1. Obesity is a risk factor for acute promyelocytic leukemia: evidence from population and cross-sectional studies and correlation with FLT3 mutations and polyunsaturated fatty acid metabolism
- Author
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Edoardo Botteri, Massimo Breccia, Vincenzo Bagnardi, Teresa Bernal, Pau Montesinos, Pier Giuseppe Pelicci, Luca Mazzarella, Timothy J. Ley, Davide Di Salvatore, Cristina Gil, Krishnan Bhaskaran, Francesco Lo Coco, Miguel A. Sanz, Elena Gatti, Anthony Matthews, Mazzarella, L, Botteri, E, Matthews, A, Gatti, E, Di Salvatore, D, Bagnardi, V, Breccia, M, Montesinos, P, Bernal, T, Gil, C, Ley, T, Sanz, M, Bhaskaran, K, Lo Coco, F, and Pelicci, P
- Subjects
Acute promyelocytic leukemia ,Oncology ,Acute Myeloid Leukemia ,medicine.medical_specialty ,Myeloid ,Population ,Acute Promyelocytic Leukemia ,03 medical and health sciences ,0302 clinical medicine ,Leukemia, Promyelocytic, Acute ,Risk Factors ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Humans ,Obesity ,Clinical and Molecular Epidemiology ,education ,Settore MED/04 - Patologia Generale ,chemistry.chemical_classification ,education.field_of_study ,Cytogenetics and Molecular Genetics ,business.industry ,Hazard ratio ,Hematology ,Odds ratio ,Articles ,medicine.disease ,Leukemia ,medicine.anatomical_structure ,Cross-Sectional Studies ,chemistry ,Italy ,fms-Like Tyrosine Kinase 3 ,Spain ,Mutation ,business ,Body mass index ,030215 immunology ,Polyunsaturated fatty acid - Abstract
Obesity correlates with hematologic malignancies including leukemias, but risk of specific leukemia subtypes like acute promyelocytic leukemia and underlying molecular mechanisms are poorly understood. We explored multiple datasets for correlation between leukemia, body mass index (BMI) and molecular features. In a population-based study (n=5.2 million), we correlated BMI with promyelocytic leukemia, and other acute myeloid, lymphoid or other leukemias. In cross-sectional studies, we tested BMI deviation in promyelocytic leukemia trial cohorts from that expected based on national surveys. We explored The Cancer Genome Atlas for transcriptional signatures and mutations enriched in promyelocytic leukemia and/or obesity, and confirmed a correlation between body mass and FLT3 mutations in promyelocytic leukemia cohorts by logistic regression. In the population-based study, hazard ratio per 5 kg/m2 increase was: promyelocytic leukemia 1.44 (95%CI: 1.0-2.08), non-promyelocytic acute myeloid leukemias 1.17 (95%CI: 1.10-1.26), lymphoid leukemias 1.04 (95%CI: 1.0-1.09), other 1.10 (95%CI: 1.04-1.15). In cross-sectional studies, body mass deviated significantly from that expected (Italy: P
- Published
- 2020