A step toward genomic equity: Mutational profiling of patients with myeloid neoplasm in the largest minority-serving hospital in metropolitan Chicago.

Abstract

7037 Background: Information on genomic landscape of myeloid neoplasms comes from large studies of patients with predominantly European ancestry. Minority-serving hospitals offer unique opportunities to study ethnically diverse populations. Methods: In this retrospective study at the Stroger Hospital of Cook County, we included patients ≥18 years old with myeloid neoplasms or premalignant conditions who underwent mutational profiling via next generation sequencing (NGS). We utilized two commercially available myeloid panels: “ FoundationOneHeme” (406 gene panel) and “ Tempus” (648 gene panel) . Patient demographics were collected, including self-reported race/ethnicity. We compared data distribution using Kruskal-Wallis, Pearson’s χ2, or Fisher’s exact tests. Overall survival (OS) probabilities were compared using the log-rank test. Results: Ninety-four patients underwent NGS between 04/01/2020 and 12/31/2022, including 45 females (47.9%). 38 patients (40.4%) identified as Black, 28 (29.8%) as White, and 28 (29.8%) as Other (10.6% Asian, 9.6% Mexican/South American, and 9.6% undetermined). 30 patients (32%) identified as Hispanic and 64 (68%) as Non-Hispanic. Diagnoses included Acute myeloid leukemia (AML, 32%), Myelodysplastic syndromes (MDS, 13%), MDS/MPN overlap syndrome (7%), and Clonal Hematopoiesis of Indeterminate Potential (7%). Eighty-eight patients had at least one pathogenic variant and harbored 259 mutations in 74 genes. Commonly mutated genes were ASXL1 (23%), JAK2 (17%), DNMT3A (14%), and TET2 (13%).Non-White patients were more likely to have IDH2 mutations (5% Black vs. 0% White vs. vs. 14% Other races, p=0.011). Mutation count didn’t differ between racial p=0.525 or ethnic groups p=0.345. AML & MDS patients were more likely to have TET2, RUNX1, TP53, and IDH2 mutations. In addition, 24% of AML & MDS patients had mutated ASXL1. TET2, SRSF2, and RUNX1 mutations were common among MDS/MPN patients (Table). AML & MDS patients had poor OS, but OS didn’t differ between racial/ethnic groups. Conclusions: Premalignant mutations (e.g., ASXL1, TET2) predominated in our patients and tended to co-occur, increasing the overall mutational burden. Non-White patients were more likely to have IDH2 mutations. Adverse markers were common among AML & MDS patients, likely contributing to their dismal survival. Studies inclusive of ethnically diverse patients are needed to accurately translate genetic findings into clinical practice. This report from a large, minority-serving hospital represents a step toward promoting genomic and healthcare equity. [Table: see text]