Co-expression of ATP binding cassette transporters is associated with poor prognosis in acute myeloid leukemia

Abstract

Abstract. Chemotherapy failure remains a challenge when treating patients with acute myeloid leukemia (AML), who often suffer from persistent or relapsed disease. The multidrug resistance (MDR) mediated by efflux transporters of the ATP binding cassette (ABC) superfamily is a major obstacle for successful chemotherapy. The present study aimed to elucidate whether the expression of ABC transporters was associated with prognostic factors and responses to chemotherapy in patients with AML, with particular focus on whether co-expression of multiple ABC transporters resulted in a worse prognosis. In the present study, the mRNA expression levels of ABC transporters ABCB1, ABCB4, ABCC1, ABCC4 and ABCG2 in bone marrow (BM) mononuclear cell (MNC) samples from 96 de novo patients with AML and in the peripheral blood (PB) MNC samples from 22 normal individuals were investigated using reverse transcription-quantitative polymerase chain reaction analysis. It was revealed that ABCB1, ABCC1, ABCC4 and ABCG2 were expressed at higher levels in patients with AML compared with normal individuals, whereas ABCB4 had a lower expression level. The expression of ABCB4 in patients with AML was significantly lower than in normal individuals (P<0.001). Patients risk status was associated with ABCB1 (P= 0.037), ABCC1 (P= 0.047), ABCC4 (P=0.015) and ABCG2 (P=0.027). The 4 genes were expressed a significantly higher levels in the poor response group compared with the good response group (ABCB1, P= 0.014; ABCC1, P= 0.021; ABCC4, P= 0.005; ABCG2, P= 0.009). The overexpression of the 4 ABC transporters and the complete remission rate were inversely correlated (P<0.001). These results suggest that the co-expression of multiple ABC transporters may contribute to a worse prognosis in AML.

Generation and Characterization of anAbcc1Humanized Mouse Model (hABCC1flx/flx) with Knockout Capability

“…Nevertheless, ABCC1 also plays a role in the chemoresistance of different cancers. For instance, high ABCC1 expression is a negative prognostic factor in cases of soft tissue sarcoma (Citti et al, 2012;Martin-Broto et al, 2014) and acute myeloid and lymphoblastic leukemia (van der Kolk et al, 2000;Winter et al, 2013;Liu et al, 2018). Furthermore, this correlation has been shown for neuroblastoma patients.…”

WYE-354 restores Adriamycin sensitivity in multidrug-resistant acute myeloid leukemia cell lines

“…The role of ABCB1 in mediating MDR in cancer cells has been extensively documented in different types of cancer. The overexpression of ABCB1 is associated with poor clinical response to chemotherapy in patients with AML (28). Therefore, the development or identification of safe and effective ABCB1 inhibitors is of particular interest.…”

Expression Profile Screening and Bioinformatics Analysis of Circrna, Lncrna and Mrna in Acute Myeloid Leukemia Drug-Resistance Cells

“…However, multidrug resistance and treatment are key factors in the failure of leukemia treatment. Several factors are involved in the mechanism of leukemia resistance, including ABC transporter-mediated multidrug resistance [17], DNA repair abnormalities [18], variations in the bone marrow microenvironment [19], and abnormal expression of noncoding RNAs including circRNA, miRNA, and LncRNA [20]. Undeniably, ncRNAs have opened up new prospects for AML diagnosis, prognosis, and treatment.…”