BACKGROUND: The genetic variants of the ARID5B gene have recently been reported to be associated with disease susceptibility and treatment outcome in childhood acute lymphoblastic leukemia (ALL). However, few studies have explored the association of ARID5B with sensitivities to chemotherapeutic agents. METHODS: We genotyped susceptibility-linked rs7923074 and rs10821936 as well as relapse-linked rs4948488, rs2893881, and rs6479778 of ARDI5B by direct sequencing of polymerase chain reaction (PCR) products in 72 B-cell precursor-ALL (BCP-ALL) cell lines established from Japanese patients. We also quantified their ARID5B expression levels by real-time reverse transcription PCR, and determined their 50% inhibitory concentration (IC50) values by alamarBlue assays in nine representative chemotherapeutic agents used for ALL treatment. RESULTS: No significant associations were observed in genotypes of the susceptibility-linked single nucleotide polymorphisms (SNPs) and the relapsed-linked SNPs with ARID5B gene expression levels. Of note, IC50 values of vincristine (VCR) (median IC50: 39.6 ng/ml) in 12 cell lines with homozygous genotype of risk allele (C) in the relapse-linked rs4948488 were significantly higher (p = 0.031 in Mann-Whitney U test) than those (1.04 ng/ml) in 60 cell lines with heterozygous or homozygous genotypes of the non-risk allele (T). Furthermore, the IC50 values of mafosfamide [Maf; active metabolite of cyclophosphamide (CY)] and cytarabine (AraC) tended to be associated with the genotype of rs4948488. Similar associations were observed in genotypes of the relapse-linked rs2893881 and rs6479778, but not in those of the susceptibility-linked rs7923074 and rs10821936. In addition, the IC50 values of methotrexate (MTX) were significantly higher (p = 0.023) in 36 cell lines with lower ARID5B gene expression (median IC50: 37.1 ng/ml) than those in the other 36 cell lines with higher expression (16.9 ng/ml). CONCLUSION: These observations in 72 BCP-ALL cell lines suggested that the risk allele of the relapse-linked SNPs of ARID5B may be involved in a higher relapse rate because of resistance to chemotherapeutic agents such as VCR, CY, and AraC. In addition, lower ARID5B gene expression may be associated with MTX resistance.
BACKGROUND: The genetic variants of the ARID5B gene have recently been reported to be associated with disease susceptibility and treatment outcome in childhood acute lymphoblastic leukemia (ALL). However, few studies have explored the association of ARID5B with sensitivities to chemotherapeutic agents. METHODS: We genotyped susceptibility-linked rs7923074 and rs10821936 as well as relapse-linked rs4948488, rs2893881, and rs6479778 of ARDI5B by direct sequencing of polymerase chain reaction (PCR) products in 72 B-cell precursor-ALL (BCP-ALL) cell lines established from Japanese patients. We also quantified their ARID5B expression levels by real-time reverse transcription PCR, and determined their 50% inhibitory concentration (IC50) values by alamarBlue assays in nine representative chemotherapeutic agents used for ALL treatment. RESULTS: No significant associations were observed in genotypes of the susceptibility-linked single nucleotide polymorphisms (SNPs) and the relapsed-linked SNPs with ARID5B gene expression levels. Of note, IC50 values of vincristine (VCR) (median IC50: 39.6 ng/ml) in 12 cell lines with homozygous genotype of risk allele (C) in the relapse-linked rs4948488 were significantly higher (p = 0.031 in Mann-Whitney U test) than those (1.04 ng/ml) in 60 cell lines with heterozygous or homozygous genotypes of the non-risk allele (T). Furthermore, the IC50 values of mafosfamide [Maf; active metabolite of cyclophosphamide (CY)] and cytarabine (AraC) tended to be associated with the genotype of rs4948488. Similar associations were observed in genotypes of the relapse-linked rs2893881 and rs6479778, but not in those of the susceptibility-linked rs7923074 and rs10821936. In addition, the IC50 values of methotrexate (MTX) were significantly higher (p = 0.023) in 36 cell lines with lower ARID5B gene expression (median IC50: 37.1 ng/ml) than those in the other 36 cell lines with higher expression (16.9 ng/ml). CONCLUSION: These observations in 72 BCP-ALL cell lines suggested that the risk allele of the relapse-linked SNPs of ARID5B may be involved in a higher relapse rate because of resistance to chemotherapeutic agents such as VCR, CY, and AraC. In addition, lower ARID5B gene expression may be associated with MTX resistance.
Entities:
Keywords:
ARID5B; B-cell precursor acute lymphoblastic leukemia; Drug sensitivities; Single nucleotide polymorphism
Authors: Heng Xu; Xujie Zhao; Deepa Bhojwani; Shuyu E; Charnise Goodings; Hui Zhang; Nita L Seibel; Wentao Yang; Chunliang Li; William L Carroll; William E Evans; Jun J Yang Journal: Clin Cancer Res Date: 2019-10-01 Impact factor: 12.531
Authors: Lisa R Treviño; Wenjian Yang; Deborah French; Stephen P Hunger; William L Carroll; Meenakshi Devidas; Cheryl Willman; Geoffrey Neale; James Downing; Susana C Raimondi; Ching-Hon Pui; William E Evans; Mary V Relling Journal: Nat Genet Date: 2009-08-16 Impact factor: 38.330
Authors: Jayaram Vijayakrishnan; Maoxiang Qian; James B Studd; Wenjian Yang; Ben Kinnersley; Philip J Law; Peter Broderick; Elizabeth A Raetz; James Allan; Ching-Hon Pui; Ajay Vora; William E Evans; Anthony Moorman; Allen Yeoh; Wentao Yang; Chunliang Li; Claus R Bartram; Charles G Mullighan; Martin Zimmerman; Stephen P Hunger; Martin Schrappe; Mary V Relling; Martin Stanulla; Mignon L Loh; Richard S Houlston; Jun J Yang Journal: Nat Commun Date: 2019-11-25 Impact factor: 14.919
Authors: Joseph L Wiemels; Kyle M Walsh; Adam J de Smith; Catherine Metayer; Semira Gonseth; Helen M Hansen; Stephen S Francis; Juhi Ojha; Ivan Smirnov; Lisa Barcellos; Xiaorong Xiao; Libby Morimoto; Roberta McKean-Cowdin; Rong Wang; Herbert Yu; Josephine Hoh; Andrew T DeWan; Xiaomei Ma Journal: Nat Commun Date: 2018-01-18 Impact factor: 17.694
Authors: Karla Beatriz Cardias Cereja Pantoja; Tereza Cristina de Brito Azevedo; Darlen Cardoso de Carvalho; Natasha Monte; Amanda de Nazaré Cohen Paes; Maria Clara da Costa Barros; Lui Wallacy Morikawa Souza Vinagre; Ana Rosa Sales de Freitas; Rommel Mario Rodríguez Burbano; Paulo Pimentel de Assumpção; Sidney Emanuel Batista Dos Santos; Marianne Rodrigues Fernandes; Ney Pereira Carneiro Dos Santos Journal: Genes (Basel) Date: 2022-02-10 Impact factor: 4.096