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Article Dans Une Revue Blood Advances Année : 2017

Genetic association with B-cell acute lymphoblastic leukemia in allogeneic transplant patients differs by age and sex

Alyssa Clay-Gilmour
  • Fonction : Auteur
Leah Preus
  • Fonction : Auteur
Kenan Onel
  • Fonction : Auteur
Andrew Skol
  • Fonction : Auteur
Eric Hungate
  • Fonction : Auteur
Loreall Pooler
  • Fonction : Auteur
Song Liu
  • Fonction : Auteur
KSU
Xiaochun Zhu
  • Fonction : Auteur
Annemarie Block
  • Fonction : Auteur
Sheila Sait
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Ezgi Karaesmen
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Abbas Rizvi
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Daniel Weisdorf
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Christine Ambrosone
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David Tritchler
  • Fonction : Auteur
Eva Ellinghaus
  • Fonction : Auteur
Marcelo Pasquini
  • Fonction : Auteur
Lara Sucheston-Campbell
  • Fonction : Auteur

Résumé

The incidence and mortality rates of B-cell acute lymphoblastic leukemia (B-ALL) differ by age and sex. To determine if inherited genetic susceptibility contributes to these differences we performed 2 genome-wide association studies (GWAS) by age, sex, and subtype and subsequent meta-analyses. The GWAS included 446 B-ALL cases, and 3027 healthy unrelated blood and marrow transplant (BMT) donors as controls from the Determining the Influence of Susceptibility Conveying Variants Related to One-Year Mortality after BMT (DISCOVeRY-BMT) study. We identified 1 novel variant, rs189434316, significantly associated with odds of normal cytogenetic B-ALL (odds ratio from meta-analysis [ORmeta] = 3.7; 95% confidence interval [CI], 2.5, 6.2; P value from meta-analysis [Pmeta] = 6.0 × 10-9). The previously reported pediatric B-ALL GWAS variant, rs11980379 (IKZF1), replicated in B-ALL pediatric patients (ORmeta = 2.3; 95% CI, 1.5, 3.7; Pmeta = 1.0 × 10-9), with evidence of heterogeneity (P = .02) between males and females. Sex differences in single-nucleotide polymorphism effect were seen in those >15 years (OR = 1.7; 95% CI, 1.4, 2.2, PMales = 6.38 × 10-6/OR = 1.1; 95% CI, 0.8, 1.5; PFemales = .6) but not ≤15 years (OR = 2.3; 95% CI, 1.4, 3.8; PMales = .0007/OR = 1.9; 95% CI, 1.2, 3.2; PFemales = .007). The latter association replicated in independent pediatric B-ALL cohorts. A previously identified adolescent and young-adult onset ALL-associated variant in GATA3 is associated with B-ALL risk in those >40 years. Our findings provide more evidence of the influence of genetics on B-ALL age of onset and we have shown the first evidence that IKZF1 associations with B-ALL may be sex and age specific.
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hal-04043240 , version 1 (23-03-2023)

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Alyssa Clay-Gilmour, Theresa Hahn, Leah Preus, Kenan Onel, Andrew Skol, et al.. Genetic association with B-cell acute lymphoblastic leukemia in allogeneic transplant patients differs by age and sex. Blood Advances, 2017, 1 (20), pp.1717-1728. ⟨10.1182/bloodadvances.2017006023⟩. ⟨hal-04043240⟩
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