Expression of ABCC6 gene in Acute Myeloid Leukemia

Multidrug resistance (MDR) is a major impediment to the successful treatment of acute myeloid leukemia (AML). One of the known MDR mechanisms is the over expression of efflux pumps belonging to the superfamily of ABC transporters, such as P-glycoprotein (ABCB1), BCRP (ABCG2) and MRP1 (ABCC1) [1]. At present, little is known about the clinical relevance of other ABC-transporters in AML. However it was observed that patients with acute lymphoblastic leukemia presenting high MRPs expression, including MRP6, have unfavorable prognosis [2]. In this study, we investigated the expression of ABCB1, ABCC1, ABCG2 and ABCC6 genes in six healthy controls and in thirteen patients with AML, at diagnosis, after chemotherapy, at refractory disease and at relapse. Real-time PCR results showed that at diagnosis, compared to healthy subjects, all patients, except one, presented at least one among ABCB1/ABCC1/ABCC6 genes up-regulated; instead ABCG2 was always down-regulated. Moreover, we interestingly observed that three patients with poor prognosis exhibited higher level of ABCC6 mRNA after treatment compared to diagnosis and that in these patients also BCRP was up-regulated, sign of chemoresistance. We also observed that ninety percent of treated patients presented ABCG2 expression significantly higher after treatment than at diagnosis; thirty percent presented over expression of ABCB1 and only two patients showed ABCC1 up-regulation. In conclusion, our results showed a possible involvement of MRP6 in the development of MDR in AML and that BCRP has, more than MDR1 and MRP1, a relevant role in this mechanism. ABCC6 resulted up-regulated in thirty percent of treated AML patients, but further studies on a larger number of patients are necessary to establish if MRP6 may be involved in the treatment failure of AML and if co-expression of these ABC-transporters may have prognostic significance. REFERENCES 1. Brian C. Shaffer et al. Drug Resist Updat. 2012; 15(1-2): 62–69. 2. Plasschaert SL et al. Clin Cancer Res. 2005; 15;11(24 Pt 1):8661-8.