRMT1 Sustains De Novo Fatty Acid Synthesis by Methylating PHGDH to Drive Chemoresistance in Triple-Negative Breast Cancer
Authors: Yamamoto Takehiro , Hayashida Tetsu , Masugi Yohei , Oshikawa Kiyotaka , Hayakawa Noriyo , Itoh Mai , Nishime Chiyoko , Suzuki Masami , Nagayama Aiko , Kawai Yuko , Hishiki Takako , Matsuura Tomomi , Naito Yoshiko , Kubo Akiko , Yamamoto Arisa , Yoshioka Yujiro , Kurahori Tomokazu , Nagasaka Misa , Takizawa Minako , Takano Naoharu , Kawakami Koji , Sakamoto Michiie , Wakui Masatoshi , Yamamoto Takushi , Kitagawa Yuko , Kabe Yasuaki , Horisawa Kenichi , Suzuki Atsushi , Matsumoto Masaki , Suematsu Makoto
Published: April 2024

Fig.S9
Supplementary Fig.S7 from PRMT1 Sustains De Novo Fatty Acid Synthesis by Methylating PHGDH to Drive Chemoresistance in Triple-Negative Breast Cancer
Authors: Yamamoto Takehiro , Hayashida Tetsu , Masugi Yohei , Oshikawa Kiyotaka , Hayakawa Noriyo , Itoh Mai , Nishime Chiyoko , Suzuki Masami , Nagayama Aiko , Kawai Yuko , Hishiki Takako , Matsuura Tomomi , Naito Yoshiko , Kubo Akiko , Yamamoto Arisa , Yoshioka Yujiro , Kurahori Tomokazu , Nagasaka Misa , Takizawa Minako , Takano Naoharu , Kawakami Koji , Sakamoto Michiie , Wakui Masatoshi , Yamamoto Takushi , Kitagawa Yuko , Kabe Yasuaki , Horisawa Kenichi , Suzuki Atsushi , Matsumoto Masaki , Suematsu Makoto
Published: April 2024

Fig.S7
Supplementary Fig.S3 from PRMT1 Sustains De Novo Fatty Acid Synthesis by Methylating PHGDH to Drive Chemoresistance in Triple-Negative Breast Cancer
Authors: Yamamoto Takehiro , Hayashida Tetsu , Masugi Yohei , Oshikawa Kiyotaka , Hayakawa Noriyo , Itoh Mai , Nishime Chiyoko , Suzuki Masami , Nagayama Aiko , Kawai Yuko , Hishiki Takako , Matsuura Tomomi , Naito Yoshiko , Kubo Akiko , Yamamoto Arisa , Yoshioka Yujiro , Kurahori Tomokazu , Nagasaka Misa , Takizawa Minako , Takano Naoharu , Kawakami Koji , Sakamoto Michiie , Wakui Masatoshi , Yamamoto Takushi , Kitagawa Yuko , Kabe Yasuaki , Horisawa Kenichi , Suzuki Atsushi , Matsumoto Masaki , Suematsu Makoto
Published: April 2024

Fig.S3
Supplementary Fig.S21 from PRMT1 Sustains De Novo Fatty Acid Synthesis by Methylating PHGDH to Drive Chemoresistance in Triple-Negative Breast Cancer
Authors: Yamamoto Takehiro , Hayashida Tetsu , Masugi Yohei , Oshikawa Kiyotaka , Hayakawa Noriyo , Itoh Mai , Nishime Chiyoko , Suzuki Masami , Nagayama Aiko , Kawai Yuko , Hishiki Takako , Matsuura Tomomi , Naito Yoshiko , Kubo Akiko , Yamamoto Arisa , Yoshioka Yujiro , Kurahori Tomokazu , Nagasaka Misa , Takizawa Minako , Takano Naoharu , Kawakami Koji , Sakamoto Michiie , Wakui Masatoshi , Yamamoto Takushi , Kitagawa Yuko , Kabe Yasuaki , Horisawa Kenichi , Suzuki Atsushi , Matsumoto Masaki , Suematsu Makoto
Published: April 2024

