[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-455699-105":3,"detail-sidebar-cat-0-en-105":80,"doc-detail-455699-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":73,"head_meta":75,"extra_data":77,"updated_unix":79},105,"en","cell-state-transitions-drive-the-evolution-of-disease-progression-in-b-lymphoblastic-leukemia","Cell State Transitions Drive the Evolution of Disease Progression in B-Lymphoblastic Leukemia","","Cancer stem cells (CSCs) are proposed to accelerate tumor progression through innate chemoresistance and self-renewal. A key challenge is isolating CSCs from B-lymphoblastic leukemia (B-ALL), motivating a model of temporal, stochastic cell state transitions driven by changing CD34 and CD38 expression. The study links transition rates with BCR::ABL1 status, minimal residual disease (MRD), and relapse in adult B-ALL. Results suggest dedifferentiating transitions into a CD34+/CD38− stem-like phenotype, with therapy simulations indicating that blocking entry to this state reduces the stem-like population more effectively than promoting differentiation.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/cell-state-transitions-drive-the-evolution-of-disease-progression-in-b-lymphoblastic-leukemia/455699/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/cell-state-transitions-drive-the-evolution-of-disease-progression-in-b-lymphoblastic-leukemia/455699.png","ImageObject",300,407,{"name":42,"@type":43},"Rowan","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-06","2026-09-30",true,{"@type":52,"interactionType":53,"userInteractionCount":33},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58,64,68],{"name":59,"@type":60,"acceptedAnswer":61},"Why is isolating cancer stem cells from B-ALL difficult?","Question",{"text":62,"@type":63},"CSC-like cells in B-ALL are not confined to a single CD34+/CD38− compartment. The paper suggests temporal changes in CD34 and CD38 can produce stochastic transitions between immunophenotypic states.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"What factors are correlated with the modeled cell state transitions?",{"text":67,"@type":63},"The model findings are correlated with BCR::ABL1 status, minimal residual disease (MRD), and relapse outcomes in adult B-ALL.",{"name":69,"@type":60,"acceptedAnswer":70},"How do therapy simulations affect the CD34+/CD38− stem-like population?",{"text":71,"@type":63},"Simulated therapies targeting the stem-like compartment indicate that blocking transitions into the CD34+/CD38− state (dedifferentiation) is more effective than promoting transitions out of that state (differentiation) for reducing the CD34+/CD38− proportion.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},455699,1790840247,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,109,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":88,"show_sort_weight":89,"slug":90},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":92,"show_sort_weight":93,"slug":94},"Exam",70,"exam",{"id":96,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},5,"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":107,"slug":108},7,40,"healthcare",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},8,"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":96,"slug":129},19,"General","general",{"code":4,"msg":81,"data":131},{"doc_id":78,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":106,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":33,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},1099514067415,"https://ap-avatar.wpscdn.com/avatar/100002539d78ffe74a7?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779092875211072502","RESEARCH ARTICLE  [https://doi.org/10.1158/2767-9764.CRC-25-0277](https://doi.org/10.1158/2767-9764.CRC-25-0277)  OPEN ACCESS  \nCell State Transitions Drive the Evolution of Disease Progression in B-Lymphoblastic Leukemia  \nCurtis Gravenmier1, Sadegh Marzban2, Yi-Han Tang3, Nancy Gillis3,4, Bijal D. Shah4, Lynn C. Moscinski1, Ling Zhang1, and Jeffrey West2  \n􀀶  \nABSTRACT  \nCancer stem cells (CSC) are hypothesized to promote tumor progression through innate chemoresistance and self-renewal. CSCs reside in the CD34+/CD38 􀀁 immunophenotypic subpopulation of acute myeloid leukemia (AML) . Isolation of CSCs from B-lymphoblastic leukemia (B-ALL) has proven difficult, and the cells of interest apparently