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
Luca Mazzarella,
Edoardo Botteri,
Anthony Matthews,
Elena Gatti,
Davide Di Salvatore,
Vincenzo Bagnardi,
Massimo Breccia,
Pau Montesinos,
Teresa Bernal,
Cristina Gil,
Timothy J Ley,
Miguel Sanz,
Krishnan Bhaskaran,
Francesco Lo Coco,
Pier Giuseppe Pelicci
Affiliations
Luca Mazzarella
Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy;Division of Early Drug Development for Innovative Therapies, European Institute of Oncology IRCCS, Milan, Italy
Edoardo Botteri
Cancer Registry of Norway, Oslo, Norway
Anthony Matthews
London School of Hygiene and Tropical Medicine, London, UK
Elena Gatti
Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy
Davide Di Salvatore
IFOM-FIRC Institute of Molecular Oncology, Milan, Italy
Vincenzo Bagnardi
University of Milan-Bicocca, Milan, Italy
Massimo Breccia
Division of Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy
Pau Montesinos
Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain
Teresa Bernal
Hospital Central de Asturias, Oviedo, Spain
Cristina Gil
Hospital General, Alicante, Spain
Timothy J Ley
Department of Medicine, Division of Oncology, Washington University in St. Louis, Saint Louis, MO, USA
Miguel Sanz
Hematology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain
Krishnan Bhaskaran
London School of Hygiene and Tropical Medicine, London, UK
Francesco Lo Coco
Department of Hematology, University Tor Vergata, Roma, Italy
Pier Giuseppe Pelicci
Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy;Department of Oncology and Hemato-Oncology, University of Milan
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
