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

person Maha AT Elsebaie John H. Stroger, Jr. Hospital of Cook County, Chicago, IL info_outline Maha AT Elsebaie, Ekrem Turk, Vaishali Deenadayalan, Khaldun Obeidat, Ahmad Nanaa, Maryam Zia, Noah W. Birch

Authors person Maha AT Elsebaie John H. Stroger, Jr. Hospital of Cook County, Chicago, IL info_outline Maha AT Elsebaie, Ekrem Turk, Vaishali Deenadayalan, Khaldun Obeidat, Ahmad Nanaa, Maryam Zia, Noah W. Birch Organizations John H. Stroger, Jr. Hospital of Cook County, Chicago, IL Abstract Disclosures Research Funding No funding received None. 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. Distribution of mutations by diagnosis. AML & MDS MDS/MPN MPN p -value ASXL1 Mut 10 3 8 0.483 TET2 Mut 5 3 3 0.040 SRSF2 Mut 5 5 1 0.001 RUNX1 Mut 6 2 0 0.009 TP53 Mut 8 0 0 0.011 IDH2 Mut 6 0 0 0.035 FLT3 Mut 5 0 0 0.131