bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intensive Chemotherapy Sequential with Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Refractory or Relapsed Acute Myeloid Leukemia: Case Series, Systematic Review and Meta-Analysis
Authors: Yan Jinsong , Hu Jiong , Zheng Jin , Liu Lusi , Li Chunhong 
Published: December 2024

Background: One important therapeutic approach to refractory and relapsed acute myeloid leukemia (R/R AML) is allogeneic hematopoietic stem cell transplantation (allo-HSCT). For patients with R/R AML, however, the effectiveness of conventional conditioning regimens is limited. Of note, intensive chemotherapy sequential with a conditioning regimen has emerged as an effective treatment modality for leukemic cytoreduction in R/R AML. We retrieved relevant studies for systematic review and meta-analysis to understand the effects of intensive chemotherapy sequential with a conditioning regimen for R/R AML patients and reported a case series in our medical center to validate.
Methods: We searched literature from PubMed, Web of Science, EMBASE, the Cochrane Library, and ClinicalTrials.gov through July 2023 and collected 16 relevant cases in the single center to evaluate. We conducted all analyses using R software version 4.3.1. The pooled primary outcomes included the overall-survival (OS) rate and leukemia-free survival (LFS) rate of meta-analysis. The Kaplan-Meier method was used to calculate OS in the single center.
Results: The meta-analysis revealed a pooled 2-year OS rate of 38% (95% confidence interval [CI], 35-42%; I² = 57%, P = 0.01), a LFS rate of 34% (95% CI, 29-40%; I² = 73%; P &lt; 0.01), and a 2-year non-relapse mortality (NRM) rate of 20% (95% CI, 17-23%; I² = 74%; P &lt; 0.01). The 2-year OS rate in our case series was the same as that in our meta-analysis.
Conclusion: For R/R AML patients, intensive chemotherapy with sequential allo-HSCT demonstrated a promising trend toward a better OS and LFS, a reduced relapse rate, and a lower NRM. However, we need a prospective study with an even larger sample size to prove these findings.
Alpha-Enolase (ENO1) Promotes AML Progression Via the MAPK/ERK Pathway
Authors: Zhang Shanshan , Wang Haina , Yan Jinsong , Hu Jiong , Sun Mingzhong 
Published: December 2024

Abstract：
Acute Myeloid Leukemia (AML) is a malignant clonal disease of the blood system, characterized by abnormal proliferation and impaired differentiation of myeloid cells, resulting in the accumulation of leukemia cells and abnormal hematopoietic function. Although targeted therapy has developed rapidly, drug resistance and relapse remain major challenges in AML treatment. Exploring the abnormal proteins driving leukemia development and searching for new therapeutic targets and drugs are key tasks for AML treatment.
Enolase-1 (ENO1) is a key enzyme in the glycolysis process, and its abnormal expression drives the development of various cancers. To clarify the role of ENO1 in the progression of AML, we studied the relationship between ENO1 and AML using database and patient transcriptome sequencing datafrom 185 AML patient samples. Our results confirm that ENO1 is highly expressed in AML patients and is associated with poor clinical outcomes. Knockdown of ENO1 in AML cells significantly inhibited their proliferation, cloning, migration, and invasion in vitro, blocked the cell cycle, and promoted apoptosis. We found that ENO1 was closely related to mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway through cell transcriptome sequencing data analysis. ERK pathway inhibitors significantly inhibited proliferation, clonal formation, migration, and invasion of AML cells in vitro, blocked cell cycle, and promoted apoptosis. And knockdown of ENO1 significantly inhibited ERK pathway proteins' phosphorylation. Most importantly, activators of ERK pathway could reverse the effects of ENO1 knockdown on AML cells. We also found that ENO1 knockdown inhibited the proliferation and invasion of AML cells in mice and significantly increase the overall survival rate of mice.
Altogether, these results not only reveal the role and mechanism of ENO1 in the development of AML but also highlight ENO1 as a potential therapeutic target in the treatment of AML.
Key words: AML, ENO1, Cell proliferation, Invasion
Huaier Inhibits the Stemness and Drug Resistance Via Regulating WNT/β-Catenin and YAP Signaling Pathways in IKZF1del-Ph+ALL
Authors: Huang Ziyi , Zhou Fen , Shang Mengxuan , Han Juan , Qu Ping , Shi Hui , Cheng Yiren 
Published: December 2024

