tbuckley/cabot-search huggingface dataset:
AB0135 Decreased Lupus Manifestations in Pristane-Induced Microrna 155-Deficient Mice
Authors: H. Leiss, W. Salzberger, B. Jacobs, I. Gessl, N. Kozakowski, S. Blüml, A. Puchner, B. Niederreiter, T. Shvets, C.W. Steiner, J. Smolen, G. Stummvoll
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Deregulation of endogenous miR155 was observed in many autoimmune conditions, including systemic lupus erythematosus (SLE). <h3>Objectives</h3> We herein examined the role of miR155 in the development of systemic manifestations in mice with pristane-induced lupus (PIL). <h3>Methods</h3> MiR155-deficient and C57/Bl6 mice were injected with pristane or PBS as control and analyzed after 8 months. Glomerulonephritis and pneumonitis were quantified by using the composite kidney biopsy score (KBS) and by analyzing the numbers of affected lung-vessels and the area of the inflammatory lung-infiltrate, respectively. Specimens were stained with B220 (B), CD3 (T), Neu7/4 (neutrophils) and F4/80 (macrophages) and analyzed by cell-identification algorithms for nuclear segmentation (HistoQuest). Serum levels of anti-dsDNA, anti-histone and anti-chromatin antibodies were measured by ELISA. Frequencies of B cells, activated and regulatory CD4+ T cells as well as Th1, Th2, Th17 cells were measured by flow cytometry. Quantitative real-time polymerase chain reaction was used to measure expression levels of interferon-signature and T-cell subset related as well as miR155-associated genes. <h3>Results</h3> All pristane-injected mice showed signs of pneumonitis, while controls did not. Compared to wild types treated with pristane, similarly treated knockouts showed significantly decreased perivascular inflammatory area with B cells being the most prominent inflammatory cell. Wildtypes had a more severe renal involvement in the KBS than knockouts. Corresponding with reduced organ involvement, miR155 deficient mice had significantly lower serum levels of anti-dsDNA antibodies, anti-chromatin and anti-histone antibodies and decreased frequencies of activated CD4<sup>+</sup>CD25<sup>+</sup>(Foxp3<sup>–</sup>) cells. Interestingly, also frequencies of CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> regulatory T cells were lower in these mice. Upon restimulation, CD4<sup>+</sup> cells showed a more pronounced Th2 response in wild types, but no significant differences in Th1 and Th17 phenotype. Regarding INF-signature and T-cell subset activation, pristane-treated wild types showed significantly up-regulated gene-expression patterns whereas equivalently treated mutants showed the same levels as PBS-treated controls. <h3>Conclusions</h3> MiR155 deficiency in PIL mice did not prevent disease, but was associated with less severe organ involvement, lower serum auto-abs levels, lower frequencies of Th2 cells, whereas lower expressions of genes jointly responsible for disease development may be one key mechanism. Thus, antagonisation of miR155 might be a future approach in treating SLE. <h3>Disclosure of Interest</h3> None declared
Alliance A061202. a Phase I/II Study of Pomalidomide, Dexamethasone and Ixazomib Versus Pomalidomide and Dexamethasone for Patients with Multiple Myeloma Refractory to Lenalidomide and Proteasome Inhibitor Based Therapy: Phase I Results
Authors: Peter M. Voorhees, Flora Mulkey, Hani Hassoun, Claudia E. Paba-Prada, Yvonne A. Efebera, Eva Hoke, Guadalupe Aquino, Destin Carlisle, Vera Suman, Paul G. Richardson
Journal: Blood (2015)
AB0540 Post-Thrombotic Syndrome and Venous Disease Spesific Quality of Life in Patients with Vascular Behçet's Disease: Table 1.
