Homeobox gene HOXA7 and chemotherapy resistance in acute myeloid leukemia (AML)

Acute leukemia results from abnormal proliferation of either myeloid (acute myeloid leukemia [AML]) or lymphoid (acute lymphoid leukemia [ALL]) progenitor cells. Several members of the homeobox gene family have been implicated in the development of leukemia. Recent studies in the BXH-2 strain of mice, which spontaneously develop myeloid leukemias show that 15% of these leukemias express the homeobox gene Meis1, and often there is co-expression of two other homeobox genes, Hoxa9 and Hoxa7, thus suggesting that these genes cooperate in causing leukemia. Co-expression of MEIS1, HOXA9 and HOXA7 has been demonstrated in cultured and primary human myeloid leukemia cells. There is a suggestion that expression of HOXA9 is associated with poorer response to therapy. Additionally, in a recent study published by Afonja et al. 2000, HOXA7 expression tended to correlate with older age and poorer response to induction chemotherapy. To further characterize the role of HOXA7 in determining effective response to chemotherapy, we studied the effects of overexpression of HOXA7 on in-vitro drug response in K562 myeloid leukemia cells which are known to express MEIS1, HOXA9 but not HOXA7 (Afonja et al. 2000). The aim of this study was to determine if enforced expression HOXA7 gene would induce a chemoresistance phenotype. HOXA7 was stably transfected into K562 cells, which were then exposed to different chemotherapy drugs. Cell survival and viability were determined using cell proliferation assay. We observed that K562 cells stably transfected with HOXA7 were less responsive to 3 chemotherapeutic agent tested (PS341, Ara-C and Doxorubicin). We conclude that over expression HOXA7 may affect response to certain chemotherapeutic agents.