HOX proteins and leukemia

Abstract

HOX and three amino acid loop extension (TALE) proteins cooperate to induce transformation in mouse leukemia models, and are dysregulated in a variety of human leukemias. Despite decades of research, the mechanism of action for Hox proteins in embryogenesis and hematopoiesis remains unclear. Recent studies on the roles of Hoxa9 and Meis1 in leukemia has led to a wealth of new data, but their molecular mechanisms of action and synergy remain obscure. Advances in genome-wide technologies offer new avenues for understanding how homeodomain-containing transcription factors exert their programs in normal and neoplastic development.

Keywords: HOX; leukemia.

Figure 1

Organization of the clustered mammalian HOX genes. HOX genes form linear arrays on 4 different chromosomes and exhibit significant homology to the Drosophila HOM-C clustered homeotic genes.

Figure 2

HOXA9 and MEIS1 expression levels in AML patient samples. Expression data from 285 leukemias [104] was analyzed using the co-expression module at oncomine.org and shows the correlation between HOXA9 and MEIS1 expression [70]. MLL-fusion cases represent only 7% of cases in this study [104].

Figure 3

Possible modes of cooperation between Hoxa9 and Meis1. No single model is completely supported by current evidence; rather it is likely that targets of Hoxa9 and Meis1 are regulated by a combination of these mechanisms.