Influence of enzyme and transporter polymorphisms on trough imatinib concentration and clinical response in chronic myeloid leukemia patients

S. J. Seong, M. Lim, S. K. Sohn, J. H. Moon, S. J. Oh, Byung Soo Kim, H. M. Ryoo, J. S. Chung, Y. D. Joo, S. M. Bang, C. W. Jung, D. H. Kim, S. Y. Park, S. S. Yoon, I. Kim, H. G. Lee, J. H. Won, Y. H. Min, J. W. Cheong, J. S. ParkK. S. Eom, M. S. Hyun, M. K. Kim, H. Kim, M. R. Park, J. Park, C. S. Kim, H. J. Kim, Y. K. Kim, E. K. Park, D. Y. Zang, D. Y. Jo, H. W. Lee, Y. R. Yoon

Research output: Contribution to journalArticle

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Abstract

Background: This study explored the impact of genetic polymorphisms in cytochrome P450 (CYP) enzymes and transporters on the plasma trough concentration of imatinib mesylate (IM) and clinical response in chronic myeloid leukemia (CML). Patients and methods: In total, 82 patients with CML who had been administered 400 mg IM daily for over 6 months were genotyped for 11 single-nucleotide polymorphisms in nine genes (CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC22A1, SLC22A2 and ABCG2) using blood samples. The trough imatinib concentration and clinical responses were assessed 6 months after the initiation of IM therapy. Results: The CC, CA and AA genotypes in ABCG2 421C>A gave significantly different frequencies for the major molecular response (MMR) (P = 0.02). However, no significant differences were fo nd between the genotypes of the CYP enzymes and transporters identified in this study and the imatinib plasma trough concentrations and clinical response frequencies, except for the correlation of ABCG2 with MMR. Conclusions: The results of the present study may indicate that the ABCG 421C>A genetic polymorphism influences the MMR of imatinib in patients with CML

Original languageEnglish
Article numbermds532
Pages (from-to)756-760
Number of pages5
JournalAnnals of Oncology
Volume24
Issue number3
DOIs
Publication statusPublished - 2013 Mar 1

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cytochrome P-450 Enzyme System
Enzymes
Cytochrome P-450 CYP3A
Genetic Polymorphisms
Genotype
Cytochrome P-450 CYP2D6
Single Nucleotide Polymorphism
Imatinib Mesylate
Genes

Keywords

  • Abcg
  • Chronic myeloid leukemia
  • Clinical response
  • Imatinib trough concentration

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Influence of enzyme and transporter polymorphisms on trough imatinib concentration and clinical response in chronic myeloid leukemia patients. / Seong, S. J.; Lim, M.; Sohn, S. K.; Moon, J. H.; Oh, S. J.; Kim, Byung Soo; Ryoo, H. M.; Chung, J. S.; Joo, Y. D.; Bang, S. M.; Jung, C. W.; Kim, D. H.; Park, S. Y.; Yoon, S. S.; Kim, I.; Lee, H. G.; Won, J. H.; Min, Y. H.; Cheong, J. W.; Park, J. S.; Eom, K. S.; Hyun, M. S.; Kim, M. K.; Kim, H.; Park, M. R.; Park, J.; Kim, C. S.; Kim, H. J.; Kim, Y. K.; Park, E. K.; Zang, D. Y.; Jo, D. Y.; Lee, H. W.; Yoon, Y. R.

In: Annals of Oncology, Vol. 24, No. 3, mds532, 01.03.2013, p. 756-760.