Fig.S21
Supplementary Fig.S20 from PRMT1 Sustains De Novo Fatty Acid Synthesis by Methylating PHGDH to Drive Chemoresistance in Triple-Negative Breast Cancer
Authors: Yamamoto Takehiro , Hayashida Tetsu , Masugi Yohei , Oshikawa Kiyotaka , Hayakawa Noriyo , Itoh Mai , Nishime Chiyoko , Suzuki Masami , Nagayama Aiko , Kawai Yuko , Hishiki Takako , Matsuura Tomomi , Naito Yoshiko , Kubo Akiko , Yamamoto Arisa , Yoshioka Yujiro , Kurahori Tomokazu , Nagasaka Misa , Takizawa Minako , Takano Naoharu , Kawakami Koji , Sakamoto Michiie , Wakui Masatoshi , Yamamoto Takushi , Kitagawa Yuko , Kabe Yasuaki , Horisawa Kenichi , Suzuki Atsushi , Matsumoto Masaki , Suematsu Makoto
Published: April 2024

Fig.S20
Supplementary Fig.S18 from PRMT1 Sustains De Novo Fatty Acid Synthesis by Methylating PHGDH to Drive Chemoresistance in Triple-Negative Breast Cancer
Authors: Yamamoto Takehiro , Hayashida Tetsu , Masugi Yohei , Oshikawa Kiyotaka , Hayakawa Noriyo , Itoh Mai , Nishime Chiyoko , Suzuki Masami , Nagayama Aiko , Kawai Yuko , Hishiki Takako , Matsuura Tomomi , Naito Yoshiko , Kubo Akiko , Yamamoto Arisa , Yoshioka Yujiro , Kurahori Tomokazu , Nagasaka Misa , Takizawa Minako , Takano Naoharu , Kawakami Koji , Sakamoto Michiie , Wakui Masatoshi , Yamamoto Takushi , Kitagawa Yuko , Kabe Yasuaki , Horisawa Kenichi , Suzuki Atsushi , Matsumoto Masaki , Suematsu Makoto
Published: April 2024

Fig.S18
Figure S9 from The Imipridone ONC213 Targets α-Ketoglutarate Dehydrogenase to Induce Mitochondrial Stress and Suppress Oxidative Phosphorylation in Acute Myeloid Leukemia
Authors: Su Yongwei , Carter Jenna L. , Li Xinyu , Fukuda Yu , Gray Ashley , Lynch John , Edwards Holly , Ma Jun , Schreiner Patrick , Polin Lisa , Kushner Juiwanna , Dzinic Sijana H. , Buck Steven A. , Pruett-Miller Shondra M. , Hege-Hurrish Katie , Robinson Camenzind , Qiao Xinan , Liu Shuang , Wu Shuangshuang , Wang Guan , Li Jing , Allen Joshua E. , Prabhu Varun V. , Schimmer Aaron D. , Joshi Dhananjay , Kalhor-Monfared Shiva , Watson Iain D. G. , Marcellus Richard , Isaac Methvin B. , Al-awar Rima , Taub Jeffrey W. , Lin Hai , Schuetz John D. , Ge Yubin
Published: April 2024

Supplementary Figure S9
Supplementary Fig.S16 from PRMT1 Sustains De Novo Fatty Acid Synthesis by Methylating PHGDH to Drive Chemoresistance in Triple-Negative Breast Cancer
Authors: Yamamoto Takehiro , Hayashida Tetsu , Masugi Yohei , Oshikawa Kiyotaka , Hayakawa Noriyo , Itoh Mai , Nishime Chiyoko , Suzuki Masami , Nagayama Aiko , Kawai Yuko , Hishiki Takako , Matsuura Tomomi , Naito Yoshiko , Kubo Akiko , Yamamoto Arisa , Yoshioka Yujiro , Kurahori Tomokazu , Nagasaka Misa , Takizawa Minako , Takano Naoharu , Kawakami Koji , Sakamoto Michiie , Wakui Masatoshi , Yamamoto Takushi , Kitagawa Yuko , Kabe Yasuaki , Horisawa Kenichi , Suzuki Atsushi , Matsumoto Masaki , Suematsu Makoto
Published: April 2024

