The role of c-Myb and ABCG2/BCRP in the drug resistance of mature T-cell lymphomas

先前，我们已经表明AP-1家族成员FRA-2在成人T细胞白血病/淋巴瘤（ATLL）中始终以高水平表达，并上调CCR 4以及几种原癌基因（如c-Myb，MDM 2和BCL 6）的表达。在这里，我们确定了ABC转运蛋白，ABCG 2/BCRP，作为一个目标基因的c-Myb在成熟的T细胞淋巴瘤，包括ATLL和皮肤T细胞淋巴瘤（CTCL）。检测ATLL细胞中c-Myb和ABCG 2/BCRP的转录和蛋白表达。此外，Ko 143，一种选择性ABCG 2/BCRP抑制剂，增强阿霉素对ATLL细胞系的抗肿瘤活性。综上所述，我们的研究结果支持c-Myb-ABCG 2/BCRP通路在成熟T细胞淋巴瘤的化疗耐药性中起作用的观点。

Previously, we have shown that an AP-1 family member, FRA-2, is consistently expressed at high levels in Adult T-cell leukemia/lymphoma (ATLL) and up-regulates the expression of CCR4 as well as that of several proto-oncogenes such as c-Myb, MDM2, and BCL6. Here, we identified an ABC transporter, ABCG2/BCRP, as a target gene of c-Myb in mature T-cell lymphomas including ATLL and cutaneous T-cell lymphomas (CTCLs). We detected the transcripts and proteins of c-Myb and ABCG2/BCRP in ATLL cells. Furthermore, Ko143, a selective ABCG2/BCRP inhibitor, enhanced the antitumor activity of doxorubicin against ATLL cell lines. Taken together, our findings support the notion that the c-Myb-ABCG2/BCRP pathway plays a role in chemoresistance of mature T-cell lymphomas.