Research output: Contribution to journalArticle

Seong, SJ, Lim, M, Sohn, SK, Moon, JH, Oh, SJ, Kim, BS, Ryoo, HM, Chung, JS, Joo, YD, Bang, SM, Jung, CW, Kim, DH, Park, SY, Yoon, SS, Kim, I, Lee, HG, Won, JH, Min, YH, Cheong, JW, Park, JS, Eom, KS, Hyun, MS, Kim, MK, Kim, H, Park, MR, Park, J, Kim, CS, Kim, HJ, Kim, YK, Park, EK, Zang, DY, Jo, DY, Lee, HW & Yoon, YR 2013, 'Influence of enzyme and transporter polymorphisms on trough imatinib concentration and clinical response in chronic myeloid leukemia patients', Annals of Oncology, vol. 24, no. 3, mds532, pp. 756-760. https://doi.org/10.1093/annonc/mds532
Seong, S. J. ; Lim, M. ; Sohn, S. K. ; Moon, J. H. ; Oh, S. J. ; Kim, Byung Soo ; Ryoo, H. M. ; Chung, J. S. ; Joo, Y. D. ; Bang, S. M. ; Jung, C. W. ; Kim, D. H. ; Park, S. Y. ; Yoon, S. S. ; Kim, I. ; Lee, H. G. ; Won, J. H. ; Min, Y. H. ; Cheong, J. W. ; Park, J. S. ; Eom, K. S. ; Hyun, M. S. ; Kim, M. K. ; Kim, H. ; Park, M. R. ; Park, J. ; Kim, C. S. ; Kim, H. J. ; Kim, Y. K. ; Park, E. K. ; Zang, D. Y. ; Jo, D. Y. ; Lee, H. W. ; Yoon, Y. R. / Influence of enzyme and transporter polymorphisms on trough imatinib concentration and clinical response in chronic myeloid leukemia patients. In: Annals of Oncology. 2013 ; Vol. 24, No. 3. pp. 756-760.
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abstract = "Background: This study explored the impact of genetic polymorphisms in cytochrome P450 (CYP) enzymes and transporters on the plasma trough concentration of imatinib mesylate (IM) and clinical response in chronic myeloid leukemia (CML). Patients and methods: In total, 82 patients with CML who had been administered 400 mg IM daily for over 6 months were genotyped for 11 single-nucleotide polymorphisms in nine genes (CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC22A1, SLC22A2 and ABCG2) using blood samples. The trough imatinib concentration and clinical responses were assessed 6 months after the initiation of IM therapy. Results: The CC, CA and AA genotypes in ABCG2 421C>A gave significantly different frequencies for the major molecular response (MMR) (P = 0.02). However, no significant differences were fo nd between the genotypes of the CYP enzymes and transporters identified in this study and the imatinib plasma trough concentrations and clinical response frequencies, except for the correlation of ABCG2 with MMR. Conclusions: The results of the present study may indicate that the ABCG 421C>A genetic polymorphism influences the MMR of imatinib in patients with CML",
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T1 - Influence of enzyme and transporter polymorphisms on trough imatinib concentration and clinical response in chronic myeloid leukemia patients

AU - Seong, S. J.

AU - Lim, M.

AU - Sohn, S. K.

AU - Moon, J. H.

AU - Oh, S. J.

AU - Kim, Byung Soo

AU - Ryoo, H. M.

AU - Chung, J. S.

AU - Joo, Y. D.

AU - Bang, S. M.

AU - Jung, C. W.

AU - Kim, D. H.

AU - Park, S. Y.

AU - Yoon, S. S.

AU - Kim, I.

AU - Lee, H. G.

AU - Won, J. H.

AU - Min, Y. H.

AU - Cheong, J. W.

AU - Park, J. S.

AU - Eom, K. S.

AU - Hyun, M. S.

AU - Kim, M. K.

AU - Kim, H.

AU - Park, M. R.

AU - Park, J.

AU - Kim, C. S.

AU - Kim, H. J.

AU - Kim, Y. K.

AU - Park, E. K.

AU - Zang, D. Y.

AU - Jo, D. Y.

AU - Lee, H. W.

AU - Yoon, Y. R.

PY - 2013/3/1

Y1 - 2013/3/1

N2 - Background: This study explored the impact of genetic polymorphisms in cytochrome P450 (CYP) enzymes and transporters on the plasma trough concentration of imatinib mesylate (IM) and clinical response in chronic myeloid leukemia (CML). Patients and methods: In total, 82 patients with CML who had been administered 400 mg IM daily for over 6 months were genotyped for 11 single-nucleotide polymorphisms in nine genes (CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC22A1, SLC22A2 and ABCG2) using blood samples. The trough imatinib concentration and clinical responses were assessed 6 months after the initiation of IM therapy. Results: The CC, CA and AA genotypes in ABCG2 421C>A gave significantly different frequencies for the major molecular response (MMR) (P = 0.02). However, no significant differences were fo nd between the genotypes of the CYP enzymes and transporters identified in this study and the imatinib plasma trough concentrations and clinical response frequencies, except for the correlation of ABCG2 with MMR. Conclusions: The results of the present study may indicate that the ABCG 421C>A genetic polymorphism influences the MMR of imatinib in patients with CML

AB - Background: This study explored the impact of genetic polymorphisms in cytochrome P450 (CYP) enzymes and transporters on the plasma trough concentration of imatinib mesylate (IM) and clinical response in chronic myeloid leukemia (CML). Patients and methods: In total, 82 patients with CML who had been administered 400 mg IM daily for over 6 months were genotyped for 11 single-nucleotide polymorphisms in nine genes (CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC22A1, SLC22A2 and ABCG2) using blood samples. The trough imatinib concentration and clinical responses were assessed 6 months after the initiation of IM therapy. Results: The CC, CA and AA genotypes in ABCG2 421C>A gave significantly different frequencies for the major molecular response (MMR) (P = 0.02). However, no significant differences were fo nd between the genotypes of the CYP enzymes and transporters identified in this study and the imatinib plasma trough concentrations and clinical response frequencies, except for the correlation of ABCG2 with MMR. Conclusions: The results of the present study may indicate that the ABCG 421C>A genetic polymorphism influences the MMR of imatinib in patients with CML

KW - Abcg

KW - Chronic myeloid leukemia

KW - Clinical response

KW - Imatinib trough concentration

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