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

ASXL2 regulates hematopoiesis in mice and its deficiency promotes myeloid expansion. Haematologica. 2018 Aug 09;: Authors: Madan V, Han L, Hattori N, Teoh WW, Mayakonda A, Sun QY, Ding LW, Binte Mohd Nordin H, Lim SL, Shyamsunder P, Dakle P, Sundaresan J, Doan NB, Sanada M, Sato-Otsubo A, Meggendorfer M, Yang H, Said JW, Ogawa S, Haferlach T, Liang DC, Shih LY, Nakamaki T, Wang QT, Koeffler HP Abstract Chromosomal translocation t(8;21)(q22;q22) which leads to generation of oncogenic RUNX1-RUNX1T1 (AML1-ETO) fusion is observed in about 10% of acute myelogenous leukemia (AML). To uncover somatic mutations that cooperate 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...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research