Authors: F. Alibaz-Oner, B. Aldag, M. Aldag, A.U. Unal, A. Mutis, T. Toptas, T. Ergun, H. Direskeneli
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Behçet9s disease (BD) is a systemic disease characterized by oral aphthosis, genital ulcers, ocular lesions and systemic involvement including major vessels. Vascular Behçet9s disease (VBD) is observed in up to 40% of BD. It is one of the major causes ofmorbidity and mortality in BD. Deep venous thrombosis (DVT) is the most common form of vascular involvement in Behcet9s disease (BD). Post-thrombotic syndrome (PTS) develops in up to one-half of patients with DVT and is associated with impaired quality of life (QoL). There is no data on severity of DVT related PTS and its impact on quality of life in patients with Vascular Behçet9s Disease (VBD). <h3>Objectives</h3> We aimed to evaluate frequency of PTS and venous disease spesific QoL in VBD and to compare it with patients having DVT associated with non-Behçet9s disease (NBD) causes. <h3>Methods</h3> This study included 50 patients (Male/Female: 41/9) with VBD and 31 age and gender-matched individuals (Male/Female: 22/9), with DVT associated with non-BD causes. Villalta scale was used to assess of PTS. Venous Disability Score (VDS) and Venous Clinical Severity Score (VCSS) were used for the assessment of venous disease. Venous disease-specific QoL was measured through Venous Insufficiency Epidemiological and Economic Study Quality of Life/Symptom questionnaire (VEINES-QoL/Sym). Behçet Syndrom Activity Score (BSAS) questionnaire was used to assess disease activity. <h3>Results</h3> We observed significantly lower risk of PTS together with significantly better VEINES-QoL, VEINES-Sym and VDS in VBD group compared to NBD group. When VBD patients with PTS were compared to patients without PTS; VEINES-QoL, VEINES-Sym VCSS were significantly worse. BSAS was also significantly higher in patients with PTS. An inverse correlation was found between VEINES-QoL and BSAS in multivariate analysis. There were no differences between anticoagulant users and non-users regarding the presence of PTS and scores of all venous assessment tools. <h3>Conclusions</h3> We found lower PTS risk and better venous disease spesific QoL, symptom severity and venous disability scores in VBD compared to NBD group. Venous disease spesific QoL negatively correlated with disease activity. Effective control of vascular inflammation through treatment in VBD might explain lower PTS and better venous QoL outcomes in VBD patients. Our results suggest that successful control of disease activity might decrease development of PTS, improve venouse disease spesific QoL as well as preventing the relapses in VBD. <h3>Disclosure of Interest</h3> None declared
<i>Notes from the Field</i>: Community-Based Prevention of Rocky Mountain Spotted Fever — Sonora, Mexico, 2016
Authors: Anne Straily, Naomi Drexler, Denica Cruz-Loustaunau, Christopher D. Paddock, Gerardo Alvarez-Hernandez
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Rocky Mountain spotted fever (RMSF), a life-threatening tickborne zoonosis caused by Rickettsia rickettsii, is a reemerging disease in Mexico (1,2). R. rickettsii is an intracellular bacterium that infects vascular endothelium and can cause multisystem organ failure and death in the absence of timely administration of a tetracycline-class antibiotic, typically doxycycline. Epidemic RMSF, as described in parts of Arizona and Mexico, is associated with massive local infestations of the brown dog tick (Rhiphicephalus sanguineus sensu lato) on domestic dogs and in peridomestic settings that result in high rates of human exposure; for example, during 2003-2012, in Arizona the incidence of RMSF in the three most highly affected communities was 150 times the U.S. national average (3,4). In 2015, the Mexico Ministry of Health (MOH) declared an epidemiologic emergency because of high and sustained rates of RMSF in several states in northern Mexico, including the state of Sonora. During 2004-2015, a total of 1,129 cases and 188 RMSF deaths were reported from Sonora (Sonora MOH, unpublished data, 2016). During 2009-2015, one impoverished community (community A) in Sonora reported 56 cases of RMSF involving children and adolescents, with a case-fatality rate of 40% (Sonora MOH, unpublished data, 2016). Poverty and lack of timely access to health services are risk factors for severe RMSF. Children are especially vulnerable to infection, because they might have increased contact with dogs and spend more time playing around spaces where ticks survive (5). In Sonora, case fatality rates for children aged <10 years can be as high as 30%, which is almost four times the aggregate case-fatality rate reported for the general population of the state (8%) (2), and 10-13 times higher than the case-fatality rate described for this age group in the United States (2.4%) (6).
Third-Party Donor Virus-Specific T Cells Are Efficacious in the Treatment of Refractory Viral Infection Following Allogeneic HSCT, but May Not Persist Post-Infusion
Authors: Barbara Withers, Emily Blyth, Leighton Clancy, Jane Burgess, Renee Simms, Kenneth Micklethwaite, David Gottlieb
Journal: Blood (2015)
The Expression of Fas Antigen (CD 95) on Clonogenic Acute Myeloid Leukemia Cells Correlates with Their In Vitro Sensitivity to Farnesyltransferase Inhibitor (FTI; Zarnestra TM).
