Regional evaluation of childhood acute lymphoblastic leukemia genetic susceptibility loci among Japanese

Urayama, Kevin Y.; Takagi, Motoki; Kawaguchi, Takahisa; Matsuo, Keitaro; Tanaka, Yoïchi; Ayukawa, Yoko; Arakawa, Yuki; Hasegawa, Daisuke; Yuza, Yuki; Kaneko, Takashi; Noguchi, Yasushi; Taneyama, Yuichi; Ota, Setsuo; Inukai, Takeshi; Yanagimachi, Masakatsu; Keino, Dai; Koike, Kenichi; Toyama, Daisuke; Nakazawa, Yozo; Kurosawa, Hidemitsu; Nakamura, Kozue; Moriwaki, Koichi; Goto, Hiroaki; Sekinaka, Yujin; Morita, Daisuke; Kato, Motohiro; Takita, Junko; Tanaka, Toshihiro; Inazawa, Johji; Koh, Katsuyoshi; Ishida, Yasushi; Ohara, Akira; Mizutani, Shuki; Matsuda, Fumihiko; Manabe, Atsushi

doi:10.1038/s41598-017-19127-7

Cited by 25 publications

(26 citation statements)

References 42 publications

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“…F I G U R E 3 A, Odds ratios and 95% confidence intervals for SNPs identified from published GWAS literature in acute lymphoblastic leukemia (ALL) [38][39][40][41][42][43][44][45] and B, corresponding SNP allele frequencies from 1000 Genomes in ARID5B, IKZF1, CEBPE, CDKN2A/B, PIP4K2A, GATA3 among Asian and European populations [Color figure can be viewed at wileyonlinelibrary.com] of some cancer in adults eventually mirror those found in the general U.S. population. 50 It is unclear whether incidence rates of API regional groups are similar to those observed from the originating countries because of recent immigration to the U.S., such that their risk would still be reflective of their home country, or because of shared genetic predisposition between individuals with common countries of origin.…”

Section: Arid5b Ikzf1 Cebpe Cdkn1a/bpip4k2agata3mentioning

confidence: 99%

Childhood cancer incidence among specific Asian and Pacific Islander populations in the United States

Moore

Hubbard

Williams

et al. 2020

Intl Journal of Cancer

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Despite the vast genetic and environmental diversity in Asia, individuals of Asian and Pacific Islander (API) descent are often combined into a single group for epidemiologic analyses within the U.S. We used the Surveillance, Epidemiology and End Results (SEER) Detailed Asian/Pacific Islander Database to calculate incidence rates for discrete groups among children aged 0 to 19 years. Due to sample size constraints we pooled incidence among regional groups based on countries of origin: East Asians (Chinese, Japanese, Korean), Southeast (SE) Asians (Vietnamese, Laotian, Cambodian), Asian Indian/Pakistani, Oceanians (Guamanian, Samoan, Tongan) and Filipinos. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were calculated comparing each API regional group to Non-Hispanic Whites (NHW) and East Asians. Finally, we calculated the correlation between incidence of cancer in specific API ethnicities in SEER and in originating countries in the Cancer Incidence in Five Continents. Incidence rates among API regional groups varied. Acute lymphoblastic leukemia (ALL) was lower in children of SE Asian descent (IRR 0.65, 95% CI 0.44, 0.96) compared to NHW. Acute myeloid leukemia (AML) was more common among children from Oceania compared to NHW (IRR 3.88, 95% CI 1.83, 8.22). East Asians had higher incidence rates than SE Asians but lower rates compared to children from Oceania. Correlation of some incidence rates between US-based API ethnicities and originating countries were similar. The variation observed in childhood cancer incidence patterns among API groups may indicate differences in underlying genetics and/or patterns of exposure.

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Section: Arid5b Ikzf1 Cebpe Cdkn1a/bpip4k2agata3mentioning

confidence: 99%

Childhood cancer incidence among specific Asian and Pacific Islander populations in the United States

Moore

Hubbard

Williams

et al. 2020

Intl Journal of Cancer

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“…PIP4K2A was found to be essential for cell survival in AML (Jude et al, 2015) and several variant SNPs in the PIP4K2A locus have been associated with ALL susceptibility and leukemogenesis (Rosales-Rodríguez, et al, 2016;Urayama et al, 2018). We evaluated the sensitivity of a small panel of leukemia cell lines to THZ-P1-2, using a 72 h Cell-Titer Glo assay.…”

Section: Thz-p1-2 As a Probe For Potential Pi5p4k Dependencies In Cancermentioning

confidence: 99%

“…PIP4K2B-null mice were found to have increased insulin sensitivity and reduced adiposity (Lamia et al, 2004). PIP4K2A was found to be a dependency in AML and ALL (Jude et al, 2015;Rosales-Rodríguez, et al, 2016;Urayama et al, 2018) and PIP4K2A -/-, PIP4K2B +/-, TP53 -/mice had a dramatic tumor-free life extension compared to TP53 -/mice, uncovering a potential synthetic lethality of PI5P4K with p53 . Knockdown of PIP4K2A/B in human retinal pigment epithelial cells and rabbit models abrogated the pathogenesis of proliferative vitreoretinopathy (Ma et al, 2016).…”

Section: Introductionmentioning

confidence: 97%

Targeting the PI5P4K lipid kinase family in cancer using novel covalent inhibitors

Sivakumaren

Shim

Zhang

et al. 2019

Preprint

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The PI5P4Ks have been demonstrated to be important for cancer cell proliferation and other diseases. However, the therapeutic potential of targeting these kinases is understudied due to a lack of potent, specific small molecules available. Here we present the discovery and characterization of a novel pan-PI5P4K inhibitor, THZ-P1-2, that covalently targets cysteines on a disordered loop in PI5P4K//. THZ-P1-2 demonstrates cellular on-target engagement with limited off-targets across the kinome. AML/ALL cell lines were sensitive to THZ-P1-2, consistent with PI5P4K's reported role in leukemogenesis. THZ-P1-2 causes autophagosome clearance defects and upregulation in TFEB nuclear localization and target genes, disrupting autophagy in a covalent-dependent manner and phenocopying the effects of PI5P4K genetic deletion. Our studies demonstrate that PI5P4Ks are tractable targets, with THZ-P1-2 as a useful tool to further interrogate the therapeutic potential of PI5P4K inhibition and inform drug discovery campaigns for these lipid kinases in cancer metabolism and other autophagy-dependent disorders.

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“…rs7923074 and rs10821936; Fig. 1) are the most significant and recapitulated SNPs in various races, including Asian populations [7][8][9][10]. ARID5B belongs to the AT-rich interactive domain (ARID) family and acts as a transcription coactivator that binds to the 5′-AATA[CT]-3′ core sequence [11,12].…”

Section: Introductionmentioning

confidence: 99%

Association of relapse-linked ARID5B single nucleotide polymorphisms with drug resistance in B-cell precursor acute lymphoblastic leukemia cell lines

et al. 2020

Self Cite

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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.

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Regional evaluation of childhood acute lymphoblastic leukemia genetic susceptibility loci among Japanese

Abstract: Genome-wide association studies (GWAS) performed mostly in populations of

Cited by 25 publications

References 42 publications

Childhood cancer incidence among specific Asian and Pacific Islander populations in the United States

Childhood cancer incidence among specific Asian and Pacific Islander populations in the United States

Targeting the PI5P4K lipid kinase family in cancer using novel covalent inhibitors

Association of relapse-linked ARID5B single nucleotide polymorphisms with drug resistance in B-cell precursor acute lymphoblastic leukemia cell lines

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