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

Abstract Background High 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. Procedure Untreated bone marrow samples of 214 B-pALL patients were previously classified according to the modal numbers (iMN 8 ) 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. Results Data from 48 of the 53 HeH (iMN 8  > 50) B-pALL patients indicated that among the age, gender, WBC, and iMN 8 parameters, only the last was significantly associated with overall survival (pOS), which allowed the cases to be classified as iMN 8 51–54 (75%) and iMN 8 ≥ 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 iMN 8 was associated with a significantly reduced complexity of the subclonal landscape. However, iMN 8 did not prove to be an independent variable but was instead overridden by isolated trisomy of chromosome 4. Conclusions These 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.