Abstract 6452: Role of obesity in regulation of acute myeloid leukemia progression

Abstract Acute myeloid leukemia (AML) accounts for 15-20 percent of childhood leukemia. Although improved treatment options have increased the overall survival for AML, approximately 30% of the cases tend to relapse. The management of AML patients is an ongoing challenge due to the relapse rates and treatment related mortality. Obesity is a leading cause of preventable death in the United States. Clinical outcome is linked to the degree of genetic heterogeneity of AML and higher body mass index (BMI) at diagnosis. As these underlying factors are associated with poor survival for AML, we are addressing the role and mechanism of obesity-associated factors in progression of AML in mouse models. Since obesity during pregnancy and childhood obesity may be associated with increased risk of developing AML, we tested the growth of the mouse AML cell line C1498 (ATCC.org) in the progeny of obesity-prone C57BL/6J db/db and ob/ob mice or normal (wild-type) C57BL/6J mice. Our data indicated that both ob/ob mice that lack leptin and db/db mice that lack the leptin receptor were prone to increased AML growth and showed significant increase in CD33-positive cells compared to wild-type C57BL/6J mice. Kaplan-Meier analysis of survival curves showed statistically significant differences between obese mice and wild type control C57BL/6J mice. Since obesity may change the immune phenotype and thereby affect AML growth, we performed blood cell immunophenotyping in C57BL/6J, db/db and ob/ob mice before C1498 engraft. We found that the T-cell numbers were significantly lower in the blood of db/db and ob/ob mice compared to the wild type control C57BL/6J mice. In contrast, myeloid-linage cell numbers were high in the blood of db/db and ob/ob mice than wild type C57BL/6J mice. The same pattern of immunophenotyping was found in post-AML blood as in pre-AML blood. Pearson Correlation analysis showed that survival of the mice positively correlated with the T-cell population and negatively correlated with myeloid population in blood. As diet-induced obesity (DIO) is the most common cause of obesity in humans, we used C57BL/6J mice that were fed with normal chow diet or high-fat diet (Research Diets, Inc., Catalog # D12492) and tested them for AML growth. Our data showed that obesity associated with high-fat diet also promoted AML growth with decreased survival when compared to normal chow-fed C57BL/6J mice. Taken together, our studies performed in mice with genetically driven obesity or high-fat diet induced obesity indicate that obesity promotes the growth of AML cells and is associated with decreased survival in mice. Our results suggest that T-cell and myeloid cell populations that are modulated by obesity may play an important role in AML progression. Citation Format: Jieyun Jiang, Samantha R. Melendez, Vivek M. Rangnekar. Role of obesity in regulation of acute myeloid leukemia progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6452.