Fig.S16
Figure S6 from The Imipridone ONC213 Targets α-Ketoglutarate Dehydrogenase to Induce Mitochondrial Stress and Suppress Oxidative Phosphorylation in Acute Myeloid Leukemia
Authors: Su Yongwei , Carter Jenna L. , Li Xinyu , Fukuda Yu , Gray Ashley , Lynch John , Edwards Holly , Ma Jun , Schreiner Patrick , Polin Lisa , Kushner Juiwanna , Dzinic Sijana H. , Buck Steven A. , Pruett-Miller Shondra M. , Hege-Hurrish Katie , Robinson Camenzind , Qiao Xinan , Liu Shuang , Wu Shuangshuang , Wang Guan , Li Jing , Allen Joshua E. , Prabhu Varun V. , Schimmer Aaron D. , Joshi Dhananjay , Kalhor-Monfared Shiva , Watson Iain D. G. , Marcellus Richard , Isaac Methvin B. , Al-awar Rima , Taub Jeffrey W. , Lin Hai , Schuetz John D. , Ge Yubin
Published: April 2024

Supplementary Figure S6
Supplementary Fig.S13 from PRMT1 Sustains De Novo Fatty Acid Synthesis by Methylating PHGDH to Drive Chemoresistance in Triple-Negative Breast Cancer
Authors: Yamamoto Takehiro , Hayashida Tetsu , Masugi Yohei , Oshikawa Kiyotaka , Hayakawa Noriyo , Itoh Mai , Nishime Chiyoko , Suzuki Masami , Nagayama Aiko , Kawai Yuko , Hishiki Takako , Matsuura Tomomi , Naito Yoshiko , Kubo Akiko , Yamamoto Arisa , Yoshioka Yujiro , Kurahori Tomokazu , Nagasaka Misa , Takizawa Minako , Takano Naoharu , Kawakami Koji , Sakamoto Michiie , Wakui Masatoshi , Yamamoto Takushi , Kitagawa Yuko , Kabe Yasuaki , Horisawa Kenichi , Suzuki Atsushi , Matsumoto Masaki , Suematsu Makoto
Published: April 2024

Fig.S13
Supplementary Data from Cyclic Fasting–Mimicking Diet Plus Bortezomib and Rituximab Is an Effective Treatment for Chronic Lymphocytic Leukemia
Authors: Raucci Franca , Vernieri Claudio , Di Tano Maira , Ligorio Francesca , Blaževitš Olga , Lazzeri Samuel , Shmahala Anastasiya , Fragale Giuseppe , Salvadori Giulia , Varano Gabriele , Casola Stefano , Buono Roberta , Visco Euplio , de Braud Filippo , Longo Valter D.
Published: April 2024

Supplementary Data
List of Supplementary Information from PRMT1 Sustains De Novo Fatty Acid Synthesis by Methylating PHGDH to Drive Chemoresistance in Triple-Negative Breast Cancer
Authors: Yamamoto Takehiro , Hayashida Tetsu , Masugi Yohei , Oshikawa Kiyotaka , Hayakawa Noriyo , Itoh Mai , Nishime Chiyoko , Suzuki Masami , Nagayama Aiko , Kawai Yuko , Hishiki Takako , Matsuura Tomomi , Naito Yoshiko , Kubo Akiko , Yamamoto Arisa , Yoshioka Yujiro , Kurahori Tomokazu , Nagasaka Misa , Takizawa Minako , Takano Naoharu , Kawakami Koji , Sakamoto Michiie , Wakui Masatoshi , Yamamoto Takushi , Kitagawa Yuko , Kabe Yasuaki , Horisawa Kenichi , Suzuki Atsushi , Matsumoto Masaki , Suematsu Makoto
Published: April 2024

List of Supplementary Information
SFigure6 from Cyclic Fasting–Mimicking Diet Plus Bortezomib and Rituximab Is an Effective Treatment for Chronic Lymphocytic Leukemia
Authors: Raucci Franca , Vernieri Claudio , Di Tano Maira , Ligorio Francesca , Blaževitš Olga , Lazzeri Samuel , Shmahala Anastasiya , Fragale Giuseppe , Salvadori Giulia , Varano Gabriele , Casola Stefano , Buono Roberta , Visco Euplio , de Braud Filippo , Longo Valter D.
Published: April 2024