Background: With the development of TKIs, the prognosis of Ph+ALL has been significantly improved. However, Ph+ALL especially with IKZF1 deletion are more likely to relapse and drug resistance. Huaier is a tranditional Chinese medicine, which has been shown an effective adjuvant of cancer therapy. .Our study aims to explore the effect and mechanism of Huaier on the chemosensitivity of IKZF1del-Ph+-ALL.
Methods: Cell viability was analysed by CCK8 and High-throughput Drug Sensitivity Analysis Strategy. Flow cytometry was used to detect cell apoptosis, cell cycle and adhesion markers. RNAseq, RT-PCR and Western blot were conducted to discover the related gene and protein expresson of stemness pathway.
Results: Our studies demonstrated that Huaier enhanced the efficacy of chemotherapy. Using the concentration of GI25, GI50 and GI75 of Huaier combined with VDLP, dasatinib, mercaptopurine and methotrexate, it was found that Huaier could improve the cell inhibition rate of these chemotherapy drugs. Huaier combined with dasatinib could significantly increased the apoptosis of Sup-B15 cells (Control group vs. dasatinib group vs. Huaier group vs. Huaier + dasatinib group: 7.70%±0.67% vs. 58.70%±0.35% vs. 60.97%±0.55% vs. 73.17%±0.44%, p &lt; 0.0001), arrested the cell cycle in the G0/G1 phase (Control group vs. dasatinib group vs. Huaier group vs. Huaier + dasatinib group: 46.70%±0.05% vs. 53.74%±0.82% vs. 58.63%±0.01% vs. 63.70%±0.69%, p &lt; 0.0001) and reduced the expression of adhesion-related molecules, such as the mRNA expression of ITGA4, ITGA8, THY-1, ITGA9 (p &lt; 0.0001), ITGA5 (p = 0.0231), and the protein expression of FAK (p &lt; 0.0001) and phosphorylated FAK (p = 0.0026).
The result of RNAseq showed that the differentially expressed genes were enriched in stemness-related pathways, among which Wnt/β-catenin and YAP were significantly down-regulated. The mRNA expression of wnt3, wnt3a, DVL-3, c-myc, FZ2, TCF-1, c-jun and cyclinD1 was significantly decreased (P &lt; 0.0001). Also, the WNT pathways downstream of the key moleculars protein expression of β-catenin, c-myc, c-jun, TCF1, TCF3, TCF4 (P &lt; 0.01) and corresponding phosphorylated proteins (P &lt; 0.05) were all decreased. Also the mRNA (P &lt; 0.0001) and protein expression of YAP, CTGF and survivin were significantly decreased (P &lt; 0.01) after Huaier treatment.
Conclusions: In our study, we proved that Huaier can inhibit the Wnt/β-catenin and YAP pathway to enhance the chemotherapy sensitivity of Ph+ALL.Therefore, Huaier has great potential for clinical application in the treatment of refractory/relapsed Ph+ALL.
Improving Resident Education & Comfort of Key Hematology, Oncology and Bone Marrow Transplant Topics
Authors: Aryee Emmanuel , Oduro Joana , LaCroix Megan , Graff Zachary 
Published: December 2024

Background
Patients admitted to the Hematology, Oncology, and Transplant (HOT) unit often have specific needs and challenges which are often not encountered in other rotations. Unfamiliarity with the patient population and unit-specific knowledge and procedures have occasionally led to adverse outcomes as well as patient morbidity and mortality. Residents have reported knowledge gaps for HOT unit specific topics and expressed interest in both formal and informal didactic opportunities to improve patient care.
Objective
This is a quality improvement project designed to improve overall resident comfort levels in hematology, oncology and bone marrow transplant topics during residents' rotation in the HOT unit.
Design/Methods
We designed a “bingo” card of high yield topics that residents would likely encounter in the HOT unit. Paper copies were provided to residents in the beginning of their rotation. QR codes with copies of the “bingo” cards were also placed throughout the unit. Both resident and faculty were educated about the intervention and encouraged to utilize the cards during and after morning rounds. Whenever a topic was discussed, the corresponding box on the “bingo” card was marked as completed and signed by a faculty member. Residents turned in the “bingo” cards at the end of the rotation. A subsequent survey of resident perceived knowledge and comfort level with key topics and concepts on a 10-point Likert scale was conducted at the end of the rotation. We then conducted a pre-post analysis comparing resident knowledge of key topics before the rotation with their comfort and knowledge after the rotation. We additionally conducted a retrospective survey of resident who completed the rotation before the introduction of the “bingo” card to assess the utility of the intervention.
Results
Residents reported the greatest improvement in knowledge and management scores (5-6) on topics they were unlikely to encounter in other rotations such as Oncologic emergencies, Veno-occlusive disease (VOD) and Engraftment Syndrome as compared to cross-disciplinary topics like pain, nausea and decreased food intake (3-4). There were no differences found in the knowledge scores of residents who completed the rotation prior the introduction of the “bingo” card intervention. Residents who completed the rotation post intervention however reported finding the intervention helpful to their learning (80%).
Conclusion
Resident knowledge and comfort of key Hematology, Oncology and Bone Marrow Transplant topics improves after their rotation. This is particularly salient on topics that are not covered in other rotations. Introduction of a “bingo” card to promote learning was successful in engaging residents and helping them learn.
Clinical Characteristics and Prognostic Significance of PWWP2B Expression in AML Patients Treated with Intensive Chemotherapy
Authors: Chen Cheng-Yeh , Tsai Xavier Cheng-Hong , Sun Kuojui , Tien Feng-Ming , Kuo Yuan-Yeh , Tseng Mei-Hsuan , Peng Yen-Ling , Ko Bor-Sheng , Liu Ming-Chih , Liu Chia-Wen , Lin Chien-Chin , Yao Ming , Chou Wen-Chien , Tien Hwei-Fang , Hou Hsin-An 
Published: December 2024

