H2.0-like Homeobox Regulates Early Hematopoiesis and Promotes Acute Myeloid Leukemia

Masahiro Kawahara, Ashley Pandolfi, Boris Bartholdy, Laura Barreyro, Britta Will, Michael Roth, Ujunwa C. Okoye-Okafor, Tihomira I. Todorova, Maria E. Figueroa, Ari Melnick, Constantine S. Mitsiades, Ulrich Steidl

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Homeobox domain-containing transcription factors are important regulators of hematopoiesis. Here, we report that increased levels of nonclustered H2.0-like homeobox (HLX) lead to loss of functional hematopoietic stem cells and formation of aberrant progenitors with unlimited serial clonogenicity and blocked differentiation. Inhibition of HLX reduces proliferation and clonogenicity of leukemia cells, overcomes the differentiation block, and leads to prolonged survival. HLX regulates a transcriptional program, including PAK1 and BTG1, that controls cellular differentiation and proliferation. HLX is overexpressed in 87% of patients with acute myeloid leukemia (AML) and independently correlates with inferior overall survival (n = 601, p = 2.3 × 10 -6). Our study identifies HLX as a key regulator in immature hematopoietic and leukemia cells and as a prognostic marker and therapeutic target in AML.

Original languageEnglish (US)
Pages (from-to)194-208
Number of pages15
JournalCancer Cell
Volume22
Issue number2
DOIs
StatePublished - Aug 14 2012

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Kawahara, M., Pandolfi, A., Bartholdy, B., Barreyro, L., Will, B., Roth, M., Okoye-Okafor, U. C., Todorova, T. I., Figueroa, M. E., Melnick, A., Mitsiades, C. S., & Steidl, U. (2012). H2.0-like Homeobox Regulates Early Hematopoiesis and Promotes Acute Myeloid Leukemia. Cancer Cell, 22(2), 194-208. https://doi.org/10.1016/j.ccr.2012.06.027