Authors: Marta Szostek, Edyta Zdzilowska, Aleksander B. Skotnick
Journal: Blood (2004)
Mindfulness-Based Cognitive Therapy in Advanced Prostate Cancer: A Randomized Controlled Trial
Authors: Suzanne K. Chambers, Stefano Occhipinti, Elizabeth Foley, Samantha Clutton, Melissa Legg, Martin Berry, Martin R. Stockler, Mark Frydenberg, Robert A. Gardiner, Stephen J. Lepore, Ian D. Davis, David P. Smith
Journal: Journal of Clinical Oncology (2017)

Purpose Advanced prostate cancer (PC) is associated with substantial psychosocial morbidity. We sought to determine whether mindfulness-based cognitive therapy (MBCT) reduces distress in men with advanced PC. Methods Men with advanced PC (proven metastatic and/or castration-resistant biochemical progression) were randomly assigned to an 8-week, group-based MBCT intervention delivered by telephone (n = 94) or to minimally enhanced usual care (n = 95). Primary intervention outcomes were psychological distress, cancer-specific distress, and prostate-specific antigen anxiety. Mindfulness skills were assessed as potential mediators of effect. Participants were assessed at baseline and were followed up at 3, 6, and 9 months. Main statistical analyses were conducted on the basis of intention to treat. Results Fourteen MBCT groups were conducted in the intervention arm. Facilitator adherence ratings were high (&gt; 93%). Using random-effects mixed-regression models, intention-to-treat analyses indicated no significant changes in intervention outcomes or in engagement with mindfulness for men in MBCT compared with those receiving minimally enhanced usual care. Per-protocol analyses also found no differences between arms in outcomes or engagement, with the exception of the mindfulness skill of observing, which increased over time for men in MBCT compared with usual care ( P = .032). Conclusion MBCT in this format was not more effective than minimally enhanced usual care in reducing distress in men with advanced PC. Future intervention research for these men should consider approaches that map more closely to masculinity.
GP who worked as locum in Cornwall is struck off for inadequate care of three patients
Authors: Clare Dyer
Journal: BMJ (2016)

A German GP who worked as an out-of-hours locum in Cornwall has been struck off the UK medical register for providing inadequate care to three patients in 2013 and 2014.

Klaas Bogena, who had practised for decades as a GP in Bremen, did not attend his hearing at the Medical Practitioners Tribunal Service in Manchester.

But the panel heard in evidence answers that he had given during an investigation by Serco Health—the company that employed him in Cornwall—into his clinical work. Serco’s medical director referred Bogena to the General Medical Council (GMC).

“The tribunal was in no …
Phase I/II Study of Ipilimumab (MDX-010), an Anti-CTLA-4 Monoclonal Antibody, in Patients with Follicular Non-Hodgkin Lymphoma.
Authors: Stephen M. Ansell, Susan M. Geyer, Sara Hurvitz, Donna Fernando, Thomas M. Habermann, David J. Inwards, Meena Verma, Reiko Yamada, John Timmerman
Journal: Blood (2006)
Bone Marrow Biopsy and Aspirate Evaluation in 90 Patients with Essential Thrombocythemia Treated with PEG Interferon alpha-2b. Preliminary Results.
