Dataset Information

ASXL2 regulates hematopoiesis in mice and its deficiency promotes myeloid expansion.

ABSTRACT: Chromosomal translocation t(8;21)(q22;q22) which leads to the generation of oncogenic RUNX1-RUNX1T1 (AML1-ETO) fusion is observed in approximately 10% of acute myelogenous leukemia (AML). To identify somatic mutations that co-operate with t(8;21)-driven leukemia, we performed whole and targeted exome sequencing of an Asian cohort at diagnosis and relapse. We identified high frequency of truncating alterations in ASXL2 along with recurrent mutations of KIT, TET2, MGA, FLT3, and DHX15 in this subtype of AML. To investigate in depth the role of ASXL2 in normal hematopoiesis, we utilized a mouse model of ASXL2 deficiency. Loss of ASXL2 caused progressive hematopoietic defects characterized by myeloid hyperplasia, splenomegaly, extramedullary hematopoiesis, and poor reconstitution ability in transplantation models. Parallel analyses of young and >1-year old Asxl2-deficient mice revealed age-dependent perturbations affecting, not only myeloid and erythroid differentiation, but also maturation of lymphoid cells. Overall, these findings establish a critical role for ASXL2 in maintaining steady state hematopoiesis, and provide insights into how its loss primes the expansion of myeloid cells.

SUBMITTER: Madan V

PROVIDER: S-EPMC6269306 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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ASXL2 regulates hematopoiesis in mice and its deficiency promotes myeloid expansion.

Madan Vikas V Han Lin L Hattori Norimichi N Teoh Weoi Woon WW Mayakonda Anand A Sun Qiao-Yang QY Ding Ling-Wen LW Nordin Hazimah Binte Mohd HBM Lim Su Lin SL Shyamsunder Pavithra P Dakle Pushkar P Sundaresan Janani J Doan Ngan B NB Sanada Masashi M Sato-Otsubo Aiko A Meggendorfer Manja M Yang Henry H Said Jonathan W JW Ogawa Seishi S Haferlach Torsten T Liang Der-Cherng DC Shih Lee-Yung LY Nakamaki Tsuyoshi T Wang Q Tian QT Koeffler H Phillip HP

Haematologica 20180809 12

Chromosomal translocation t(8;21)(q22;q22) which leads to the generation of oncogenic RUNX1-RUNX1T1 (AML1-ETO) fusion is observed in approximately 10% of acute myelogenous leukemia (AML). To identify somatic mutations that co-operate with t(8;21)-driven leukemia, we performed whole and targeted exome sequencing of an Asian cohort at diagnosis and relapse. We identified high frequency of truncating alterations in ASXL2 along with recurrent mutations of KIT, TET2, MGA, FLT3, and D ...[more]

PMID: 30093396

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ASXL2 regulates hematopoiesis in mice and its deficiency promotes myeloid expansion.

Publications

ASXL2 regulates hematopoiesis in mice and its deficiency promotes myeloid expansion.

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