Reprogramming of primary human Philadelphia chromosome-positive B cell acute lymphoblastic leukemia cells into nonleukemic macrophages

Proceedings of the National Academy of Sciences of the United States of America
James Scott McClellanRavindra Majeti

Abstract

BCR-ABL1(+) precursor B-cell acute lymphoblastic leukemia (BCR-ABL1(+) B-ALL) is an aggressive hematopoietic neoplasm characterized by a block in differentiation due in part to the somatic loss of transcription factors required for B-cell development. We hypothesized that overcoming this differentiation block by forcing cells to reprogram to the myeloid lineage would reduce the leukemogenicity of these cells. We found that primary human BCR-ABL1(+) B-ALL cells could be induced to reprogram into macrophage-like cells by exposure to myeloid differentiation-promoting cytokines in vitro or by transient expression of the myeloid transcription factor C/EBPα or PU.1. The resultant cells were clonally related to the primary leukemic blasts but resembled normal macrophages in appearance, immunophenotype, gene expression, and function. Most importantly, these macrophage-like cells were unable to establish disease in xenograft hosts, indicating that lineage reprogramming eliminates the leukemogenicity of BCR-ABL1(+) B-ALL cells, and suggesting a previously unidentified therapeutic strategy for this disease. Finally, we determined that myeloid reprogramming may occur to some degree in human patients by identifying primary CD14(+) monocytes...Continue Reading

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Citations

Jun 13, 2015·Proceedings of the National Academy of Sciences of the United States of America·Ravindra MajetiJames Scott McClellan
Jun 13, 2015·Proceedings of the National Academy of Sciences of the United States of America·Karel FišerEster Mejstříková
Jun 3, 2015·Journal of Molecular Cell Biology·Grigori SingovskiAriel Ruiz I Altaba
May 29, 2016·Chinese Journal of Cancer·Zhi-Jie KangQuentin Liu
Jun 22, 2016·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Kwang-Hyun ChoSang-Min Park
Jul 9, 2016·Stem Cells Translational Medicine·Kiran BattaValerie Kouskoff
Feb 18, 2017·Reports on Progress in Physics·Ruoshi YuanPing Ao
Sep 22, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Renato BassanSabina Chiaretti
Aug 30, 2019·Cancer Communications·Lanqi GongXinyuan Guan
Dec 6, 2019·Oncogene·Alexandre Teixeira VessoniLuis Francisco Zirnberger Batista
Mar 12, 2020·Stem Cells·Huafeng Xie, Thomas Graf
Dec 4, 2016·Genes & Development·Rajesh SomasundaramMikael Sigvardsson
Nov 23, 2017·Frontiers in Oncology·Tianyuan HuDaisuke Nakada
May 19, 2018·International Journal of Molecular Sciences·Inés González-HerreroCarolina Vicente-Dueñas
Oct 22, 2016·BMC Systems Biology·Sung-Hwan ChoKwang-Hyun Cho
Jun 6, 2018·Frontiers in Oncology·Lan V PhamRichard J Ford
Jul 25, 2021·Cancers·Emanuele CenciniMonica Bocchia
Aug 10, 2021·Frontiers in Immunology·Olga ZimmermannovaCarlos-Filipe Pereira

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