SFigure6
SFigure2 from Cyclic Fasting–Mimicking Diet Plus Bortezomib and Rituximab Is an Effective Treatment for Chronic Lymphocytic Leukemia
Authors: Raucci Franca , Vernieri Claudio , Di Tano Maira , Ligorio Francesca , Blaževitš Olga , Lazzeri Samuel , Shmahala Anastasiya , Fragale Giuseppe , Salvadori Giulia , Varano Gabriele , Casola Stefano , Buono Roberta , Visco Euplio , de Braud Filippo , Longo Valter D.
Published: April 2024

SFigure2
SFigure1 from Cyclic Fasting–Mimicking Diet Plus Bortezomib and Rituximab Is an Effective Treatment for Chronic Lymphocytic Leukemia
Authors: Raucci Franca , Vernieri Claudio , Di Tano Maira , Ligorio Francesca , Blaževitš Olga , Lazzeri Samuel , Shmahala Anastasiya , Fragale Giuseppe , Salvadori Giulia , Varano Gabriele , Casola Stefano , Buono Roberta , Visco Euplio , de Braud Filippo , Longo Valter D.
Published: April 2024

SFigure1
Table 1 from The Extracellular Niche and Tumor Microenvironment Enhance KRAS Inhibitor Efficacy in Pancreatic Cancer
Authors: Kumarasamy Vishnu , Wang Jianxin , Frangou Costakis , Wan Yin , Dynka Andrew , Rosenheck Hanna , Dey Prasenjit , Abel Ethan V. , Knudsen Erik S. , Witkiewicz Agnieszka K.
Published: April 2024

Transcriptome data
Supplementary Data from The Extracellular Niche and Tumor Microenvironment Enhance KRAS Inhibitor Efficacy in Pancreatic Cancer
Authors: Kumarasamy Vishnu , Wang Jianxin , Frangou Costakis , Wan Yin , Dynka Andrew , Rosenheck Hanna , Dey Prasenjit , Abel Ethan V. , Knudsen Erik S. , Witkiewicz Agnieszka K.
Published: April 2024

Supplementary information
Supplementary Materials and Methods from Osteosarcoma Cells Secrete CXCL14 That Activates Integrin α11β1 on Fibroblasts to Form a Lung Metastatic Niche
Authors: Xu Yanyang , Deng Chuangzhong , Chen Hongmin , Song YiJiang , Xu Huaiyuan , Song Guohui , Wang Xinliang , Luo Tianqi , Chen Weiqing , Ma Jiahui , Zeng Anyu , Huang Shujing , Chen Zhihao , Fu Jianchang , Gong Ming , Tai Yi , Huang Anfei , Feng Huixiong , Hu Jinxin , Zhu Xiaojun , Tang Qinglian , Lu Jinchang , Wang Jin
Published: April 2024

Supplementary materials and methods encompass additional procedures and techniques that were performed but are not extensively discussed in the main text.
Figure S4 from Osteosarcoma Cells Secrete CXCL14 That Activates Integrin α11β1 on Fibroblasts to Form a Lung Metastatic Niche
Authors: Xu Yanyang , Deng Chuangzhong , Chen Hongmin , Song YiJiang , Xu Huaiyuan , Song Guohui , Wang Xinliang , Luo Tianqi , Chen Weiqing , Ma Jiahui , Zeng Anyu , Huang Shujing , Chen Zhihao , Fu Jianchang , Gong Ming , Tai Yi , Huang Anfei , Feng Huixiong , Hu Jinxin , Zhu Xiaojun , Tang Qinglian , Lu Jinchang , Wang Jin
Published: April 2024

Malignant-derived CXCL14 promotes lung metastasis of osteosarcoma xenografts.
Figure S2 from Osteosarcoma Cells Secrete CXCL14 That Activates Integrin α11β1 on Fibroblasts to Form a Lung Metastatic Niche
Authors: Xu Yanyang , Deng Chuangzhong , Chen Hongmin , Song YiJiang , Xu Huaiyuan , Song Guohui , Wang Xinliang , Luo Tianqi , Chen Weiqing , Ma Jiahui , Zeng Anyu , Huang Shujing , Chen Zhihao , Fu Jianchang , Gong Ming , Tai Yi , Huang Anfei , Feng Huixiong , Hu Jinxin , Zhu Xiaojun , Tang Qinglian , Lu Jinchang , Wang Jin
Published: April 2024