Authors: L. Gugliotta, S. Bulgarelli, A. Tieghi, S. Asioli, G. Gardini, N. Vianelli, A. Candoni, R. Latagliata, S. Rupoli, V. Martinelli, A. Zaccaria, E. De Biasi, S. Sacchi, F. Lauria, M. Miglino, F. Passamonti, A. Tabilio, E. Cacciola, A. Grossi, G. Pisapia, P. Favini, M. Baccarani
Journal: Blood (2004)
浅大腿動脈(SFA)の慢性完全閉塞に対するニチノールステント留置術 多施設登録からの中期臨床成績
Authors: Sakamoto Yasunari, Hirano Keisuke, Muramatsu Toshiya, Ida Osamu, Nanto Shinsuke, Soga Yoshimitsu, Yokoi Hiroyoshi, Nobuyoshi Masakiyo, Suzuki Kenji, Inoue Naoto
Journal: Circulation (2011)
A rapidly acting glutamatergic ARC→PVH satiety circuit postsynaptically regulated by α-MSH
Authors: Henning Fenselau, John N Campbell, Anne M J Verstegen, Joseph C Madara, Jie Xu, Bhavik P Shah, Jon M Resch, Zongfang Yang, Yael Mandelblat-Cerf, Yoav Livneh, Bradford B Lowell
Journal: Nature Neuroscience (2016)
Role Of Hypomethylating Agents For Patients With Lower-Risk Myelodysplastic Syndrome Defined By IPSS and IPSS-R
Authors: Joon Ho Moon, Sang Kyun Sohn, Jae Sook Ahn, Yeo-Kyeoung Kim, Hyeoung Joon Kim, Moo-Kon Song, Ho-Jin Shin, Joo-Seop Chung, Ik Chan Song, Deog-Yeon Jo, Sung Nam Lim, Ho Sup Lee, Yang Soo Kim, Sung Hwa Bae
Journal: Blood (2013)
Comparison of Matched-Sibling Donors Versus Unrelated Donors in Allogeneic Stem Cell Transplantation (allo-SCT) for Primary Refractory Acute Myeloid Leukemia (PRF AML): A Report of 1041 Patients from the Acute Leukemia Working Party of the EBMT
Authors: Eolia Brissot, Myriam Labopin, Matthias Stelljes, Gerhard Ehninger, Gernot Stuhler, Jurgen Finke, Hans Jochem Kolb, Arnold Ganser, Kerstin Schaefer-Eckart, Nicolaus Kroeger, Donald Bunjes, Stephan Mielke, Wolfgang Bethge, Reza Tabrizi, Kalhs Peter, Igor W Blau, Bertran Glass, Antonin Vitek, Martin Gramatzki, Ernst Holler, Christoph Schmid, Jordi Esteve, Arnon Nagler, Mohamad Mohty
Journal: Blood (2015)
FRI0315 A Prospective Study To Assess Responsiveness of Clinical and Ultrasound Outcome Measures for Musculoskeletal Sle: Table 1
Authors: A.S. Zayat, K. Mahmoud, M.Y. Md Yusof, H. Cassamoali, M. D'Agostino, P. Emery, E.M. Vital
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Musculoskeletal manifestations affect up to 95% of SLE patients. Assessment can be problematic as not all patients have swelling. There is a clinical need to better select SLE patients with musculoskeletal symptoms who may respond to therapy and assess their response. We previously analysed 100 patients with MSK symptoms and showed that ultrasound (US) detects synovitis in patients with no clinical swelling. <h3>Objectives</h3> To assess the responsiveness of clinical assessment tools and US in musculoskeletal SLE. <h3>Methods</h3> 107 patients fulfilling ACR/SLICC criteria for SLE with musculoskeletal involvement were analysed in a cross-sectional study. 16 of these with current inflammatory symptoms entered a pilot study of US before and after intramuscular injection of depomedrone 120mg. These 16 patients were followed up and assessed clinically using BILAG, SLEDAI, patient VAS, physician VAS, tender joint count, swollen joint count) and US of hand (joints and tendon sheath) at 0, 2 and 4 weeks. <h3>Results</h3> Of 107 patients only 35 (32.7%) had swelling clinically at baseline but 53 (49.5%) had US synovitis. Response in US and clinical parameters for the 16 longitudinal patients is shown in Table1. <h3>Conclusions</h3> Although swollen joint count was responsive to change with therapy, US was more sensitive in detecting active joints disease at baseline and showed greater and more significant change with therapy. The responsiveness of swollen joints likely explains the responsiveness in BILAG musculoskeletal system index and physician VAS. However, tender and symptomatic joint counts, as well as SLEDAI, were poorly responsive to therapy. Overall, US is the tool most responsive to change for monitoring musculoskeletal disease activity in SLE. <h3>Disclosure of Interest</h3> None declared
Eicosapentaenoic Acid (EPA) Attenuates the Anemia Due to Ribavirin/Interferon a Treatment in Patients with Chronic Hepatitis C.
