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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Impact of Insurance Status on Survival Outcomes in Adults With Acute Lymphoblastic Leukemia (ALL): A Single-center Experience.
Rebecca Krakora,Weichung Shih,Pallvi Popli,Elan Gorshein,Gratian Salaru,Dirk F. Moore,Chunxia Chen,Kevin A. David,Rajat Bannerji +8 more
TL;DR: Adult patients with ALL without health insurance at time of diagnosis had worse PFS when controlling for other relevant clinical factors, and lack of insurance may be an obstacle to timely, effective maintenance therapy in the outpatient setting.
Posted ContentDOI
Non-coding germline GATA3 variants alter chromatin topology and contribute to pathogenesis of acute lymphoblastic leukemia
Hongbo Yang,Hui Zhang,Yu Luan,Tingting Liu,Kathryn G. Roberts,Maoxiang Qian,Bo Zhang,Wenjian Yang,Virginia Perez-Andreu,Jie Xu,Sriranga Iyyanki,Da Kuang,Shalini C. Reshmi,Shalini C. Reshmi,Julie M. Gastier-Foster,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: Evidence is provided for a novel mechanism by which a germline non-coding variant contributes to oncogene activation epigenetic regulation and 3D genome reprogramming.
Journal ArticleDOI
Poverty and Survival in Childhood Cancer: A Framework to Move Toward Systemic Change
Journal ArticleDOI
Have any strategies in Ph-like ALL been shown to be effective?
Ibrahim Aldoss,Anjali S. Advani +1 more
TL;DR: In this paper, the authors show that the high relapse rate in patients with Ph-like ALL does not necessary correlate with early minimal residual disease (MRD) response, raising the question of consolidation with allogenic HCT in all adults with PH-like acute lymphoblastic leukemia in first complete remission irrespective of MRD response.
Journal ArticleDOI
Outcomes of allogeneic hematopoietic cell transplantation in adults with fusions associated with Ph-like ALL
Ibrahim Aldoss,Dongyun Yang,Vanina Tomasian,Sally Mokhtari,Ryan Jackson,Zhaohui Xu,Milhan Telatar,Hooi Yew,Monzr M. Al Malki,Amandeep Salhotra,Samer K. Khaled,Haris Ali,Ahmed Aribi,Karamjeet S. Sandhu,Matthew Mei,Shukaib Arslan,Paul Koller,Andrew S. Artz,Patricia Aoun,Dongqing Gu,David S. Snyder,F. Stewart,Peter T. Curtin,Anthony S. Stein,Raju Pillai,Guido Marcucci,Stephen J. Forman,Vinod Pullarkat,Ryotaro Nakamura,Michelle Afkhami +29 more
TL;DR: It is suggested that alloHCT consolidation results in similarly favorable survival outcomes in adult patients with Ph-like fusions and other high-risk B-cell ALL.
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