HOXA9 Gene Expression in Acute Myeloid Leukemia

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ORIGINAL PAPER

HOXA9 Gene Expression in Acute Myeloid Leukemia De-Peng Li • Zhen-Yu Li • Wei Sang • Hai Cheng • Xiu-Ying Pan • Kai-Lin Xu

Ó Springer Science+Business Media New York 2013

Abstract Homeobox genes encode the class of transcription factors in vertebrates and are found in clusters called A, B, C, and D on four separate chromosomes. HOXA9 gene is part of the cluster A on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. The objective of this study was to determine the HOXA9 gene expression in acute myeloid leukemia (AML). For this purpose, semi-quantitative reverse transcriptase-polymerase chain reaction was used to measure HOXA9 gene expression in human erythroleukemia (HEL) cell line and bone marrow mononuclear cells from 54 AML patients and 20 healthy individuals. The data show that HOXA9 mRNA expression was negative in 20 healthy individuals but was positive in HEL cells and in 22 out of 54 (40.74 %) AML patients. The complete remission rate (45.45 %) of the patients who expressed the gene was significantly lower than that (71.86 %) in patients who did not express the gene after chemotherapy. Therefore, it was concluded that HOXA9 gene might be involved in the pathogenesis of AML and played as a worse prognostic factor in AML. Keywords Gene  Acute myeloid leukemia  AML  Prognosis  Pathogenesis

Introduction HOXA9 gene is one of the highly conserved homeobox gene families which is localized on the human chromosome 7p15. HOXA9 is relevant not only to the function of the early hemopoietic stem cells, it also gets involved at the late differentiation and orientation stages of hemopoietic stem cells. The abnormal expression of HOXA9 was reported to affect the proliferation, differentiation, and apoptosis of hemopoietic cells [1], or even lead to leukemia [2, 3]. Another study [4] showed that HOXA9 gene expression was closely related to the incidence of leukemia in humans. In the present study, we sought to further investigate the HOXA9 gene expression in 54 patients with acute myeloid leukemia (AML) to determine the relationship between HOXA9 gene expression and AML pathogenesis and prognosis. Here, we show that HOXA9 mRNA was expressed in 22/54 (40.74 %) AML patients. Importantly, the complete remission rate in these patients was also significantly lower than that of HOXA9 non-expressors following the chemotherapy.

Materials and Methods Human Subjects

De-Peng Li and Zhen-Yu Li contributed equally to this study. D.-P. Li  Z.-Y. Li  W. Sang  H. Cheng  X.-Y. Pan  K.-L. Xu (&) Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, No.99 West Huaihai Road, Xuzhou 221002, China e-mail: [email protected]

In this study, the experimental group composed of 54 patients of acute myeloid leukemia that were admitted to our hospital during the period from October 2001 to March 2004. Among these 54 patients, 32 cases were admitted to the hospital for the first time, 13 cases presented with recurrent disease