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Homozygote CRIM1 variant is associated with thiopurine-induced neutropenia in leukemic patients with both wildtype NUDT15 and TPMT.

ABSTRACT: BACKGROUND:NUDT15 and TPMT variants are strong genetic determinants of thiopurine-induced hematological toxicity that results in therapeutic failure in pediatric acute lymphoblastic leukemia (ALL). However, many patients with both wild-type (WT) NUDT15 and TPMT still suffer from thiopurine toxicity and therapeutic failure. METHODS:Whole-exome sequencing was done for discovery (N?=?244) and replication (N?=?76) cohorts. Age- and sex-adjusted multiple regression analyses of both WT patients were performed to identify (p?

SUBMITTER: Park Y

PROVIDER: S-EPMC7328279 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Homozygote CRIM1 variant is associated with thiopurine-induced neutropenia in leukemic patients with both wildtype NUDT15 and TPMT.

Park Yoomi Y Kim Hyery H Seo Heewon H Choi Jung Yoon JY Ma Youngeun Y Yun Sunmin S Min Byung-Joo BJ Seo Myung-Eui ME Yoo Keon Hee KH Kang Hyoung Jin HJ Im Ho Joon HJ Kim Ju Han JH

Journal of translational medicine 20200701 1

<h4>Background</h4>NUDT15 and TPMT variants are strong genetic determinants of thiopurine-induced hematological toxicity that results in therapeutic failure in pediatric acute lymphoblastic leukemia (ALL). However, many patients with both wild-type (WT) NUDT15 and TPMT still suffer from thiopurine toxicity and therapeutic failure.<h4>Methods</h4>Whole-exome sequencing was done for discovery (N = 244) and replication (N = 76) cohorts. Age- and sex-adjusted multiple regression analyses of both WT ...[more]

PMID: 32611418

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