are not isolated to the CD34+/CD38 􀀁 compartment. This may be explained, in part, by temporal variations of CD34 and CD38 expression which result in stochastic cell state transitions (e.g., from CD34+/CD38+ to CD34+/ CD38 􀀁 ) . We present a mathematical model of these transitions and correlate salient findings with BCR::ABL1 status, minimal residual disease (MRD), and relapse in adult B-ALL. As the CSC hypothesis is well supported in AML, we focus on transitions to and from the hematopoietic stem cell compartment (CD34+/CD38 􀀁 ) . Our analysis suggests the presence of dedifferentiating transitions to a CD34+/CD38 􀀁 stem cell–like immunophenotype, especially in B-ALL with BCR::ABL1 . In contrast, BCR::ABL1-negative patient samples have low CD34+/CD38 􀀁  \nself-renewal rates and either high CD34+/CD38+ or CD34 􀀁 /CD38+ incoming rates. High CD34+/CD38 􀀁 self-renewal is also associated with positive MRD following induction chemotherapy. We find a lack of observable changes in cell state transitions between diagnosis and relapse specimens. Furthermore, simulated therapies targeting the stem cell–like compartment indicate that blocking transitions to the CD34+/CD38 􀀁 state (i.e., blocking dedifferentiation) is more effective than promoting transitions from the CD34+/CD38 􀀁 state toward other states (i.e., promoting differentiation) to reduce the proportion of CD34+/ CD38 􀀁 cells. The modeling framework used here is a novel, useful tool to infer prognosis and genotype from routine flow cytometry.  \nSignificance: Flow cytometry characterization of B-ALL samples (diagnosis, remission, and relapse) is used to parameterize a mathematical model of cell state transition rates and stratify patients for post-induction chemotherapy MRD.  \nIntroduction  \nCancer stem cells (CSC) are hypothesized to drive tumor progression by serving as a drug-resistant reservoir with the capacity for self-renewal. The first empirical evidence to support CSCs was obtained from human acute myeloid leukemia (AML) when it was discovered that the ability to  \n1Hematopathology and Laboratory Medicine, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida. 2Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida. 3Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida. 4Department of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.  \nC. Gravenmier and S. Marzban contributed equally to this article.  \nL. Zhang and J. West are co-senior authors of this article.  \nCorresponding Authors: Ling Zhang, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, [FL 33612. E-mail:](FL 33612. E-mail: Ling.Zhang@moffitt.org)[ Ling.Zhang@moffitt.org](FL 33612. E-mail: Ling.Zhang@moffitt.org); and Jeffrey West, [Jeffrey.West@moffitt.org](Jeffrey.West@moffitt.org)  \ndoi: 10.1158/2767-9764.CRC-25-0277  \nThis open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license.  \n©2025 The Authors; Published by the American Association for Cancer Research  \ntransplant AML to severe combined immune-deficient mice is restricted to leukemia cells with a CD34+/CD38 􀀁 immunophenotype similar to normal hematopoietic st","cbCaiondDskC8Gvt","https://ap.wps.com/l/cbCaiondDskC8Gvt","pdf",15518428,13,"English","# Abstract\n# Introduction\n## Cancer stem cells and drug resistance\n## CD34/CD38 immunophenotype dynamics\n## Modeling transitions and clinical correlations","[{\"question\":\"Why is isolating cancer stem cells from B-ALL difficult?\",\"answer\":\"CSC-like cells in B-ALL are not confined to a single CD34+/CD38− compartment. The paper suggests temporal changes in CD34 and CD38 can produce stochastic transitions between immunophenotypic states.\"},{\"question\":\"What factors are correlated with the modeled cell state transitions?\",\"answer\":\"The model findings are correlated with BCR::ABL1 status, minimal residual disease (MRD), and relapse outcomes in adult B-ALL.\"},{\"question\":\"How do therapy simulations affect the CD34+/CD38− stem-like population?\",\"answer\":\"Simulated therapies targeting the stem-like compartment indicate that blocking transitions into the CD34+/CD38− state (dedifferentiation) is more effective than promoting transitions out of that state (differentiation) for reducing the CD34+/CD38− proportion.\"}]","Cell State Transitions Drive the Evolution of Disease Progression in B-Lymphoblastic Leukemia | PDF",1790743903,33]