Clonal heterogeneity and rates of specific chromosome gains are risk predictors in childhood high‐hyperdiploid B‐cell acute lymphoblastic leukemia

Autor: Mireia Ramos‐Muntada, Juan L. Trincado, Joan Blanco, Clara Bueno, Virginia C. Rodríguez‐Cortez, Alex Bataller, Belén López‐Millán, Claire Schwab, Margarita Ortega, Pablo Velasco, Maria L. Blanco, Josep Nomdedeu, Manuel Ramírez‐Orellana, Alfredo Minguela, Jose L. Fuster, Esther Cuatrecasas, Mireia Camós, Paola Ballerini, Gabriele Escherich, Judith Boer, Monique DenBoer, Jesús M. Hernández‐Rivas, Maria J. Calasanz, Giovanni Cazzaniga, Christine J. Harrison, Pablo Menéndez, Oscar Molina
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Molecular Oncology, Vol 16, Iss 16, Pp 2899-2919 (2022)
Druh dokumentu: article
ISSN: 1878-0261
1574-7891
DOI: 10.1002/1878-0261.13276
Popis: B‐cell acute lymphoblastic leukemia (B‐ALL) is the commonest childhood cancer. High hyperdiploidy (HHD) identifies the most frequent cytogenetic subgroup in childhood B‐ALL. Although hyperdiploidy represents an important prognostic factor in childhood B‐ALL, the specific chromosome gains with prognostic value in HHD‐B‐ALL remain controversial, and the current knowledge about the hierarchy of chromosome gains, clonal heterogeneity and chromosomal instability in HHD‐B‐ALL remains very limited. We applied automated sequential‐iFISH coupled with single‐cell computational modeling to identify the specific chromosomal gains of the eight typically gained chromosomes in a large cohort of 72 primary diagnostic (DX, n = 62) and matched relapse (REL, n = 10) samples from HHD‐B‐ALL patients with either favorable or unfavorable clinical outcome in order to characterize the clonal heterogeneity, specific chromosome gains and clonal evolution. Our data show a high degree of clonal heterogeneity and a hierarchical order of chromosome gains in DX samples of HHD‐B‐ALL. The rates of specific chromosome gains and clonal heterogeneity found in DX samples differ between HHD‐B‐ALL patients with favorable or unfavorable clinical outcome. In fact, our comprehensive analyses at DX using a computationally defined risk predictor revealed low levels of trisomies +18+10 and low levels of clonal heterogeneity as robust relapse risk factors in minimal residual disease (MRD)‐negative childhood HHD‐B‐ALL patients: relapse‐free survival beyond 5 years: 22.1% versus 87.9%, P
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