Osteosarcoma cells with high metastatic potential constitutively express CXCL14 to promote stem cell-like properties.
Figure S5 from Lactate Utilization Enables Metabolic Escape to Confer Resistance to BET Inhibition in Acute Myeloid Leukemia
Authors: Monteith Andrew J. , Ramsey Haley E. , Silver Alexander J. , Brown Donovan , Greenwood Dalton , Smith Brianna N. , Wise Ashley D. , Liu Juan , Olmstead Sarah D. , Watke Jackson , Arrate Maria P. , Gorska Agnieszka E. , Fuller Londa , Locasale Jason W. , Stubbs Matthew C. , Rathmell Jeffrey C. , Savona Michael R.
Published: April 2024

Figure S5: Oxamate displays minimal toxicity to AML myeloblasts alone. AML myeloblasts were cultured for 72 hr with BETi (0.15 µM) and indicated lactate utilization inhibitors (AZD3965, UK5099, oxamate = 0.1 µM) and viability quantified using a fluorescent plate reader. Viability was quantified relative to cells treated with vehicle control. Each point represents the mean (technical duplicate) value obtained from cells from an individual experiment (n=3).
Table S2 from Immunometabolic Adaptation of CD19-Targeted CAR T Cells in the Central Nervous System Microenvironment of Patients Promotes Memory Development
Authors: Goldberg Lior , Haas Eric R. , Urak Ryan , Vyas Vibhuti , Pathak Khyatiben V. , Garcia-Mansfield Krystine , Pirrotte Patrick , Singhal Jyotsana , Figarola James L. , Aldoss Ibrahim , Forman Stephen J. , Wang Xiuli
Published: April 2024

Supplementary Table 2: A mass cytometry integrative panel with antibodies specific for CAR, cell lineage, metabolic, activation and maturation, proliferation, cell signaling and regulation, and immune checkpoint proteins involved in CAR T cell function.
Table S1 from Immunometabolic Adaptation of CD19-Targeted CAR T Cells in the Central Nervous System Microenvironment of Patients Promotes Memory Development
Authors: Goldberg Lior , Haas Eric R. , Urak Ryan , Vyas Vibhuti , Pathak Khyatiben V. , Garcia-Mansfield Krystine , Pirrotte Patrick , Singhal Jyotsana , Figarola James L. , Aldoss Ibrahim , Forman Stephen J. , Wang Xiuli
Published: April 2024

Supplementary Table 1. Patients’ demographic and clinical characteristics.
Figure S6 from Immunometabolic Adaptation of CD19-Targeted CAR T Cells in the Central Nervous System Microenvironment of Patients Promotes Memory Development
Authors: Goldberg Lior , Haas Eric R. , Urak Ryan , Vyas Vibhuti , Pathak Khyatiben V. , Garcia-Mansfield Krystine , Pirrotte Patrick , Singhal Jyotsana , Figarola James L. , Aldoss Ibrahim , Forman Stephen J. , Wang Xiuli
Published: April 2024

Figure S6. Comparison of pooled human CSF and patients’ day 28 CSF.
Figure S5 from Immunometabolic Adaptation of CD19-Targeted CAR T Cells in the Central Nervous System Microenvironment of Patients Promotes Memory Development
Authors: Goldberg Lior , Haas Eric R. , Urak Ryan , Vyas Vibhuti , Pathak Khyatiben V. , Garcia-Mansfield Krystine , Pirrotte Patrick , Singhal Jyotsana , Figarola James L. , Aldoss Ibrahim , Forman Stephen J. , Wang Xiuli
Published: April 2024

Figure S5. Patients’ CAR T cell products phenotypic composition.
Figure S3 from Immunometabolic Adaptation of CD19-Targeted CAR T Cells in the Central Nervous System Microenvironment of Patients Promotes Memory Development
Authors: Goldberg Lior , Haas Eric R. , Urak Ryan , Vyas Vibhuti , Pathak Khyatiben V. , Garcia-Mansfield Krystine , Pirrotte Patrick , Singhal Jyotsana , Figarola James L. , Aldoss Ibrahim , Forman Stephen J. , Wang Xiuli
Published: April 2024

