[Analysis of Genetic Characteristics and Clinical Efficacy in Pediatric Acute Myeloid Leukemia with NUP98∷KDM5A Fusion Gene Positive].

OBJECTIVE

To explore the genetic characteristics and clinical efficacy of pediatric acute myeloid leukemia (AML) with NUP98∷KDM5A fusion gene positive.

METHODS

The laboratory and clinical characteristics of 10 NUP98∷KDM5A-positive pediatric AML patients identified by transcriptome sequencing (RNA-seq) were retrospectively analyzed during the period from March 2018 to March 2024 at Hebei Yanda Ludaopei Hospital and Beijing Ludaopei Hospital. Survival curves were plotted using the Kaplan-Meier method, and the 1-year overall survival and cumulative recurrence rates were calculated.

RESULTS

The median onset age of the 10 patients was 2(1-4) years, with a male to female ratio of 3∶7. All patients presented with thrombocytopenia, skin ecchymosis, and/or scattered petechiae as the main clinical manifestations. According to the FAB classification, 7 cases were diagnosed as AML-M7, 2 as AML-M5, and 1 as AML-M2. Cytogenetic analysis showed that 8 pediatric patients exhibited structural abnormalities involving chromosome 13 at initial diagnosis, relapse, or post-transplant relapse, and mainly manifested as del(13q). RNA-seq results showed that 9 patients had a fusion of NUP98 exon 13 with KDM5A exon 27, and 1 patient had a fusion of NUP98 exon 13 with KDM5A exon 25. Expression levels of MECOM and PRDM16 genes in the patient group were significantly higher than in the normal control group (P <0.05). Among co-occurring genetic mutations, JAK2 gene mutations exhibited the highest frequency of occurrence (40%). All patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), with 7 in complete remission (CR) and 3 in partial remission (PR)/non-remission (NR) before transplantation. The median follow-up time was 5.8 (2.5-23.7) months. During the follow-up period, 3 patients survived and 7 died, among which 6 died from relapse and 1 died from acute graft-versus-host disease of the gut post-transplantation. The median survival time post-transplantation was 7.8 months (95%CI : 0.8-14.8 months), the median relapse time was 5.5 months (95%CI : 0-11.7 months), the 1-year overall survival rate was 34.3%, and cumulative relapse rate was 55%.

CONCLUSION

Pediatric AML with the NUP98∷KDM5A fusion gene is more common in the M7 subtype, predominantly in females, and is often associated with chromosome 13 abnormalities and a higher rate of JAK2 mutations. Allo-HSCT can partially improve the prognosis of pediatric AML positive for NUP98∷KDM5A, but the relapse rate is high, and relapse is a significant factor affecting patient survival.