Higher Body Mass Index Is Associated with Differential Mutagenic Dependency in Acute Myeloid Leukemia

Background: Acute Myeloid Leukemia (AML) is associated with mutational diversity. Previous studies have shown that obesity has strong links to genomic instability directly through metabolic parameters, or indirectly through inflammation-mediated pathways, and is thereby strongly associated with canc...

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Veröffentlicht in:Blood 2020-11, Vol.136 (Supplement 1), p.38-40
Hauptverfasser: Shah, Shruti N., Rivero, Gustavo A.
Format: Artikel
Sprache:eng
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Zusammenfassung:Background: Acute Myeloid Leukemia (AML) is associated with mutational diversity. Previous studies have shown that obesity has strong links to genomic instability directly through metabolic parameters, or indirectly through inflammation-mediated pathways, and is thereby strongly associated with cancer initiation. Interestingly, obese patients have been reported to develop fewer mutations and have less dependence on “driver genes” like KRAS in favor of cell signaling alterations in colon cancer. Past work has also shown that transgenic mice have lower cholesterol levels and metabolism resembling the Warburg effect in the liver. We sought to find an association between RAS mutations and obesity in AML with aims to (1) find evidence of a “protective effect” of obesity against the acquisition of RAS (KRAS and NRAS) and (2) detect differential mutational expression among RAS-negative and RAS-positive AML to uncover possible tumor vulnerability. Methods: After IRB approval, 186 AML patients were screened from Baylor College of Medicine Institutions [Michael E. DeBakey VA Medical Center, and Baylor St. Luke's Medical Center]. 32 patients with next-generation sequencing (NGS) for myeloid mutations, complete blood count (CBC), body mass index (BMI), age, diabetes mellitus (DM), smoking, and lipid data were selected. Differential BMI was estimated by t-test in those with or without RAS mutations. A similar analysis was performed among patients with or without RAS mutations for relevant variables. The logistic regression model was used to independently assess the effect of BMI on RAS acquisition. All statistical analysis was performed using SAS software. Results: In our cohort, 22/32 [68.7%] and 10/32 [31.3%] patients had RAS-negative and RAS-positive AMLs, respectively. Differential expression for CBC and lipid profile [i.e. total, LDL, HDL-cholesterol, and triglycerides) in RAS-negative and RAS-positive AMLs are depicted in Table 1. BMI was higher for patients without RAS mutations than for patients with RAS mutations [30.7 vs. 25.8, p=0.0029]. No significant associations between DM and smoking were found with RAS-negative or RAS-positive AMLs. RAS-negative and RAS-positive patients were found to have similar levels of LDL, HDL, and TRG. A trend between RAS-negative and RAS-positive in terms of TC levels [173 vs. 191, p=0.12] was demonstrated. BMI was independently associated with differential leukemia RAS acquisition, p=0.04 [stepwise selection p
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2020-138564