Ramos-Muntada, MireiaTrincado, Juan L..Blanco, J. (Joan)Bueno, ClaraRodríguez Cortez, Virginia CarolinaBataller Torralba, AlexLopez Millan, Maria BelénSchwab, ClaireOrtega Blanco, MargaritaVelasco, PabloBlanco, Maria L.Nomdedéu Guinot, Josep FrancescRamírez-Orellana, ManuelMinguela, AlfredoFuster, José LuisCuatrecasas, EstherCamós Guijosa, MireiaBallerini, PaolaEscherich, GabrieleBoer, Judith M.Den Boer, Monique L.Hernández-Rivas, Jesús MaríaCalasanz, María JoséCazzaniga, GiovanniHarrison, Christine J.Menéndez, PabloMolina, Òscar2025-02-052025-02-052022-08-161574-7891https://hdl.handle.net/2445/218548B-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 < 0.0001 and 33.3% versus 80%, P < 0.0001, respectively. Moreover, longitudinal analysis of matched DX-REL HHD-B-ALL samples revealed distinct patterns of clonal evolution at relapse. Our study offers a reliable prognostic sub-stratification of pediatric MRD-negative HHD-B-ALL patients.21 p.application/pdfengcc-by (c) Ramos-Muntada, M. et al., 2022http://creativecommons.org/licenses/by/4.0/Anomalies cromosòmiquesInfantsFactors de risc en les malaltiesLeucèmiaChromosome abnormalitiesChildrenRisk factors in diseasesLeukemiainfo:eu-repo/semantics/article7527302025-02-05info:eu-repo/semantics/openAccess35726693