Genetic Landscape and Risk Stratification of AML With Hyperdiploid Karyotype

Hyperdiploid karyotype (HK) (49-65 chromosomes) in acute myeloid leukemia (AML) is rare. Recently, HK-AML with only numerical changes has been reclassified into an intermediate risk group in the updated 2022 European LeukemiaNet (ELN) risk classification, which has historically been classified into an adverse risk group. However, there are limited data in the literature concerning whether these new exclusion criteria are appropriate, and the genetic landscape of HK-AML remains unclear. We retrospectively analyzed a cohort of HK-AML diagnosed at our institution. Among 124 cases, 72 (58.1%) had concurrent adverse risk cytogenetic abnormalities (HK-ADV), 33 (26.6%) had other concurrent structural abnormalities (HK-STR) and 19 (15.3%) had numerical changes alone (HK-NUM). The most frequently gained chromosomes were chromosomes 8, 22, 21, and 19. TP53 mutation was associated with HK-ADV, and a higher frequency of mutations in DNA methylation genes was present in HK-NUM and HK-STR. Patients with HK-NUM had significantly longer overall survival (OS) and event-free survival (EFS) compared to those with HK-ADV. In the adjusted model accounting for confounders, the HK-STR outcome was superior to that of HK-ADV but was not significantly different from that of HK-NUM. In addition, patients with a modal chromosome number of 49-53 had more favorable survival than those with ≥ 54 chromosomes. Our data support the reclassification of HK-NUM patients in the intermediate risk group and suggest that HK-STR might also be more appropriately classified into the intermediate risk group.