Driver Mutations in Leukemia Promote Disease Pathogenesis through a Combination of Cell-Autonomous and Niche Modulation

dc.contributor.authorRamdas, Baskar
dc.contributor.authorMali, Raghuveer Singh
dc.contributor.authorPalam, Lakshmi Reddy
dc.contributor.authorPandey, Ruchi
dc.contributor.authorCai, Zhigang
dc.contributor.authorPasupuleti, Santhosh Kumar
dc.contributor.authorBurns, Sarah S.
dc.contributor.authorKapur, Reuben
dc.contributor.departmentPediatrics, School of Medicineen_US
dc.date.accessioned2020-11-25T16:01:22Z
dc.date.available2020-11-25T16:01:22Z
dc.date.issued2020-07-14
dc.description.abstractStudies of patients with acute myeloid leukemia (AML) have led to the identification of mutations that affect different cellular pathways. Some of these have been classified as preleukemic, and a stepwise evolution program whereby cells acquire additional mutations has been proposed in the development of AML. How the timing of acquisition of these mutations and their impact on transformation and the bone marrow (BM) microenvironment occurs has only recently begun to be investigated. We show that constitutive and early loss of the epigenetic regulator, TET2, when combined with constitutive activation of FLT3, results in transformation of chronic myelomonocytic leukemia-like or myeloproliferative neoplasm-like phenotype to AML, which is more pronounced in double-mutant mice relative to mice carrying mutations in single genes. Furthermore, we show that in preleukemic and leukemic mice there are alterations in the BM niche and secreted cytokines, which creates a permissive environment for the growth of mutation-bearing cells relative to normal cells.en_US
dc.identifier.citationRamdas, B., Mali, R. S., Palam, L. R., Pandey, R., Cai, Z., Pasupuleti, S. K., Burns, S. S., & Kapur, R. (2020). Driver Mutations in Leukemia Promote Disease Pathogenesis through a Combination of Cell-Autonomous and Niche Modulation. Stem Cell Reports, 15(1), 95–109. https://doi.org/10.1016/j.stemcr.2020.05.002en_US
dc.identifier.issn2213-6711en_US
dc.identifier.urihttps://hdl.handle.net/1805/24471
dc.language.isoen_USen_US
dc.publisherElsevieren_US
dc.relation.isversionof10.1016/j.stemcr.2020.05.002en_US
dc.relation.journalStem Cell Reportsen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0*
dc.sourcePMCen_US
dc.subjectTET2en_US
dc.subjectFlt3ITD/ITDen_US
dc.subjectbone marrow microenvironmenten_US
dc.subjectAMLen_US
dc.subjectCMMLen_US
dc.subjectMPNen_US
dc.subjectcytokinesen_US
dc.titleDriver Mutations in Leukemia Promote Disease Pathogenesis through a Combination of Cell-Autonomous and Niche Modulationen_US
dc.typeArticleen_US
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