Background/Aim
PWWP domain containing 2b (PWWP2B) is a nuclear protein, which was reported to participate in the regulation of histone acetylation and chromatin modifying by forming complex with histone deacetylases (HDAC) proteins. HDACs are known to involve in chromatin remodeling. Abnormal HDACs functions may contribute to the leukemogenesis of acute myeloid leukemia (AML). Therefore, this study aimed to investigate the prognostic significance of PWWP2B expression in AML patients.
Methods
A total of 475 adult patients with newly diagnosed de novo non-M3 AML at the National Taiwan University Hospital, treated with intensive chemotherapy, were consecutively enrolled. PWWP2B expression level was detected by RNA sequencing assay. Maximally selected rank statistics were employed to find the optimal cutoff point for PWWP2B expression in survival analysis. Survival analyses were performed using the Kaplan-Meier model and the Cox proportional hazards model was used for multivariable analysis. Bioinformatics approaches for biological inference was conducted by Ingenuity Pathway Analysis.
Results
The ELN-2022 risk stratification of our AML patient cohort was as follows: 40.6% (n=193) classified as favorable, 28.2% (n=134) as intermediate, and 31.2% (n=148) as adverse. Higher PWWP2B expression was observed in AML patients compared to healthy donors (p&lt;0.001). There is no significant difference in ELN-2022 risk stratification, age, initial leukocyte count, or gender between patients with higher and lower PWWP2B expression levels. Patients with higher PWWP2B expression had higher frequency of concurrent FLT3-ITD and SRSF2 mutation, but lower frequency of NRAS mutations. In terms of treatment outcome, AML patients with higher PWWP2B expression had a worse overall survival (OS) and relapse-free survival (RFS) compared to AML patient with lower expression (P &lt;0.001 for OS and 0.003 for RFS). In multivariate analysis, higher PWWP2B expression level remained an independent adverse prognostic factor for both OS (HR 1.753, p&lt;0.001) and RFS (HR 1.658, p=0.005) irrespective of age, ELN-2022, and leukocyte count at diagnosis. Intriguingly, allogeneic transplantation may overcome the poor prognosis associated with higher PWWP2B expression in AML.
Conclusions
We found that PWWP2B expression has prognostic significance in de novo AML patient treated with intensive chemotherapy. Higher PWWP2B expression is associated with worse survival outcomes. These findings suggest further investigation of HDAC targeted therapy in AML patient with high PWWP2B expression.
Clinical Significance of Genomic Landscape in Pediatric Advanced MDS
Authors: Liu Chenmeng , Wang Xingchen , Chen Yunlong , Wan Yang , An Wenbin , Ren Yuanyuan , Liu Fang , Guo Ye , Yang Wenyu , Zhu Xiaofan 
Published: December 2024

