Hoxa9 and Hoxa10 induce CML myeloid blast crisis development through activation of Myb expression.

ABSTRACT: Mechanisms underlying the progression of Chronic Myeloid Leukemia (CML) from chronic phase to myeloid blast crisis are poorly understood. Our previous studies have suggested that overexpression of SETBP1 can drive this progression by conferring unlimited self-renewal capability to granulocyte macrophage progenitors (GMPs). Here we show that overexpression of Hoxa9 or Hoxa10, both transcriptional targets of Setbp1, is also sufficient to induce self-renewal of primary myeloid progenitors, causing their immortalization in culture. More importantly, both are able to cooperate with BCR/ABL to consistently induce transformation of mouse GMPs and development of aggressive leukemias resembling CML myeloid blast crisis, suggesting that either gene can drive CML pr

SUBMITTER: Negi V 

PROVIDER: S-EPMC5716772 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature