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XB-ART-52805
Oncotarget. December 27, 2016; 7 (52): 86889-86901.

VENTX induces expansion of primitive erythroid cells and contributes to the development of acute myeloid leukemia in mice.

Gentner E , Vegi NM , Mulaw MA , Mandal T , Bamezai S , Claus R , Tasdogan A , Quintanilla-Martinez L , Grunenberg A , Döhner K , Döhner H , Bullinger L , Haferlach T , Buske C , Rawat VP , Feuring-Buske M .


Abstract
Homeobox genes are key regulators in normal and malignant hematopoiesis. The human Vent-like homeobox gene VENTX, a putative homolog of the Xenopus laevis Xvent-2 gene, was shown to be highly expressed in normal myeloid cells and in patients with acute myeloid leukemia. We now demonstrate that constitutive expression of VENTX suppresses expression of genes responsible for terminal erythroid differentiation in normal CD34+ stem and progenitor cells. Transplantation of bone marrow progenitor cells retrovirally engineered to express VENTX caused massive expansion of primitive erythroid cells and partly acute erythroleukemia in transplanted mice. The leukemogenic potential of VENTX was confirmed in the AML1-ETO transplantation model, as in contrast to AML1-ETO alone co-expression of AML1-ETO and VENTX induced acute myeloid leukemia, partly expressing erythroid markers, in all transplanted mice. VENTX was highly expressed in patients with primary human erythroleukemias and knockdown of VENTX in the erythroleukemic HEL cell line significantly blocked cell growth. In summary, these data indicate that VENTX is able to perturb erythroid differentiation and to contribute to myeloid leukemogenesis when co-expressed with appropriate AML oncogenes and point to its potential significance as a novel therapeutic target in AML.

PubMed ID: 27888632
PMC ID: PMC5349961
Article link: Oncotarget.

Genes referenced: gnl3 ptpn11 runx1


References:
Abramovich, 2005, Pubmed[+]


Article Images: [+] show captions

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