Bahrami Hezaveh Ehsan, Yan Jiong, Zhao Davidson, Wangulu Collins, Lo Winnie, Wei Cuihong, Chang Hong
Department of Laboratory Hematology, University Health Network, Toronto, Ontario, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Eur J Haematol. 2025 Aug;115(2):165-175. doi: 10.1111/ejh.14434. Epub 2025 May 12.
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.
急性髓系白血病（AML）中的超二倍体核型（HK）（49 - 65条染色体）较为罕见。最近，在2022年更新的欧洲白血病网络（ELN）风险分类中，仅存在数目改变的HK-AML已被重新分类为中危组，而在历史上它被归为高危组。然而，关于这些新的排除标准是否合适，文献中的数据有限，并且HK-AML的基因图谱仍不清楚。我们对在本机构诊断的一组HK-AML患者进行了回顾性分析。在124例病例中，72例（58.1%）同时存在不良风险细胞遗传学异常（HK-ADV），33例（26.6%）存在其他同时发生的结构异常（HK-STR），19例（15.3%）仅存在数目改变（HK-NUM）。最常获得的染色体是8号、22号、21号和19号染色体。TP53突变与HK-ADV相关，并且HK-NUM和HK-STR中DNA甲基化基因的突变频率更高。与HK-ADV患者相比，HK-NUM患者的总生存期（OS）和无事件生存期（EFS）显著更长。在考虑混杂因素的校正模型中，HK-STR的预后优于HK-ADV，但与HK-NUM没有显著差异。此外，核型数为49 - 53的患者比核型数≥54的患者生存期更优。我们的数据支持将HK-NUM患者重新分类为中危组，并表明HK-STR也可能更适合归为中危组。
