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

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.

Untreated 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.

Data 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.

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.