Figure S3. Patients’ CD8+ CAR T cells reveal spatiotemporal metabolic rewiring.
Figure S1 from Immunometabolic Adaptation of CD19-Targeted CAR T Cells in the Central Nervous System Microenvironment of Patients Promotes Memory Development
Authors: Goldberg Lior , Haas Eric R. , Urak Ryan , Vyas Vibhuti , Pathak Khyatiben V. , Garcia-Mansfield Krystine , Pirrotte Patrick , Singhal Jyotsana , Figarola James L. , Aldoss Ibrahim , Forman Stephen J. , Wang Xiuli
Published: April 2024

Figure S1. Example of gating strategies to detect CAR- and CAR+ T cells.
Figure S5 from Cytidine Deaminase Resolves Replicative Stress and Protects Pancreatic Cancer from DNA-Targeting Drugs
Authors: Lumeau Audrey , Bery Nicolas , Francès Audrey , Gayral Marion , Labrousse Guillaume , Ribeyre Cyril , Lopez Charlene , Nevot Adele , El Kaoutari Abdessamad , Hanoun Naima , Sarot Emeline , Perrier Marion , Pont Frederic , Cerapio Juan-Pablo , Fournié Jean-Jacques , Lopez Frederic , Madrid-Mencia Miguel , Pancaldi Vera , Pillaire Marie-Jeanne , Bergoglio Valerie , Torrisani Jerome , Dusetti Nelson , Hoffmann Jean-Sebastien , Buscail Louis , Lutzmann Malik , Cordelier Pierre
Published: April 2024

Figure S5
Figure S1 from Cytidine Deaminase Resolves Replicative Stress and Protects Pancreatic Cancer from DNA-Targeting Drugs
Authors: Lumeau Audrey , Bery Nicolas , Francès Audrey , Gayral Marion , Labrousse Guillaume , Ribeyre Cyril , Lopez Charlene , Nevot Adele , El Kaoutari Abdessamad , Hanoun Naima , Sarot Emeline , Perrier Marion , Pont Frederic , Cerapio Juan-Pablo , Fournié Jean-Jacques , Lopez Frederic , Madrid-Mencia Miguel , Pancaldi Vera , Pillaire Marie-Jeanne , Bergoglio Valerie , Torrisani Jerome , Dusetti Nelson , Hoffmann Jean-Sebastien , Buscail Louis , Lutzmann Malik , Cordelier Pierre
Published: April 2024

Figure S1
Data from PRMT1 Sustains De Novo Fatty Acid Synthesis by Methylating PHGDH to Drive Chemoresistance in Triple-Negative Breast Cancer
Authors: Yamamoto Takehiro , Hayashida Tetsu , Masugi Yohei , Oshikawa Kiyotaka , Hayakawa Noriyo , Itoh Mai , Nishime Chiyoko , Suzuki Masami , Nagayama Aiko , Kawai Yuko , Hishiki Takako , Matsuura Tomomi , Naito Yoshiko , Kubo Akiko , Yamamoto Arisa , Yoshioka Yujiro , Kurahori Tomokazu , Nagasaka Misa , Takizawa Minako , Takano Naoharu , Kawakami Koji , Sakamoto Michiie , Wakui Masatoshi , Yamamoto Takushi , Kitagawa Yuko , Kabe Yasuaki , Horisawa Kenichi , Suzuki Atsushi , Matsumoto Masaki , Suematsu Makoto
Published: April 2024

