HOX GENE EXPRESSION IN HUMAN B-CELL PROGENITOR LEUKEMIA CELL LINES EXPRESSING E2A-PBX1 ONCOGENE

Abstract

Introduction. Acute lymphoblastic leukemia (ALL) is diagnosed mainly in children (2/3 of diseases) making this type of leukemia one of the most common oncological diseases among children. Oncogenes are involved in the development of ALL, in particular the product of chromosomes 1 and 19 translocation, the oncogene E2A-PBX1 that codes for E2A-PBX1 chimeric oncoprotein with strong transcription activation properties as well as oncogenes of HOX family, mainly HOXA and HOXB cluster genes. E2A-PBX1 chimeric oncoprotein and НОХА proteins are associated in vivo with factors participating in epigenetic regulation of gene expression such as chromatin modifying and remodeling enzymes that partially determines their oncogenic properties. In previous studies we obtained data indicating genetic interactions of E2A-PBX1 and НОХ genes participating in leukemia development.The aim of this research was to confirm the role of Е2А – РВХ1 oncogene in the activation of the expression of НОХА cluster genes coding for the proteins with high oncogenic potential.Materials and methods. The objects of the study were four B cell progenitor (pre-B) leukemia cell lines: RCH-ACV, KASUMI-2, 697 and NALM-6. Standard polymerase chain reaction (PCR) was used for the identification of chromosome 1 and 19 translocation product, E2A-PBX1 oncogene and its expression. Method of reverse transcription coupled with quantitative polymerase chain reaction (Q-RT-PCR) was used for the analysis of 11 HOXA cluster genes expression.Results. It is demonstrated that E2A-PBX1 oncogene is present and expressed in three studied human pre-B leukemia cell lines, RCH-ACV, KASUMI-2 and 697, while its expression is absent in NALM-6 cell line. High expression of 7 from 11 HOXА cluster genes is revealed in RCH-ACV, KASUMI-2 and 697 cell lines expressing E2A-PBX1 oncogene, whereas NALM-6 cell line, that does not express E2A-PBX1 oncogene, also does not express HOXA genes except low expression of two genes from this cluster.Conclusions. The data obtained in this study demonstrate that RCH-ACV, KASUMI-2 and 697 human leukemia pre-B cell lines, containing and expressing Е2А-РВХ1 oncogene, also express most of HOXA genes (7 genes of 11 genes) at high level in contrast to control NALM-6 cell line that does not comprise Е2А-РВХ1 oncogene and almost does not express НОХА genes. Therefore, the results of this study suggest the participation of strong transcriptional activator, chimeric oncoprotein Е2А-РВХ1, associated with chromatin modifying and remodeling enzymes, in the expression activation of HOXA cluster genes that also possess high oncogenic potential.