Journal article
Single-cell panleukemia signatures of HSPC-like blasts predict drug response and clinical outcome
Blood, v 145(23)
16 Mar 2025
PMID: 40089994
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The critical role of leukemic initiating cells as a therapy-resistant population in myeloid leukemia is well established, however, the molecular signatures of such cells in acute lymphoblastic leukemia remain underexplored. Moreover, their role in therapy response and patient prognosis is yet to be systematically investigated across various types of acute leukemia. We employed single-cell multiomics to analyze diagnostic specimens from 96 pediatric patients with acute lymphoblastic, myeloid, and lineage ambiguous leukemias. Through the integration of single-cell multiomics with extensive bulk RNA-Seq and clinical datasets, we uncovered a prevalent, chemotherapy-resistant subpopulation that resembles hematopoietic stem and progenitor cells (HSPC-like) and is associated with poor clinical outcomes across all subtypes investigated. We identified a core transcriptional regulatory network (TRN) in HSPC-like blasts that is combinatorically controlled by HOXA/AP1/CEBPA. This TRN signature can predict chemotherapy response and long-term clinical outcomes. We identified shared potential therapeutic targets against HSPC-like blasts, including FLT3, BCL2, and the PI3K pathway. Our study provides a framework for linking intra-tumoral heterogeneity with therapy response, patient outcome and discovery of new therapeutic targets for pediatric acute leukemias.
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Details
- Title
- Single-cell panleukemia signatures of HSPC-like blasts predict drug response and clinical outcome
- Creators
- Changya Chen - Institute of Hematology & Blood Diseases HospitalJason Xu - University of PennsylvaniaJonathan H Sussman - University of PennsylvaniaTiffaney L Vincent - Children's Hospital of PhiladelphiaJoseph S Tumulty - Children's Hospital of PhiladelphiaSatoshi Yoshimura - St. Jude Children's Research HospitalFatemeh Alikarami - Children's Hospital of PhiladelphiaWenbao Yu - Children's Hospital of PhiladelphiaYang-Yang Ding - Johns Hopkins University School of MedicineChia-Hui Chen - Children's Hospital of PhiladelphiaElizabeth Y Li - Children's Hospital of PhiladelphiaAustin Yang - University of PennsylvaniaXiaohuan Qin - Chinese Academy of Medical Sciences & Peking Union Medical CollegeShovik Bandyopadhyay - University of PennsylvaniaJacqueline Jiahui Peng - University of PennsylvaniaPetri Pölönen - St. Jude Children's Research HospitalHaley Newman - Children's Hospital of PhiladelphiaBrent Wood - Children's Hospital of Los AngelesJianzhong Hu - St. Jude Children's Research HospitalRawan Shraim - Children's Hospital of PhiladelphiaAndrew D Hughes - Children's Hospital of PhiladelphiaCaroline Diorio - Children's Hospital of PhiladelphiaLahari Uppuluri - Children's Hospital of PhiladelphiaGongping Shi - Children's Hospital of PhiladelphiaTheresa Ryan - Children's Hospital of PhiladelphiaTori Fuller - Children's Hospital of PhiladelphiaMignon L Loh - Seattle Children's HospitalElizabeth A Raetz - New York UniversityStephen P Hunger - Children's Hospital of PhiladelphiaStanley B Pounds - St. Jude Children's Research HospitalCharles G Mullighan - St. Jude Children's Research HospitalDavid Frank - Children's Hospital of PhiladelphiaJun J Yang - St. Jude Children's Research HospitalKathrin Maria Bernt - Children's Hospital of PhiladelphiaDavid Trent Teachey - Children's Hospital of PhiladelphiaKai Tan - Children's Hospital of Philadelphia
- Publication Details
- Blood, v 145(23)
- Publisher
- ELSEVIER; AMSTERDAM
- Number of pages
- 16
- Grant note
- K12 CA076931 / NCI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:001507216900002
- Scopus ID
- 2-s2.0-105003954688
- Other Identifier
- 991022041191604721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Hematology