Abstract
Triple-negative breast cancer (TNBC) chemoresistance hampers the ability to effectively treat patients. Identification of mechanisms driving chemoresistance can lead to strategies to improve treatment. Here, we revealed that protein arginine methyltransferase-1 (PRMT1) simultaneously methylates D-3-phosphoglycerate dehydrogenase (PHGDH), a critical enzyme in serine synthesis, and the glycolytic enzymes PFKFB3 and PKM2 in TNBC cells. 13C metabolic flux analyses showed that PRMT1-dependent methylation of these three enzymes diverts glucose toward intermediates in the serine-synthesizing and serine/glycine cleavage pathways, thereby accelerating the production of methyl donors in TNBC cells. Mechanistically, PRMT1-dependent methylation of PHGDH at R54 or R20 activated its enzymatic activity by stabilizing 3-phosphoglycerate binding and suppressing polyubiquitination. PRMT1-mediated PHGDH methylation drove chemoresistance independently of glutathione synthesis. Rather, activation of the serine synthesis pathway supplied α-ketoglutarate and citrate to increase palmitate levels through activation of fatty acid synthase (FASN). Increased palmitate induced protein S-palmitoylation of PHGDH and FASN to further enhance fatty acid synthesis in a PRMT1-dependent manner. Loss of PRMT1 or pharmacologic inhibition of FASN or protein S-palmitoyltransferase reversed chemoresistance in TNBC. Furthermore, IHC coupled with imaging MS in clinical TNBC specimens substantiated that PRMT1-mediated methylation of PHGDH, PFKFB3, and PKM2 correlates with chemoresistance and that metabolites required for methylation and fatty acid synthesis are enriched in TNBC. Together, these results suggest that enhanced de novo fatty acid synthesis mediated by coordinated protein arginine methylation and protein S-palmitoylation is a therapeutic target for overcoming chemoresistance in TNBC.
Significance:
PRMT1 promotes chemoresistance in TNBC by methylating metabolic enzymes PFKFB3, PKM2, and PHGDH to augment de novo fatty acid synthesis, indicating that targeting this axis is a potential treatment strategy.
Data from Lactate Utilization Enables Metabolic Escape to Confer Resistance to BET Inhibition in Acute Myeloid Leukemia
Authors: Monteith Andrew J. , Ramsey Haley E. , Silver Alexander J. , Brown Donovan , Greenwood Dalton , Smith Brianna N. , Wise Ashley D. , Liu Juan , Olmstead Sarah D. , Watke Jackson , Arrate Maria P. , Gorska Agnieszka E. , Fuller Londa , Locasale Jason W. , Stubbs Matthew C. , Rathmell Jeffrey C. , Savona Michael R.
Published: April 2024

Abstract
Impairing the BET family coactivator BRD4 with small-molecule inhibitors (BETi) showed encouraging preclinical activity in treating acute myeloid leukemia (AML). However, dose-limiting toxicities and limited clinical activity dampened the enthusiasm for BETi as a single agent. BETi resistance in AML myeloblasts was found to correlate with maintaining mitochondrial respiration, suggesting that identifying the metabolic pathway sustaining mitochondrial integrity could help develop approaches to improve BETi efficacy. Herein, we demonstrated that mitochondria-associated lactate dehydrogenase allows AML myeloblasts to utilize lactate as a metabolic bypass to fuel mitochondrial respiration and maintain cellular viability. Pharmacologically and genetically impairing lactate utilization rendered resistant myeloblasts susceptible to BET inhibition. Low-dose combinations of BETi and oxamate, a lactate dehydrogenase inhibitor, reduced in vivo expansion of BETi-resistant AML in cell line and patient-derived murine models. These results elucidate how AML myeloblasts metabolically adapt to BETi by consuming lactate and demonstrate that combining BETi with inhibitors of lactate utilization may be useful in AML treatment.
Significance:
Lactate utilization allows AML myeloblasts to maintain metabolic integrity and circumvent antileukemic therapy, which supports testing of lactate utilization inhibitors in clinical settings to overcome BET inhibitor resistance in AML.

See related commentary by Boët and Sarry, p. 950
Supplemental Figure 4 from Cytogenetic and Molecular Associations with Outcomes in Higher-Risk Myelodysplastic Syndromes Treated with Hypomethylating Agents plus Venetoclax
Authors: Bazinet Alexandre , Desikan Sai Prasad , Li Ziyi , Rodriguez-Sevilla Juan Jose , Venugopal Sangeetha , Urrutia Samuel , Montalban-Bravo Guillermo , Sasaki Koji , Chien Kelly S. , Hammond Danielle , Kanagal-Shamanna Rashmi , Ganan-Gomez Irene , Kadia Tapan M. , Borthakur Gautam , DiNardo Courtney D. , Daver Naval G. , Jabbour Elias J. , Ravandi Farhad , Kantarjian Hagop , Garcia-Manero Guillermo
Published: April 2024

Supplemental Figure 4: Effect of SCT.
Supplemental Figure 3 from Cytogenetic and Molecular Associations with Outcomes in Higher-Risk Myelodysplastic Syndromes Treated with Hypomethylating Agents plus Venetoclax
Authors: Bazinet Alexandre , Desikan Sai Prasad , Li Ziyi , Rodriguez-Sevilla Juan Jose , Venugopal Sangeetha , Urrutia Samuel , Montalban-Bravo Guillermo , Sasaki Koji , Chien Kelly S. , Hammond Danielle , Kanagal-Shamanna Rashmi , Ganan-Gomez Irene , Kadia Tapan M. , Borthakur Gautam , DiNardo Courtney D. , Daver Naval G. , Jabbour Elias J. , Ravandi Farhad , Kantarjian Hagop , Garcia-Manero Guillermo
Published: April 2024

