1. Copy Number Alterations are Associated with the Risk of Very Early Relapse in Pediatric B-lineage Acute Lymphoblastic Leukemia: A Nested Case-control MIGICCL Study
- Author
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José Refugio Torres-Nava, Vilma Carolina Bekker-Méndez, Karina Anastacia Solís-Labastida, Raquel Amador-Sánchez, Mónica Patricia Ortiz-Maganda, Omar Alejandro Sepúlveda-Robles, Alma Gurrola-Silva, Minerva Mata-Rocha, Janet Flores-Lujano, Martha Margarita Velázquez-Aviña, Haydeé Rosas-Vargas, Juan Carlos Núñez-Enríquez, María Luisa Pérez-Saldivar, Silvia Jiménez-Morales, José Gabriel Peñaloza-González, Luz Victoria Flores-Villegas, Elva Jiménez-Hernández, Jorge Alfonso Martín-Trejo, Juan Manuel Mejía-Aranguré, Rosa Martha Espinosa-Elizondo, Javier Gaytan-Cervantes, Carolina Gonzalez-Torres, María Raquel Miranda-Madrazo, David Aldebarán Duarte-Rodríguez, Ana Claudia Velázquez-Wong, Darío Orozco-Ruiz, Jessica Denise Santillán-Juárez, Beatriz Rosales-Rodríguez, Maria de los Angeles del Campo-Martinez, and Aurora Medina-Sanson
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Multivariate statistics ,DNA Copy Number Variations ,Population ,03 medical and health sciences ,0302 clinical medicine ,CDKN2A ,Recurrence ,Internal medicine ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,medicine ,Humans ,Multiplex ligation-dependent probe amplification ,education ,Child ,education.field_of_study ,Proportional hazards model ,business.industry ,Univariate ,General Medicine ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Prognosis ,030104 developmental biology ,030220 oncology & carcinogenesis ,Case-Control Studies ,Cohort ,Nested case-control study ,business ,Gene Deletion - Abstract
Background Refining risk stratification to avoid very early relapses (VER) in Mexican patients with B-lineage acute lymphoblastic leukemia (B-ALL) could lead to better survival rates in our population. Aim of the study The purpose of this study was to investigate the association between the United Kingdom ALL (UKALL)-CNA classifier and VER risk in Mexican patients with childhood B-ALL. Methods A nested case-control study of 25 cases with VER and 38 frequency-matched controls without relapse was conducted within the MIGICCL study cohort. They were grouped into the categories of the UKALL-CNA risk classifier (good [reference], intermediate and poor), according to the results obtained by multiplex ligation dependent probe amplification. Overall and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards analyses were conducted. Results The CDKN2A/B genes were most frequently deleted in the group with relapse. According to UKALL-CNA classifier, 33 (52.4%) patients were classified as good, 21 (33.3%) intermediate and 9 (14.3%) poor-risk B-ALL. The intermediate and poor risk groups were associated with an increased risk of VER (HR = 4.94, 95% CI = 1.87–13.07 and HR = 7.42, 95% CI = 2.37–23.26, respectively) in comparison to the good-risk patients. After adjusting by NCI risk classification and chemotherapy scheme in a multivariate model, the risks remained significant. Conclusions Our data support the clinical utility of profiling CNAs to potentially refine current risk stratification strategies of patients with B-ALL.
- Published
- 2020