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; B. S. 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. Park; K. 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

doi:10.1093/annonc/mds532

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, B. S. 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

Department of Biomedical Sciences

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66 Citations (Scopus)

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 language	English
Pages (from-to)	756-760
Number of pages	5
Journal	Annals of Oncology
Volume	24
Issue number	3
DOIs	https://doi.org/10.1093/annonc/mds532
Publication status	Published - 2013 Mar

Keywords

Abcg
Chronic myeloid leukemia
Clinical response
Imatinib trough concentration

ASJC Scopus subject areas

Hematology
Oncology

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10.1093/annonc/mds532

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Seong, S. J., Lim, M., Sohn, S. K., Moon, J. H., Oh, S. J., Kim, B. S., 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., ... Yoon, Y. R. (2013). Influence of enzyme and transporter polymorphisms on trough imatinib concentration and clinical response in chronic myeloid leukemia patients. Annals of Oncology, 24(3), 756-760. https://doi.org/10.1093/annonc/mds532

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, pp. 756-760. https://doi.org/10.1093/annonc/mds532

@article{8562110a1eb34e998229efaae14da556,

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

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",

keywords = "Abcg, Chronic myeloid leukemia, Clinical response, Imatinib trough concentration",

author = "Seong, {S. J.} and M. Lim and Sohn, {S. K.} and Moon, {J. H.} and Oh, {S. J.} and Kim, {B. S.} and Ryoo, {H. M.} and Chung, {J. S.} and Joo, {Y. D.} and Bang, {S. M.} and Jung, {C. W.} and Kim, {D. H.} and Park, {S. Y.} and Yoon, {S. S.} and I. Kim and Lee, {H. G.} and Won, {J. H.} and Min, {Y. H.} and Cheong, {J. W.} and Park, {J. S.} and Eom, {K. S.} and Hyun, {M. S.} and Kim, {M. K.} and H. Kim and Park, {M. R.} and J. Park and Kim, {C. S.} and Kim, {H. J.} and Kim, {Y. K.} and Park, {E. K.} and Zang, {D. Y.} and Jo, {D. Y.} and Lee, {H. W.} and Yoon, {Y. R.}",

year = "2013",

month = mar,

doi = "10.1093/annonc/mds532",

language = "English",

volume = "24",

pages = "756--760",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Elsevier Ltd",

number = "3",

}

TY - JOUR

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, B. S.

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

Y1 - 2013/3

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

UR - http://www.scopus.com/inward/record.url?scp=84874568893&partnerID=8YFLogxK

U2 - 10.1093/annonc/mds532

DO - 10.1093/annonc/mds532

M3 - Article

C2 - 23117072

AN - SCOPUS:84874568893

SN - 0923-7534

VL - 24

SP - 756

EP - 760

JO - Annals of Oncology

JF - Annals of Oncology

IS - 3

ER -

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

Abstract

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