Hhex induces promyelocyte self-renewal and cooperates with growth factor independence to cause myeloid leukemia in mice

JT Jackson; AP Ng; BJ Shields; S Haupt; Y Haupt; MP McCormack

Journal article

Hhex induces promyelocyte self-renewal and cooperates with growth factor independence to cause myeloid leukemia in mice

JT Jackson, AP Ng, BJ Shields, S Haupt, Y Haupt, MP McCormack

Blood Advances | AMER SOC HEMATOLOGY | Published : 2018

DOI: 10.1182/bloodadvances.2017013243

Abstract

The hematopoietically expressed homeobox (Hhex) transcription factor is overexpressed in humanmyeloid leukemias. Conditional knockoutmodels ofmurine acutemyeloid leukemia indicate that Hhexmaintains leukemia stemcell self-renewal by enabling Polycomb-mediated epigenetic repression of the Cdkn2a tumor suppressor locus, encoding p16Ink4a and p19Arf. However, whether Hhex overexpression also affects hematopoietic differentiation is unknown. To study this, we retrovirally overexpressed Hhex in hematopoietic progenitors. This enabled serial replating of myeloid progenitors, leading to the rapid establishment of interleukin-3 (IL-3)-dependent promyelocytic cell lines. Use of a Hhex-ERT2 fusion pro..

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University of Melbourne Researchers

Ashley Ng Author

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RESEARCH FELLOWSHIP - PROF CHRISTOS PANTELIS

I have established and head the Melbourne Neuropsychiatry Centre within the University of Melbourne. My university position is a research ch..

Grants

Funding Acknowledgements

This work was supported by project grants (628386, 1003391 [M.P.M.], 1126772 [B.J.S. and M.P.M.]) and the Independent Research Institute's Infrastructure Support Scheme from the Australian Government's National Health and Medical Research Council, a Future Fellowship from the Australian Research Council (M.P.M.), and a Victorian State Government Operational Infrastructure Support grant.