Association between the concentration of imatinib in bone marrow mononuclear cells, mutation status of ABCB1 and therapeutic response in patients with chronic myelogenous leukemia

  • Authors:
    • Chang‑Xin Yin
    • Wei‑Wei Chen
    • Qing‑Xiu Zhong
    • Xue‑Jie Jiang
    • Zhi‑Xiang Wang
    • Xiao‑Dong Li
    • Jie‑Yu Ye
    • Rui Cao
    • Li‑Bing Liao
    • Fu‑Qun Wu
    • Dan Xu
    • Jian‑Sheng Zhong
    • Fan‑Yi Meng
  • View Affiliations

  • Published online on: March 2, 2016     https://doi.org/10.3892/etm.2016.3127
  • Pages: 2061-2065
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Low concentrations of imatinib (IM) in bone marrow cells have been linked with poor prognosis in patients with chronic myeloid leukemia (CML), which may be caused by the emergence of ATP‑binding cassette transporter B1 (ABCB1) mutations. The aim of present study was to investigate how clinical outcomes vary among patients with different single nucleotide polymorphisms (SNPs) of ABCB1. A total of 48 adult patients with CML and higher than median ABCB1 mRNA levels were selected for testing of ABCB1 SNPs. In 28 of the 48 patients, the IM concentration and expression levels of human organic cation transporter 1 (hOCT1) and ABCB1 in bone marrow mononuclear cells (BMMCs) were also tested. Correlations between treatment outcomes and IM concentration or the SNP status of ABCB1 were analyzed. Patients were classified by therapeutic response as major molecular response (MMR) (n=11), complete cytogenetic response (CCyR) (n=19) and non‑CCyR (n=18) groups. It was found that the concentration of IM in BMMCs of the CCyR group was significant higher than that of the resistant groups (P=0.013). In addition, the IM concentration was positively correlated with the expression of hOCT1 mRNA (R=0.456, P=0.033), but negatively correlated with the expression of ABCB1 mRNA (R=‑0.491, P=0.015). Furthermore, the mRNA expression level of ABCB1 was not associated with therapeutic response, but SNPs of the ABCB1 gene were associated with the response to IM. In conclusion, the concentration of IM in BMMCs may be regulated by the ABCB1 gene, and SNPs of the ABCB1 gene predict the therapeutic response to IM in patients with CML.
View References

Related Articles

Journal Cover

May-2016
Volume 11 Issue 5

Print ISSN: 1792-0981
Online ISSN:1792-1015

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Yin CX, Chen WW, Zhong QX, Jiang XJ, Wang ZX, Li XD, Ye JY, Cao R, Liao LB, Wu FQ, Wu FQ, et al: Association between the concentration of imatinib in bone marrow mononuclear cells, mutation status of ABCB1 and therapeutic response in patients with chronic myelogenous leukemia. Exp Ther Med 11: 2061-2065, 2016.
APA
Yin, C., Chen, W., Zhong, Q., Jiang, X., Wang, Z., Li, X. ... Meng, F. (2016). Association between the concentration of imatinib in bone marrow mononuclear cells, mutation status of ABCB1 and therapeutic response in patients with chronic myelogenous leukemia. Experimental and Therapeutic Medicine, 11, 2061-2065. https://doi.org/10.3892/etm.2016.3127
MLA
Yin, C., Chen, W., Zhong, Q., Jiang, X., Wang, Z., Li, X., Ye, J., Cao, R., Liao, L., Wu, F., Xu, D., Zhong, J., Meng, F."Association between the concentration of imatinib in bone marrow mononuclear cells, mutation status of ABCB1 and therapeutic response in patients with chronic myelogenous leukemia". Experimental and Therapeutic Medicine 11.5 (2016): 2061-2065.
Chicago
Yin, C., Chen, W., Zhong, Q., Jiang, X., Wang, Z., Li, X., Ye, J., Cao, R., Liao, L., Wu, F., Xu, D., Zhong, J., Meng, F."Association between the concentration of imatinib in bone marrow mononuclear cells, mutation status of ABCB1 and therapeutic response in patients with chronic myelogenous leukemia". Experimental and Therapeutic Medicine 11, no. 5 (2016): 2061-2065. https://doi.org/10.3892/etm.2016.3127