Evidence map›Paper›PMID 32221476›Full record

ArticlePediatric research2021

Childhood acute lymphoblastic leukemia mercaptopurine intolerance is associated with NUDT15 variants.

Der-Shiun Wang, Chih-Hsiang Yu, Chien-Yu Lin, Ya-Hsuan Chang, Kai-Hsin Lin, Dong-Tsamn Lin, Shiann-Tarng Jou, Meng-Yao Lu, Hsiu-Hao Chang, Shu-Wha Lin and 2 more

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Article in Pediatric research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.0field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. PACSIN proteins in vivo: Roles in development and physiology.Acta physiologica (Oxford, England) · 2022
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Der-Shiun Wang *Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chih-Hsiang Yu *Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan.
Chien-Yu LinInstitute of Statistical Science, Academia Sinica, Taipei, Taiwan.
Ya-Hsuan ChangInstitute of Statistical Science, Academia Sinica, Taipei, Taiwan.
Kai-Hsin LinDepartment of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
Dong-Tsamn LinDepartment of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
Shiann-Tarng JouDepartment of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
Meng-Yao LuDepartment of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
Hsiu-Hao ChangDepartment of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
Shu-Wha LinDepartment of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan.
Hsuan-Yu ChenInstitute of Statistical Science, Academia Sinica, Taipei, Taiwan.
Yung-Li YangDepartment of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan. yangyl92@ntu.edu.tw.
National Taiwan University · TWInstitute of Statistical Science, Academia Sinica · TWNational Taiwan University Hospital · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMercaptopurine-induced neutropenia can interrupt chemotherapy and expose patients to infection during childhood acute lymphoblastic leukemia (ALL) treatment. Previously, six candidate gene variants associated with mercaptopurine intolerance were reported. Herein, we investigated the association between the mean tolerable dose of mercaptopurine and these genetic variants in Taiwanese patients.

methodsIn total, 294 children with ALL were treated at the National Taiwan University Hospital from April 1997 to December 2017. Germline variants were analyzed for NUDT15, SUCLA2, TPMT, ITPA, PACSIN2, and MRP4. Mean daily tolerable doses of mercaptopurine in the continuation phase of treatment were correlated with these genetic variants.

resultsMercaptopurine intolerance was significantly associated with polymorphisms in NUDT15 (P value < 0.0001). Patients with SUCLA2 variants received lower mercaptopurine doses (P value = 0.0119). The mean mercaptopurine doses did not differ among patients with TPMT, ITPA, MRP4, and PACSIN2 polymorphisms (P value = 0.9461, 0.5818, and 0.7951, respectively). After multivariable linear regression analysis, only NUDT15 variants retained their clinically significant correlation with mercaptopurine intolerance (P value < 0.0001).

conclusionIn this cohort, the major genetic determinant of mercaptopurine intolerance was NUDT15 in Taiwanese patients. IMPACT: NUDT15 causes mercaptopurine intolerance in children with ALL. The NUDT15 variant is a stronger predictor of mercaptopurine intolerance than TPMT in a Taiwanese cohort. This finding is similar with studies performed on Asian populations rather than Caucasians. Pre-emptive genotyping of the patients' NUDT15 before administering mercaptopurine may be more helpful than genotyping TPMT in Asians.

Indexed as

Pharmacogenomic VariantsPolymorphism, Single NucleotideAntimetabolites, AntineoplasticHumansMercaptopurineMethyltransferasesNeutropeniaNudix HydrolasesPrecursor Cell Lymphoblastic Leukemia-LymphomaPyrophosphatasesRetrospective StudiesRisk AssessmentRisk FactorsTaiwanAntimetabolites, AntineoplasticMercaptopurineMethyltransferasesNudix HydrolasesNUDT15 protein, humanPyrophosphatasesTPMT protein, human

Identifiers

PMID32221476
OpenAlexW3013495438

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.