TitleH2.0-like homeobox regulates early hematopoiesis and promotes acute myeloid leukemia.
Publication TypeJournal Article
Year of Publication2012
AuthorsKawahara, Masahiro, Pandolfi Ashley, Bartholdy Boris, Barreyro Laura, Will Britta, Roth Michael, Okoye-Okafor Ujunwa C., Todorova Tihomira I., Figueroa Maria E., Melnick Ari, Mitsiades Constantine S., and Steidl Ulrich
JournalCancer Cell
Date Published2012 Aug 14
KeywordsAnimals, Antigens, CD34, Cell Cycle, Cell Death, Cell Differentiation, Clone Cells, Down-Regulation, Flow Cytometry, Gene Expression Regulation, Neoplastic, Hematopoiesis, Hematopoietic Stem Cells, Homeodomain Proteins, Humans, Lentivirus, Leukemia, Myeloid, Acute, Mice, Monocytes, Proto-Oncogene Proteins c-kit, Survival Analysis, Transcription Factors, Transcriptome

<p>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.</p>

Alternate JournalCancer Cell
PubMed ID22897850
PubMed Central IDPMC3422691
Grant ListR01 CA166429 / CA / NCI NIH HHS / United States
R00CA131503 / CA / NCI NIH HHS / United States
F30 HL117545 / HL / NHLBI NIH HHS / United States
T32 GM007288 / GM / NIGMS NIH HHS / United States
R00 CA131503 / CA / NCI NIH HHS / United States