Pediatric advanced myelodysplastic syndrome (MDS) is characterized by a dismal prognosis and a high frequency of mutations. In this study we aimed to assess the clinical significance of genomic landscape in pediatric advanced MDS. We performed next generation sequencing on the bone marrow sample of 72 children with diagnoses of advanced MDS, including RAEB(n=54) and RAEB-T(n=18), targeting genes closely associated with MDS or other hotspots from adult and pediatric myeloid neoplasms.
With only mutations with presumed functional consequences being considered, 83.3% of patients carried gene mutation. We found frequent mutations in PTPN11 (16 cases, 22.2%), SETBP1(14 cases, 19.4%), NRAS (12 cases, 16.7%), RUNX1(10 cases, 13.9%), NF1(9 cases, 12.5%), FLT3(8 cases, 11.1%), GATA2(8 cases, 11.1%), WT1(8 cases, 11.1%). PTPN11 was the most commonly mutated gene. In total, genes involved in the RAS/MAPK pathway, were the most common gene mutations（32 cases,44.4%). We found significant co-occurrence between PTPN11 and NF1 mutations (P=0.003), SETBP1 and EZH2 mutations (P=0.021), SETBP1 and GATA2 mutations (P=0.041), FLT3 and WT1 mutations (P=0.026). SETBP1 and GATA2 alterations were frequently detected in patients with monosomy 7(P&lt;0.001). Children with mutations involved in the RAS-MAPK pathway displayed elevated blast percentages in both BM (14.25% VS 8%, P=0.018) and PB (4% VS 1%, P=0.024), and they also demonstrated a significantly higher likelihood of detecting splenomegaly (P = 0.007). A total of 63 children were available for follow-up. The median follow-up of the entire cohort of children was 27 months (range, 1-116 months). Although not statistically significant, alterations in PTPN11 appeared to be linked with an unstable disease progression. Children with PTPN11 mutations who did not undergo HSCT died within 3 to 18 months after diagnosis, except for one who was lost to follow-up three months post-diagnosis. In contrast, those who underwent HSCT achieved complete remission and remained alive at the last follow-up. Mutations in PTPN11 were significantly correlated with unfavorable EFS (HR:2.909, 95%CI: 1.303-6.495, P=0.009). Patients with mutated genes involved in the RAS/MAPK pathway exhibited similar event-free survival (EFS) and overall survival (OS) compared to those without such mutations. Overall, mutations in RAS/MAPK pathway are the most common genetic alterations in advanced pediatric MDS. PTPN11 alterations were associated with unfavorable EFS.
Zanubrutinib As Salvage Therapy for Refractory/Relapsed Hemophagocytic Lymphohistiocytosis in Adults: A Single Center, Prospective Study
Authors: Wang Jingshi , Song Deli , Wu Lin , Wei Na , Pi Yubo , Wang Zhao 
Published: December 2024

Background：Uncontrolled immune activation and severe inflammation are the hallmarks of hemophagocytic lymphohistiocytosis (HLH) with no treatment response in approximately 30% of patients. With no established salvage treatment, ability of burton tyrosine kinase (BTK) inhibitors to resolve inflammations might be relevant treatment option for HLH. Here, we evaluated the efficacy and safety of zanubrutinib in patients with refractory/relapsed HLH.
Methods：In this single-center, single arm, prospective trial, HLH patients were treated with 160 mg zanubrutinib twice daily for 8 weeks. Efficacy in terms of overall response (OR), complete response (CR) and partial response (PR) at 2, 4, 6, and 8 weeks along with safety was assessed.
Results: A total of 16 patients were enrolled who had a median age of 33.5 years (range 19-74 years) and most patients had connective tissue diseases (n=9; 56.3%). Overall response (OR) after 2 weeks of treatment was 86.7% among with 1 (6.7%) and 12 (80%) patients achieved CR and PR respectively. After 8 weeks, 8 patients were excluded due to various clinical reasons and all the remaining 8 patients achieved CR. Among the 9 patients with macrophage activation syndrome (MAS), 5 (62.5%) achieved CR at 8 weeks. Proinflammatory cytokines, IL-1, IL-10, and IFN-γ significantly decreased (P&lt;0.05) 2 weeks post-zanubrutinib. Fatigue, ecchymosis, and nausea were the most common adverse events and 1 patient died due to cerebral infarction combined with cerebral hemorrhage.
Conclusions: Zanubrutininb showed promising efficacy making it an effective candidate for HLH salvage therapy. However, further confirmations with large-scale studies would be welcoming.
Myeloma-Associated Macrophages Protect Tumor Cells By Reprogramming of Lipid Metabolism through SREBP1
Authors: Guo Xing , Dai Zhenfeng , Zhang Enfan , Cai Zhen 
Published: December 2024

