Unveiling the Genetic and Clinical Differences of Acute Myeloid Leukemia (AML) in Obese Patients

Background: The molecular architecture of acute myeloid leukemia (AML) is heterogeneous. Obesity has been identified as a risk factor for the development of AML. There remains a scarcity of data elucidating the specific genetic profile of AML in obese patients. Methods: We conducted a review of adult patients treated at our institution for newly diagnosed AML from January 1, 2017, to January 1, 2023. Obesity is defined as BMI > 30 kg/m². Demographic, clinical, laboratory, and pathologic data were collected retrospectively. The primary outcome of interest was the molecular features of obese compared to non-obese AML patients. The secondary outcome was overall survival (OS). Inverse probability of treatment weights (IPTW) used to balance both groups on several confounding variables. Results: A total of 185 patients were included in the analysis. 90 (49%) were obese. Compared with non-obese patients, obese patients were younger and more likely to be females (55 vs. 63, p = 0.04, 55% vs. 38%, p value, p = 0.02, respectively). After matching on age, gender, and ethnicity, obese patients exhibit lower rates of total number of gene mutations (median 2.7 vs. 3.2, p = 0.05), significantly lower rates of mutations in transcriptional factor genes (15.7% vs. 33.2%, p = 0.01), and near-significant in spliceosome genes (12% vs. 22.3%, p = 0.08), and higher rates of NPM1 mutation (23.3% vs. 12.6%, p = 0.08). Median OS was not significantly different in the matched cohort. Conclusions: The molecular features of obese AML patients significantly differ from non-obese counterparts. These findings suggest distinct underlying mechanisms in leukemogenesis in obese patients.