Authors: Ritsuko Seki, Takashi Okamura, Tatsuya Ide, Toru Maruyama, Takehiko Fujino, Nobuhiro Uyesaka, Michio Sata
Journal: Blood (2004)
AB0031 Evaluation of Serum Fetuin-A and Apelin Levels in Familial Mediterranean Fever (FMF) Patients and Healthy Subjects
Authors: A. Şahin, Ö. Demirpençe, M. Şahin, D. Seven, H.O. Doğan, A. Camcı
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Apelin is an adipokine that its level is increased by some proinflammatory cytokine such as TNF-alpha in metabolic, autoimmune and inflammatory conditions (1). Fetuin-A is protein secreted by liver, kidney, bone, brain, lungs and cardiovascular system (2). The levels of fetuin-a are decreased in some rheumatic diseases (ie. Rheumatoid arthritis, osteoarthritis). It has been suggested that fetuin-a can be a novel inflammatory biomarker in familial Mediterranean fever (FMF) (3). <h3>Objectives</h3> To evaluate of the serum Apelin, Fetuin-A levels in patients with FMF during attack-free period (AFP) and to compare with healthy subjects. <h3>Methods</h3> Thirty-FMF patients with AFP and thirty healthy subjects were included this study. The erythrocyte sedimentation rate (ESR), CRP, fibrinogen, hemogram, Mediterranean fever (MEFV) gene profiles, BMI, insulin, HOMA-IR, lipid profiles, serum apelin, fetuin-a levels were investigated. <h3>Results</h3> Of the FMF patients and control, 20 (66.7%) was female and 10 (33.3%) was male. The distribution of MEFV gene mutation frequencies in the FMF patients was no mutation in 4 (13.3%) patients, M694V heterozygous in 7 (23.3%), M694V homozygous in 3 (10%), E148Q heterozygous in 5 (16.7%), M680I heterozygous in 2 (6.7%), M680I homozygous in 1 (3.3%), V726A in 2 (6.7%) and compound heterozygous mutation in 6 (20%). The median levels of apelin were 307.82±52.76 ng/mL in healthy subjects and 113,07±15,9 ng/mL in FMF (p=0.002) (Figure 1). The median levels of fetuin-a were 843,82±137.66 ng/mL in control group and 1352.2±127.61 ng/mL in FMF group (p=0.009) (Figure 1). <h3>Conclusions</h3> The lower serum apelin and higher fetuin-a levels in FMF patients with AFP than in healthy subjects were observed. It may be suggested that subclinical vascular inflammation is continued during attack-free period in patients with FMF. <h3>References</h3> Andrade-Oliveira V, Camara NO, Moraes-Vieira PM. Adipokines as drug targets in diabetes and underlying disturbances. J Diabetes Res 2015;2015:681612. doi: 10.1155/2015/681612. Epub 2015 Apr 8. Xiao J, Wang XR, Hu KZ, et al. Serum fetuin-A levels are inversely associated with clinical severity in patients with primary knee osteoarthritis. Biomarkers 2013 Feb;18(1):51–4. doi: 10.3109/1354750X.2012.730551. Epub 2012 Oct 16. Oncu K, Yazgan Y, Tanoglu A, et al. Can serum fetuin-A be regarded as an inflammatory marker among patients with familial Mediterranean fever? Dig Dis Sci 2013 Nov;58(11):3212–7. doi: 10.1007/s10620-013-2814-7. Epub 2013 Aug 8. <h3>Acknowledgement</h3> We would like to thank to Ahmet Altun, M.D. for his statistical analysis. <h3>Disclosure of Interest</h3> None declared
Six years without pholcodine; Norwegians are significantly less IgE‐sensitized and clinically more tolerant to neuromuscular blocking agents
Authors: G. H. de Pater, E. Florvaag, S. G. O. Johansson, Å. Irgens, M. N. H. Petersen, A. B. Guttormsen
Journal: Allergy (2016)

As a strong inducer of IgE antibodies to substituted ammonium ion epitopes (QAI), pholcodine (PHO) is a postulated cause of allergic anaphylaxis to neuromuscular blocking agents (NMBAs). Three years after withdrawal of PHO in Norway, a significant reduction in IgE sensitization and anaphylaxis reporting was seen.Six-year follow-up study on the effects of PHO withdrawal on IgE sensitization and anaphylaxis reporting.From 650 acute consecutive reports (2005-2013) to the Norwegian Network for Anaphylaxis under Anaesthesia (NARA), total number of reports on suspected anaphylactic reactions, number of reactions where NMBAs were administered, number of reactions where serum IgE antibodies (≥0.35 kUA /l) to suxamethonium (SUX) and PHO were present at time of reaction and anaphylaxis severity grades were retrieved. In addition, NMBA sales and prevalence of IgE sensitization to PHO and SUX among 'allergics' were monitored.From baseline period P0 (PHO on the market) through the first (P1) and second (P2), three-year periods after withdrawal, significant falls in total reports (P < 0.001) and reports with IgE antibodies to PHO (P = 0.008) and SUX (P = 0.001) at time of reaction were found. Total NMBA sales in P2 were 83% of P0, and SUX and rocuronium (ROC) together made up 86% of sales throughout the study. Five NMBA-related anaphylactic deaths occurred during P0 and P1 and, however, none during P2. Prevalence of IgE sensitization to SUX in 'allergics' fell to 0% at 4 and 5 years after withdrawal.Six years after PHO withdrawal, the Norwegian population has become significantly less IgE-sensitized and clinically more tolerant to NMBAs.
