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Inherited genetic variants associated with glucocorticoid sensitivity in leukaemia cells

Identification of genetic variants associated with glucocorticoids (GC) sensitivity of leukaemia cells may provide insight into potential drug targets and tailored therapy. In the present study, within 72 leukaemic cell lines derived from Japanese patients with B‐cell precursor acute lymphoblastic l...

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Autores principales: Shinohara, Tamao, Urayama, Kevin Y., Watanabe, Atsushi, Akahane, Koshi, Goi, Kumiko, Huang, Meixian, Kagami, Keiko, Abe, Masako, Sugita, Kanji, Okada, Yukinori, Goto, Hiroaki, Minegishi, Masayoshi, Iwamoto, Shotaro, Inukai, Takeshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701530/
https://www.ncbi.nlm.nih.gov/pubmed/33002292
http://dx.doi.org/10.1111/jcmm.15882
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author Shinohara, Tamao
Urayama, Kevin Y.
Watanabe, Atsushi
Akahane, Koshi
Goi, Kumiko
Huang, Meixian
Kagami, Keiko
Abe, Masako
Sugita, Kanji
Okada, Yukinori
Goto, Hiroaki
Minegishi, Masayoshi
Iwamoto, Shotaro
Inukai, Takeshi
author_facet Shinohara, Tamao
Urayama, Kevin Y.
Watanabe, Atsushi
Akahane, Koshi
Goi, Kumiko
Huang, Meixian
Kagami, Keiko
Abe, Masako
Sugita, Kanji
Okada, Yukinori
Goto, Hiroaki
Minegishi, Masayoshi
Iwamoto, Shotaro
Inukai, Takeshi
author_sort Shinohara, Tamao
collection PubMed
description Identification of genetic variants associated with glucocorticoids (GC) sensitivity of leukaemia cells may provide insight into potential drug targets and tailored therapy. In the present study, within 72 leukaemic cell lines derived from Japanese patients with B‐cell precursor acute lymphoblastic leukaemia (ALL), we conducted genome‐wide genotyping of single nucleotide polymorphisms (SNP) and attempted to identify genetic variants associated with GC sensitivity and NR3C1 (GC receptor) gene expression. IC50 measures for prednisolone (Pred) and dexamethasone (Dex) were available using an alamarBlue cell viability assay. IC50 values of Pred showed the strongest association with rs904419 (P = 4.34 × 10(−8)), located between the FRMD4B and MITF genes. The median IC50 values of prednisolone for cell lines with rs904419 AA (n = 13), AG (n = 31) and GG (n = 28) genotypes were 0.089, 0.139 and 297 µmol/L, respectively. For dexamethasone sensitivity, suggestive association was observed for SNP rs2306888 (P = 1.43 × 10(−6)), a synonymous SNP of the TGFBR3 gene. For NR3C1 gene expression, suggestive association was observed for SNP rs11982167 (P = 6.44 × 10(−8)), located in the PLEKHA8 gene. These genetic variants may affect GC sensitivity of ALL cells and may give rise to opportunities in personalized medicine for effective and safe chemotherapy in ALL patients.
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spelling pubmed-77015302020-12-08 Inherited genetic variants associated with glucocorticoid sensitivity in leukaemia cells Shinohara, Tamao Urayama, Kevin Y. Watanabe, Atsushi Akahane, Koshi Goi, Kumiko Huang, Meixian Kagami, Keiko Abe, Masako Sugita, Kanji Okada, Yukinori Goto, Hiroaki Minegishi, Masayoshi Iwamoto, Shotaro Inukai, Takeshi J Cell Mol Med Original Articles Identification of genetic variants associated with glucocorticoids (GC) sensitivity of leukaemia cells may provide insight into potential drug targets and tailored therapy. In the present study, within 72 leukaemic cell lines derived from Japanese patients with B‐cell precursor acute lymphoblastic leukaemia (ALL), we conducted genome‐wide genotyping of single nucleotide polymorphisms (SNP) and attempted to identify genetic variants associated with GC sensitivity and NR3C1 (GC receptor) gene expression. IC50 measures for prednisolone (Pred) and dexamethasone (Dex) were available using an alamarBlue cell viability assay. IC50 values of Pred showed the strongest association with rs904419 (P = 4.34 × 10(−8)), located between the FRMD4B and MITF genes. The median IC50 values of prednisolone for cell lines with rs904419 AA (n = 13), AG (n = 31) and GG (n = 28) genotypes were 0.089, 0.139 and 297 µmol/L, respectively. For dexamethasone sensitivity, suggestive association was observed for SNP rs2306888 (P = 1.43 × 10(−6)), a synonymous SNP of the TGFBR3 gene. For NR3C1 gene expression, suggestive association was observed for SNP rs11982167 (P = 6.44 × 10(−8)), located in the PLEKHA8 gene. These genetic variants may affect GC sensitivity of ALL cells and may give rise to opportunities in personalized medicine for effective and safe chemotherapy in ALL patients. John Wiley and Sons Inc. 2020-10-01 2020-11 /pmc/articles/PMC7701530/ /pubmed/33002292 http://dx.doi.org/10.1111/jcmm.15882 Text en © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Shinohara, Tamao
Urayama, Kevin Y.
Watanabe, Atsushi
Akahane, Koshi
Goi, Kumiko
Huang, Meixian
Kagami, Keiko
Abe, Masako
Sugita, Kanji
Okada, Yukinori
Goto, Hiroaki
Minegishi, Masayoshi
Iwamoto, Shotaro
Inukai, Takeshi
Inherited genetic variants associated with glucocorticoid sensitivity in leukaemia cells
title Inherited genetic variants associated with glucocorticoid sensitivity in leukaemia cells
title_full Inherited genetic variants associated with glucocorticoid sensitivity in leukaemia cells
title_fullStr Inherited genetic variants associated with glucocorticoid sensitivity in leukaemia cells
title_full_unstemmed Inherited genetic variants associated with glucocorticoid sensitivity in leukaemia cells
title_short Inherited genetic variants associated with glucocorticoid sensitivity in leukaemia cells
title_sort inherited genetic variants associated with glucocorticoid sensitivity in leukaemia cells
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701530/
https://www.ncbi.nlm.nih.gov/pubmed/33002292
http://dx.doi.org/10.1111/jcmm.15882
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