Evidence map›Paper›PMID 29631596›Full record

ArticleJournal of translational medicine2018

Association of genetic polymorphisms in genes involved in Ara-C and dNTP metabolism pathway with chemosensitivity and prognosis of adult acute myeloid leukemia (AML).

Ke-Wei Zhu, Peng Chen, Dao-Yu Zhang, Han Yan, Han Liu, Li-Na Cen, Yan-Ling Liu, Shan Cao, Gan Zhou, Hui Zeng and 3 more

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

23 citing papers in PubMed, 32 citations in OpenAlex.

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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

13 authors at 3 institutions in 1 country.

Ke-Wei ZhuDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410078, People's Republic of China.
Peng ChenDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410078, People's Republic of China.
Dao-Yu ZhangDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410078, People's Republic of China.
Han YanDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410078, People's Republic of China.
Han LiuDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410078, People's Republic of China.
Li-Na CenDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410078, People's Republic of China.
Yan-Ling LiuDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410078, People's Republic of China.
Shan CaoDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410078, People's Republic of China.
Gan ZhouDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410078, People's Republic of China.
Hui ZengDepartment of Hematology, Xiangya Hospital, Central South University, Changsha, 410078, People's Republic of China.
Shu-Ping ChenDepartment of Hematology, Xiangya Hospital, Central South University, Changsha, 410078, People's Republic of China.
Xie-Lan ZhaoDepartment of Hematology, Xiangya Hospital, Central South University, Changsha, 410078, People's Republic of China.
Xiao-Ping ChenDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410078, People's Republic of China. chenxp74@hotmail.com.
PharmacoGenetics (China) · CNCentral South University · CNXiangya Hospital Central South University · CN

Funding

Chinese National Science Foundation 81422052Chinese National Science Foundation 81673518the National key R&D program 2017YFC0909302
6 · The paper itself

Abstract

backgroundCytarabine arabinoside (Ara-C) has been the core of chemotherapy for adult acute myeloid leukemia (AML). Ara-C undergoes a three-step phosphorylation into the active metabolite Ara-C triphosphosphate (ara-CTP). Several enzymes are involved directly or indirectly in either the formation or detoxification of ara-CTP.

methodsA total of 12 eQTL (expression Quantitative Trait Loci) single nucleotide polymorphisms (SNPs) or tag SNPs in 7 genes including CMPK1, NME1, NME2, RRM1, RRM2, SAMHD1 and E2F1 were genotyped in 361 Chinese non-M3 AML patients by using the Sequenom Massarray system. Association of the SNPs with complete remission (CR) rate after Ara-C based induction therapy, relapse-free survival (RFS) and overall survival (OS) were analyzed.

resultsThree SNPs were observed to be associated increased risk of chemoresistance indicated by CR rate (NME2 rs3744660, E2F1 rs3213150, and RRM2 rs1130609), among which two (rs3744660 and rs1130609) were eQTL. Combined genotypes based on E2F1 rs3213150 and RRM2 rs1130609 polymorphisms further increased the risk of non-CR. The SAMHD1 eQTL polymorphism rs6102991 showed decreased risk of non-CR marginally (P = 0.055). Three SNPs (NME1 rs3760468 and rs2302254, and NME2 rs3744660) were associated with worse RFS, and the RRM2 rs1130609 polymorphism was marginally associated with worse RFS (P = 0.085) and OS (P = 0.080). Three SNPs (NME1 rs3760468, NME2 rs3744660, and RRM1 rs183484) were associated with worse OS in AML patients.

conclusionData from our study demonstrated that SNPs in Ara-C and dNTP metabolic pathway predict chemosensitivity and prognosis of AML patients in China.

Indexed as

Genetic Association StudiesGenetic Predisposition to DiseaseAdolescentAdultAgedCytarabineDisease-Free SurvivalFemaleGene Expression Regulation, LeukemicHumansLeukemia, Myeloid, AcuteLogistic ModelsMaleMiddle AgedMultivariate AnalysisNeoplasm ProteinsCytarabineNeoplasm ProteinsNucleotidesAdult acute myeloid leukaemia (AML)Cytarabine arabinoside (Ara-C)Single nucleotide polymorphisms (SNPs)

Identifiers

PMID29631596
PMCPMC5892020
OpenAlexW2802062021

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Registered trials

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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.