Bone Marrow Connexin-43 Expression Is Critical for Hematopoietic Regeneration after Chemotherapy.
Authors: Andrew W. Lee, Cynthia A. Presley, Bryan D. Kastl, Irogue I. Igbinosa, Yoshiyuki Yamada, Glen I. Fishman, David E. Gutstein, Jose A. Cancelas
Journal: Blood (2005)
P0023 : Comparison of the C3A and HepaRG liver cell lines in monolayer and 3D for bioartificial liver application
Authors: M. Van Wenum, R.A.F.M. Chamuleau, E.J. Hendriks, T.M. van Gulik, A.A.A. Adam, R. Hoekstra
Journal: Journal of Hepatology (2015)
AMC075: The Combination of Vorinostat with Chemotherapy and Rituximab Is Tolerable and Feasible in HIV-Related B-Cell Non-Hodgkin’s Lymphoma with High-Risk Features
Authors: Juan Carlos Ramos, Joseph Sparano, Page Moore, Jeannette Y. Lee, Michelle A Rudek, Richard F. Ambinder, Ethel Cesarman, Ariela Noy, Ronald T. Mitsuyasu
Journal: Blood (2014)
Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia
Authors: Ling-Wen Ding, Qiao-Yang Sun, Kar-Tong Tan, Wenwen Chien, Anand Mayakonda Thippeswamy, Allen Eng Juh Yeoh, Norihiko Kawamata, Yasunobu Nagata, Jin-Fen Xiao, Xin-Yi Loh, De-Chen Lin, Manoj Garg, Yan-Yi Jiang, Liang Xu, Su-Lin Lim, Li-Zhen Liu, Vikas Madan, Masashi Sanada, Lucia Torres Fernández, Hema Preethi, Michael Lill, Hagop M. Kantarjian, Steven M. Kornblau, Satoru Miyano, Der-Cherng Liang, Seishi Ogawa, Lee-Yung Shih, Henry Yang, H. Phillip Koeffler
Journal: Cancer Research (2016)

Abstract Current standard of care for patients with pediatric acute lymphoblastic leukemia (ALL) is mainly effective, with high remission rates after treatment. However, the genetic perturbations that give rise to this disease remain largely undefined, limiting the ability to address resistant tumors or develop less toxic targeted therapies. Here, we report the use of next-generation sequencing to interrogate the genetic and pathogenic mechanisms of 240 pediatric ALL cases with their matched remission samples. Commonly mutated genes fell into several categories, including RAS/receptor tyrosine kinases, epigenetic regulators, transcription factors involved in lineage commitment, and the p53/cell-cycle pathway. Unique recurrent mutational hotspots were observed in epigenetic regulators CREBBP (R1446C/H), WHSC1 (E1099K), and the tyrosine kinase FLT3 (K663R, N676K). The mutant WHSC1 was established as a gain-of-function oncogene, while the epigenetic regulator ARID1A and transcription factor CTCF were functionally identified as potential tumor suppressors. Analysis of 28 diagnosis/relapse trio patients plus 10 relapse cases revealed four evolutionary paths and uncovered the ordering of acquisition of mutations in these patients. This study provides a detailed mutational portrait of pediatric ALL and gives insights into the molecular pathogenesis of this disease. Cancer Res; 77(2); 390–400. ©2016 AACR.