Supplemental Figure 3: Overall survival and event-free survival in CMML.
Supplemental Figure 1 from Cytogenetic and Molecular Associations with Outcomes in Higher-Risk Myelodysplastic Syndromes Treated with Hypomethylating Agents plus Venetoclax
Authors: Bazinet Alexandre , Desikan Sai Prasad , Li Ziyi , Rodriguez-Sevilla Juan Jose , Venugopal Sangeetha , Urrutia Samuel , Montalban-Bravo Guillermo , Sasaki Koji , Chien Kelly S. , Hammond Danielle , Kanagal-Shamanna Rashmi , Ganan-Gomez Irene , Kadia Tapan M. , Borthakur Gautam , DiNardo Courtney D. , Daver Naval G. , Jabbour Elias J. , Ravandi Farhad , Kantarjian Hagop , Garcia-Manero Guillermo
Published: April 2024

Supplemental Figure 1: Overall survival and event-free survival in HMA-naïve patients by response.
Supplementary Table S3 from Combined Vorinostat and Chloroquine Inhibit Sodium–Iodide Symporter Endocytosis and Enhance Radionuclide Uptake In Vivo
Authors: Read Martin L. , Brookes Katie , Zha Ling , Manivannan Selvambigai , Kim Jana , Kocbiyik Merve , Fletcher Alice , Gorvin Caroline M. , Firth George , Fruhwirth Gilbert O. , Nicola Juan P. , Jhiang Sissy , Ringel Matthew D. , Campbell Moray J. , Sunassee Kavitha , Blower Philip J. , Boelaert Kristien , Nieto Hannah R. , Smith Vicki E. , McCabe Christopher J.
Published: April 2024

Supplementary Table S3
Supplementary Figure S7 from Combined Vorinostat and Chloroquine Inhibit Sodium–Iodide Symporter Endocytosis and Enhance Radionuclide Uptake In Vivo
Authors: Read Martin L. , Brookes Katie , Zha Ling , Manivannan Selvambigai , Kim Jana , Kocbiyik Merve , Fletcher Alice , Gorvin Caroline M. , Firth George , Fruhwirth Gilbert O. , Nicola Juan P. , Jhiang Sissy , Ringel Matthew D. , Campbell Moray J. , Sunassee Kavitha , Blower Philip J. , Boelaert Kristien , Nieto Hannah R. , Smith Vicki E. , McCabe Christopher J.
Published: April 2024

Supplementary Figure S7
Supplementary Figure S6 from Combined Vorinostat and Chloroquine Inhibit Sodium–Iodide Symporter Endocytosis and Enhance Radionuclide Uptake In Vivo
Authors: Read Martin L. , Brookes Katie , Zha Ling , Manivannan Selvambigai , Kim Jana , Kocbiyik Merve , Fletcher Alice , Gorvin Caroline M. , Firth George , Fruhwirth Gilbert O. , Nicola Juan P. , Jhiang Sissy , Ringel Matthew D. , Campbell Moray J. , Sunassee Kavitha , Blower Philip J. , Boelaert Kristien , Nieto Hannah R. , Smith Vicki E. , McCabe Christopher J.
Published: April 2024

Supplementary Figure S6
Supplementary Figure S4 from Combined Vorinostat and Chloroquine Inhibit Sodium–Iodide Symporter Endocytosis and Enhance Radionuclide Uptake In Vivo
Authors: Read Martin L. , Brookes Katie , Zha Ling , Manivannan Selvambigai , Kim Jana , Kocbiyik Merve , Fletcher Alice , Gorvin Caroline M. , Firth George , Fruhwirth Gilbert O. , Nicola Juan P. , Jhiang Sissy , Ringel Matthew D. , Campbell Moray J. , Sunassee Kavitha , Blower Philip J. , Boelaert Kristien , Nieto Hannah R. , Smith Vicki E. , McCabe Christopher J.
Published: April 2024

Supplementary Figure S4