Abstract 4856: Sex differences in childhood leukemia genomics

Abstract Males have higher ALL and AML incidence and worse ALL survival using population-based data. Somatic genetics may play a role in ALL survival disparities and highlight potential sex specific treatment strategies for future study. Therefore, we evaluated sex differences in gene expression (RNA seq), copy number variation (CNV), and somatic mutation in ALL and AML. We stratified by cytogenomic subtypes in publicly available data from clinical cohorts using St. Jude PeCan (subtypes in Table 1). Then, we explored survival differences by sex within cytogenetic subtypes in publicly available data collected from Children’s Oncology Group patients in the NCI TARGET dataset (ALL n=387, 63% male; AML n=151, 51% male). Differentially expressed genes by sex were identified for ALL adjusting for subtype (n=214) and within subtypes (Table 1). There were no sex differentially expressed genes shared across subtypes and pathways identified from sex differentially expressed genes were few. In ETV6-RUNX1, there was as suggestion of worse 10-year survival for males (n=44, 61% male; Log-Rank p=0.068). Differentially expressed genes by sex were identified for AML adjusting for subtype (n=537) and within subtypes (Table 1). There were no differentially expressed genes by sex shared across AML subtypes. KMT2A had the highest number of pathways identified from sex differentially expressed genes (Table 1). There were no sex differences in AML survival. In ALL and AML subtypes there were no sex differences in CNVs (all t-test p>0.05) or somatic mutations (all Fisher’s Exact p>0.05). There were no sex differences in AML survival in TARGET, in agreement with population-based studies, and few differentially expressed genes identified in PeCan by subtypes. Sex differences in ALL survival were subtype specific and not heavily dependent on differentially expressed genes, CNVs, or somatic mutation. Sex differences in ALL survival may depend on treatment received, response to therapy, or other characteristics. Table 1. Select characteristics from leukemia cases PeCan ALL SubtypeTotal n=247, 58% male N (% male) Number of differentially expressed autosomal genes by sex (male-female expression) in PeCan Number of biologic pathways identified from differentially expressed genes (Reactome) BCR-ABL1 76 (68) 48 8 DUX4-IGH 54 (57) 218 0 ETV6-RUNX1 50 (52) 86 1 hyperdiploid 14 (64) 3,199 2 iAMP21 12 (50) 120 0 KMT2A 41 (51) 216 0 AML SubtypeTotal n=149, 51% male CBFB-MYH11 34 (55) 7 0 KMT2A 44 (50) 422 19 RUNX1-RUNX1T1 61 (46) 30 1 Citation Format: Lindsay A. Williams, Lauren J. Mills, Sofia Barragan, Peter M. Gordon, Jenny N. Poynter. Sex differences in childhood leukemia genomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4856.