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

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2012 Aug 18

PMID 22897850

Citations 32

Authors

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

Affiliations

Soon will be listed here.

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.

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