Introduction: With the development of novel therapeutic agents, the survival of multiple myeloma (MM) patients has significantly improved. However,MM remains incurable due to drug resistance. Hence, there is an urgent need to develop novel therapeutic targets and agents. Lipid metabolism disorder is one of the important characteristics of drug-resistant myeloma cells. While statins can induce drug resistance by regulating lipid metabolism in MM and can also increase MM cells' sensitivity to chemotherapy, the key factors in MM cells' lipid metabolism remain u unrevealed. Myeloma-associated macrophages (mMΦs) are prominent components in the bone marrow of MM patients and induce drug resistance by protecting tumor cells from chemotherapy-induced apoptosis. However, no studies have investigated whether mMΦs regulate lipid metabolism of myeloma cells. Therefore, our study aims to explore the role of mMΦs in MM lipid metabolism, and further understand the molecular mechanisms involved.
Results: Our study found that the fatty acid (FA) in MM cells increased significantly after cocultured with mMφs detected by flow cytometry, and FA could protect MM cells from apoptosis induced by bortezomib, which suggested that mMφs could probably induce MM drug resistance through lipid metabolism regulation. To explore the molecular mechanisms in the process, RNA sequencing was used to detect the differential genes expression involved in lipid metabolism cocultured with or without mMφs. We further found that expression of SREBP1, a key transcription factor of FA synthesis increased significantly in MM cells after cocultured with mMφs. And the result was validated by qPCR and western blot. Importantly, we found that SREBP1 in CD138+ plasma cells of relapsed myeloma patients was significantly higher than that of newly diagnosed patients by double immunofluorescence techniques.
Conclusion: Our study found that mMφs may promote FA synthesis in MM cells through regulating SREBP1, and ultimately induce MM drug resistance, which suggested that lipid metabolism pathway is a possible target for MM treatment.
Dilute Russell's Viper Venom Time Correction Ratio and Thrombosis: A Single Centre Retrospective Cohort Study
Authors: Chao David , Tian Ke , Kwok Andrew John , Chan Natalie PH , Wong Raymond SM 
Published: December 2024

Background: Antiphospholipid syndrome (APS) is a thrombo-inflammatory disorder associated with significant morbidity and mortality. In the diagnosis of APS, lupus anticoagulant (LA) testing plays a crucial role. This testing involves assessing the presence of LA using a correction ratio calculated from the dilute Russell's Viper venom Time (dRVVT), a functional assay. Additionally, other antiphospholipid antibodies, such as anti-cardiolipin and anti-beta-2 glycoprotein I, have demonstrated a positive correlation between their titers and thrombotic events.
Aim: This study aims to evaluate the hypothesis that the correction ratio derived from dRVVT can predict the risk of thrombosis in patients who have tested positive for LA on more than one occasion.
Patients and methods: We conducted a single center retrospective cohort study, focusing on patients who are repeatedly tested positive for LA between September 2020 and June 2023. A total of 167 patients were included in the analysis. The mean age of the cohort was 50.4 years (±16.8), with 43.7% male and 56.3% female. We calculated both the highest and mean dRVVT correction ratios. Logistic regression was employed, with thrombosis as the dependent variable. Additionally, we performed a receiver operating characteristic (ROC) analysis to assess the predictive quality of the proposed model. Finally, we stratified the population into quartiles to illustrate the escalating risk of thrombosis at higher correction ratio quartiles.
Results: Among the 167 patients, 63 (37.7%) developed thrombosis. After adjusting for confounding factors, the odds ratio for thrombosis occurrence is 40.9 (95% CI [10.6-157.7], p &lt; 0.01) per 1-unit increase in the highest dRVVT correction time. Similarly, the odds ratio for thrombosis occurrence is 72.2 (95% CI [14.2-367.8], p &lt; 0.01) per 1-unit increase in the mean correction ratio. Additionally, a Pearson's correlation test revealed that the highest dRVVT correlates with activated partial thromboplastin time (APTT). Using the same logistic regression model, the odds ratio for thrombosis occurrence is 1.052 (95% CI [1.023-1.081], p &lt; 0.01) per 1-unit increase in APTT when adjusted for covariates. Furthermore, ROC-AUC analysis demonstrated an area under the curve (AUC) of 0.805 (95% CI [0.735-0.874]). Quartile analysis revealed that the odds ratio for developing thrombosis in the 4th quartile, compared to the 1st quartile, is 30.5 (95% CI [9.8-113.9], p &lt; 0.01).
Conclusion: The correction ratio derived from the dRVVT test positively correlates with thrombotic events. Our data suggest that dRVVT should be further studied as a predictive model for thrombosis.