TY - JOUR
T1 - H2.0-like Homeobox Regulates Early Hematopoiesis and Promotes Acute Myeloid Leukemia
AU - Kawahara, Masahiro
AU - Pandolfi, Ashley
AU - Bartholdy, Boris
AU - Barreyro, Laura
AU - Will, Britta
AU - Roth, Michael
AU - Okoye-Okafor, Ujunwa C.
AU - Todorova, Tihomira I.
AU - Figueroa, Maria E.
AU - Melnick, Ari
AU - Mitsiades, Constantine S.
AU - Steidl, Ulrich
N1 - Funding Information:
We thank the Einstein Human Stem Cell FACS and Xenotransplantation Facility for expert technical assistance (supported by NYSTEM Grant no. C024172). This work was supported by a new investigator award of the Leukemia Research Foundation, an investigator-initiated research project of NYSTEM (Grant no. CO24350), a Howard Temin Award of the National Cancer Institute (Grant no. R00CA131503), and a Medical Research Award of the Gabrielle’s Angel Foundation for Cancer Research (to U.S.). U.S. is the Diane and Arthur B. Belfer Faculty Scholar in Cancer Research of the Albert Einstein College of Medicine.
PY - 2012/8/14
Y1 - 2012/8/14
N2 - 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.
AB - 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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U2 - 10.1016/j.ccr.2012.06.027
DO - 10.1016/j.ccr.2012.06.027
M3 - Article
C2 - 22897850
AN - SCOPUS:84865132216
SN - 1535-6108
VL - 22
SP - 194
EP - 208
JO - Cancer Cell
JF - Cancer Cell
IS - 2
ER -