Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/212676
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dc.titleRETENTION OF RUNX1-INSUFFICIENT CD41+ PLATELET-BIASED HEMATOPOIETIC STEM CELLS IN NICHE BY ADDITIONAL GENETIC MUTATIONS FACILITATES MYELOID LEUKEMOGENESIS
dc.contributor.authorMOK MENG HUANG, MICHELLE
dc.date.accessioned2021-12-31T18:00:27Z
dc.date.available2021-12-31T18:00:27Z
dc.date.issued2021-07-03
dc.identifier.citationMOK MENG HUANG, MICHELLE (2021-07-03). RETENTION OF RUNX1-INSUFFICIENT CD41+ PLATELET-BIASED HEMATOPOIETIC STEM CELLS IN NICHE BY ADDITIONAL GENETIC MUTATIONS FACILITATES MYELOID LEUKEMOGENESIS. ScholarBank@NUS Repository.
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/212676
dc.description.abstractRUNX1 is among the most frequently mutated genes in human myeloid leukemia. RUNX1 alterations per se, though being leukemia-prone, are insufficient to cause overt leukemia due to a niche interaction defect. Additional genetic changes in NRAS and MLL5 have been observed in RUNX1 leukemia, yet the molecular basis for this synergism remains elusive. Here we report that restoration of niche interaction of HSCs is facilitated by such additional genetic changes in myeloid leukemogenesis. Flow cytometry analysis demonstrated that concurrent genetic alterations lead to the propagation of CD41+ platelet-biased HSCs which may serve as a cell-of-origin for myeloid leukemia. Mechanistically, transcriptional repression of DNA damage-inducing LINE-1 retrotransposon by Runx1 and CTCF-Stat5 mediated by niche-derived thrombopoietin is attenuated in the Runx1 mutant HSCs, but restored by the acquisition of the second hits. These findings on the niche-related mechanism would provide deeper insights into myeloid leukemogenesis and may lead to novel therapeutics.
dc.language.isoen
dc.subjectCD41, MEGAKARYOCYTE-BIAS, HEMATOPOIETIC STEM CELLS, LEUKEMIA, RUNX1
dc.typeThesis
dc.contributor.departmentDEAN'S OFFICE (MEDICINE)
dc.contributor.supervisorChng Wee Joo
dc.contributor.supervisorOsato, Motomi
dc.description.degreePh.D
dc.description.degreeconferredDOCTOR OF PHILOSOPHY (SOM)
dc.identifier.orcid0000-0001-7030-266X
Appears in Collections:Ph.D Theses (Restricted)

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