The Role of the HOXA Gene Family in Acute Myeloid Leukemia

Abstract

The <i>HOXA</i> gene family is associated with various cancer types. However, the role of <i>HOXA</i> genes in acute myeloid leukemia (AML) have not been comprehensively studied. We compared the transcriptional expression, survival data, and network analysis of <i>HOXA</i>-associated signaling pathways in patients with AML using the ONCOMINE, GEPIA, LinkedOmics, cBioPortal, and Metascape databases. We observed that <i>HOXA2-10</i> mRNA expression levels were significantly upregulated in AML and that high <i>HOXA1-10</i> expression was associated with poor AML patient prognosis. The <i>HOXA</i> 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 <i>HOXA</i> gene upregulation: GO:0048706: embryonic skeletal system development; R-HSA-5617472: activation of <i>HOX</i> genes in anterior hindbrain development during early embryogenesis; GO:0060216: definitive hemopoiesis; hsa05202: transcriptional mis-regulation in cancer; and GO:0045638: negative regulation of myeloid cell differentiation, and they were significantly regulated due to alterations affecting the <i>HOXA</i> genes. This study identified <i>HOXA3-10</i> genes as potential AML therapeutic targets and prognostic markers.