Inherited GATA3 variants are associated with Ph-like childhood acute lymphoblastic leukemia and risk of relapse
Virginia Perez-Andreu,Kathryn G. Roberts,Richard C. Harvey,Wenjian Yang,Cheng Cheng,Deqing Pei,Heng Xu,Julie M. Gastier-Foster,Julie M. Gastier-Foster,Shuyu E,Joshua Yew Suang Lim,I. Ming Chen,Yiping Fan,Meenakshi Devidas,Michael J. Borowitz,Colton Smith,Geoffrey Neale,Esteban G. Burchard,Dara G. Torgerson,Federico Antillon Klussmann,Cesar Rolando Najera Villagran,Naomi J. Winick,Bruce M. Camitta,Elizabeth A. Raetz,Brent L. Wood,Feng Yue,William L. Carroll,Eric Larsen,W. Paul Bowman,Mignon L. Loh,Michael Dean,Deepa Bhojwani,Ching-Hon Pui,William E. Evans,Mary V. Relling,Stephen P. Hunger,Cheryl L. Willman,Charles G. Mullighan,Jun J. Yang +38 more
TLDR
In a genome-wide association study of 511 ALL cases and 6,661 non-ALL controls, a susceptibility locus for Ph-like ALL is identified and genotype at the GATA3 SNP was associated with early treatment response and risk of ALL relapse, providing insights into interactions between inherited and somatic variants and their role in ALL pathogenesis and prognosis.Abstract:
Recent genomic profiling of childhood acute lymphoblastic leukemia (ALL) identified a high-risk subtype with an expression signature resembling that of Philadelphia chromosome-positive ALL and poor prognosis (Ph-like ALL). However, the role of inherited genetic variation in Ph-like ALL pathogenesis remains unknown. In a genome-wide association study (GWAS) of 511 ALL cases and 6,661 non-ALL controls, we identified a susceptibility locus for Ph-like ALL (GATA3, rs3824662; P = 2.17 × 10(-14), odds ratio (OR) = 3.85 for Ph-like ALL versus non-ALL; P = 1.05 × 10(-8), OR = 3.25 for Ph-like ALL versus non-Ph-like ALL), with independent validation. The rs3824662 risk allele was associated with somatic lesions underlying Ph-like ALL (CRLF2 rearrangement, JAK gene mutation and IKZF1 deletion) and with variation in GATA3 expression. Finally, genotype at the GATA3 SNP was also associated with early treatment response and risk of ALL relapse. Our results provide insights into interactions between inherited and somatic variants and their role in ALL pathogenesis and prognosis.read more
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Noncoding genetic variation in GATA3 increases acute lymphoblastic leukemia risk through local and global changes in chromatin conformation
Hongbo Yang,Hui Zhang,Yuanyuan Luan,Tingting Liu,Wentao Yang,Kathryn G. Roberts,Maoxiang Qian,Bo Zhang,Wenjian Yang,Virginia Perez-Andreu,Jie Xu,Sriranga Iyyanki,Da Kuang,Lena Stasiak,Shalini C. Reshmi,Julie M. Gastier-Foster,Colton Smith,Ching-Hon Pui,William E. Evans,Stephen P. Hunger,Leonidas C. Platanias,Mary V. Relling,Charles G. Mullighan,Mignon L. Loh,Feng Yue,Jun Yang +25 more
TL;DR: In this paper , a key regulatory noncoding variant in GATA3 associated with childhood acute lymphoblastic leukemia (ALL) was identified through targeted sequencing in 5,008 patients.
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Towards precision medicine in childhood leukemia – Insights from mutationally activated cytokine receptor pathways in acute lymphoblastic leukemia
TL;DR: The recent discoveries of cytokine receptors and their signaling components in high risk leukemias and the potential approaches to target them are reviewed.
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Trends in Acute Lymphoblastic Leukemia Incidence in the United States by Race/Ethnicity From 2000 to 2016.
Qianxi Feng,Adam J. de Smith,Maria E. Vergara-Lluri,Ivo S. Muskens,Roberta McKean-Cowdin,Scott C. Kogan,Russell K. Brynes,Joseph L. Wiemels +7 more
TL;DR: In this paper, the authors used data from the Surveillance, Epidemiology, and End Results Registry to evaluate patterns in acute lymphoblastic leukemia (ALL) incidence from 2000 to 2016, including the association between percentage of people born in a foreign country at the county level and ALL incidence.
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Genomewide association study on monoclonal gammopathy of unknown significance (MGUS).
Hauke Thomsen,Chiara Campo,Niels Weinhold,Niels Weinhold,Miguel Inacio da Silva Filho,Luděk Pour,Evžen Gregora,Pavel Vodicka,Ludmila Vodickova,Per Hoffmann,Per Hoffmann,Markus M. Nöthen,Karl-Heinz Jöckel,Christian Langer,Roman Hájek,Hartmut Goldschmidt,Kari Hemminki,Kari Hemminki,Asta Försti,Asta Försti +19 more
TL;DR: To identify germ line variants contributing to the development of monoclonal gammopathy of undetermined significance (MGUS), an asymptomatic premalignant precursor for multiple myeloma (MM).
Journal ArticleDOI
Regulatory network of GATA3 in pediatric acute lymphoblastic leukemia
Qianqian Hou,Fei Liao,Shouyue Zhang,Duyu Zhang,Yan Zhang,Xueyan Zhou,Xuyang Xia,Yuanxin Ye,Hanshuo Yang,Zhaozhi Li,Leiming Wang,Xi Wang,Zhigui Ma,Yiping Zhu,Liang Ouyang,Y. Wang,Hui Zhang,Li Yang,Heng Xu,Yang Shu +19 more
TL;DR: The findings suggest that GATA3 may be involved in multiple tumor-related pathways (e.g., STAT/JAK pathway) in B-ALL to impact leukemogenesis through epigenetic regulation.
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