Conserved hierarchical gain of chromosome 4 is an independent prognostic factor in high hyperdiploid pediatric acute lymphoblastic leukemia

•8 chromosomes defined modal number by iFISH can prognostically stratify B-pALL.•Modal number of ≥ 55 relates significantly to better outcome of hyperdiploid B-pALL.•Hyperdiploid B-pALL with ≥ 55 chromosomes reveals less complex subclonal landscape.•Highly conserved chromosomal gain is a unique feature of high hyperdiploid B-pALL.•Conserved hierarchical gain of chromosome 4 is an independent prognostic factor.

BackgroundHigh hyperdiploid (HeH) pre-B pediatric acute lymphoblastic leukemia (B-pALL) is known to be heterogeneous by prognosis, but the stratification principals according to conventional cytogenetic analysis (CCA) are equivocal.ProcedureUntreated bone marrow samples of 214 B-pALL patients were previously classified according to the modal numbers (iMN8) based on the gains of the chromosomes 4, 6, 10, 14, 17, 18, 21, and X as revealed by consecutive and correlated 2 × 4 color interphase fluorescence in situ hybridization, and at least five years of follow up data were analyzed.ResultsData from 48 of the 53 HeH (iMN8 > 50) B-pALL patients indicated that among the age, gender, WBC, and iMN8 parameters, only the last was significantly associated with overall survival (pOS), which allowed the cases to be classified as iMN8 51-54 (75%) and iMN8 ≥ 55 (95%). Among the specific chromosomal gains of +4, +4/ + 6, +4/ + 17 and +4/ + 18, the first exhibited the most significance in terms of beneficial outcomes. The better prognostic group according to the iMN8 was associated with a significantly reduced complexity of the subclonal landscape. However, iMN8 did not prove to be an independent variable but was instead overridden by isolated trisomy of chromosome 4.ConclusionsThese data indicate that the better outcomes in the HeH B-pALL group arose from the gain of a specific chromosome that always ranks at the same position in the sequential acquisition of the affected chromosomes.