The Role of the HOXA Gene Family in Acute Myeloid Leukemia.

ABSTRACT

The HOXA gene family is associated with various cancer types. However, the role of HOXA genes in acute myeloid leukemia (AML) have not been comprehensively studied. We compared the transcriptional expression, survival data, and network analysis of HOXA-associated signaling pathways in patients with AML using the ONCOMINE, GEPIA, LinkedOmics, cBioPortal, and Metascape databases. We observed that HOXA2-10 mRNA expression levels were significantly upregulated in AML and that high HOXA1-10 expression was associated with poor AML patient prognosis. The HOXA genes were altered in ~18% of the AML samples, either in terms of amplification, deep deletion, or elevated mRNA expression. The following pathways were modulated by HOXA gene upregulation GO0048706 embryonic skeletal system development; R-HSA-5617472 activation of HOX genes in anterior hindbrain development during early embryogenesis; GO0060216 definitive hemopoiesis; hsa05202 transcriptional mis-regulation in cancer; and GO0045638 negative regulation of myeloid cell differentiation, and they were significantly regulated due to alterations affecting the HOXA genes. This study identified HOXA3-10 genes as potential AML therapeutic targets and prognostic markers.