Evidence map›Paper›PMID 33958640›Full record

ArticleScientific reports2021

Interplay between IL6 and CRIM1 in thiopurine intolerance due to hematological toxicity in leukemic patients with wild-type NUDT15 and TPMT.

Hyery Kim, Seungwon You, Yoomi Park, Jung Yoon Choi, Youngeun Ma, Kyung Tak Hong, Kyung-Nam Koh, Sunmin Yun, Kye Hwa Lee, Hee Young Shin and 5 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.6field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Article
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

15 authors at 5 institutions in 1 country.

Hyery Kim *Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
Seungwon You *Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.
Yoomi ParkSeoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.
Jung Yoon ChoiDepartment of Pediatrics, Seoul National University College of Medicine, Seoul, 03080, Korea.
Youngeun MaDepartment of Pediatrics, Seoul National University Bundang Hospital, Seoul, Korea.
Kyung Tak HongDepartment of Pediatrics, Seoul National University College of Medicine, Seoul, 03080, Korea.
Kyung-Nam KohDepartment of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
Sunmin YunSeoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.
Kye Hwa LeeSeoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.
Hee Young ShinDepartment of Pediatrics, Seoul National University College of Medicine, Seoul, 03080, Korea.
Suehyun LeeSeoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.
Keon Hee YooDepartment of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Ho Joon ImDepartment of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea. juhan@snu.ac.kr.
Hyoung Jin KangDepartment of Pediatrics, Seoul National University College of Medicine, Seoul, 03080, Korea. kanghj@snu.ac.kr.
Ju Han KimSeoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea. juhan@snu.ac.kr.
Seoul National University · KRUlsan College · KRAsan Medical Center · KRSamsung Medical Center · KRSeoul National University Bundang Hospital · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

NUDT15 and TPMT variants are strong genetic determinants of thiopurine-induced hematological toxicity. Despite the impact of homozygous CRIM1 on thiopurine toxicity, several patients with wild-type NUDT15, TPMT, and CRIM1 experience thiopurine toxicity, therapeutic failure, and relapse of acute lymphoblastic leukemia (ALL). Novel pharmacogenetic interactions associated with thiopurine intolerance from hematological toxicities were investigated using whole-exome sequencing for last-cycle 6-mercaptopurine dose intensity percentages (DIP) tolerated by pediatric ALL patients (N = 320). IL6 rs13306435 carriers (N = 19) exhibited significantly lower DIP (48.0 ± 27.3%) than non-carriers (N = 209, 69.9 ± 29.0%; p = 0.0016 and 0.0028 by t test and multiple linear regression, respectively). Among 19 carriers, 7 with both heterozygous IL6 rs13306435 and CRIM1 rs3821169 showed significantly decreased DIP (24.7 ± 8.9%) than those with IL6 (N = 12, 61.6 ± 25.1%) or CRIM1 (N = 94, 68.1 ± 28.4%) variants. IL6 and CRIM1 variants showed marked inter-ethnic variability. Four-gene-interplay models revealed the best odds ratio (8.06) and potential population impact [relative risk (5.73), population attributable fraction (58%), number needed to treat (3.67), and number needed to genotype (12.50)]. Interplay between IL6 rs13306435 and CRIM1 rs3821169 was suggested as an independent and/or additive genetic determinant of thiopurine intolerance beyond NUDT15 and TPMT in pediatric ALL.

Indexed as

AdolescentBone MarrowBone Morphogenetic Protein ReceptorsChildChild, PreschoolEthnicityExome SequencingFemaleHumansInfantInterleukin-6MaleMercaptopurineMethyltransferasesNudix HydrolasesPharmacogeneticsBone Morphogenetic Protein ReceptorsCRIM1 protein, humanIL6 protein, humanInterleukin-6MercaptopurineMethyltransferasesNudix HydrolasesNUDT15 protein, humanPyrophosphatasesTPMT protein, human

Identifiers

PMID33958640
PMCPMC8102572
OpenAlexW3157999615

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.