Multiomic profiling identifies predictors of survival in African American patients with acute myeloid leukemia.

Autor: Stiff A; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA., Fornerod M; Department of Cell Biology, Erasmus Medical Center, Rotterdam, the Netherlands., Kain BN; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Nicolet D; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Alliance Statistics and Data Management Center, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Clara D. Bloomfield Center for Leukemia Outcomes Research, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA., Kelly BJ; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA., Miller KE; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA., Mrózek K; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Clara D. Bloomfield Center for Leukemia Outcomes Research, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA., Boateng I; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA., Bollas A; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA., Garfinkle EAR; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA., Momoh O; Department of Internal Medicine, Montefiore Health System/Albert Einstein College of Medicine, New York, NY, USA., Fasola FA; Department of Hematology, Faculty of Basic Medical Science, University of Ibadan, University College Hospital, Ibadan, Nigeria., Olawumi HO; Department of Haematology, University of Ilorin, Ilorin, Nigeria., Mencia-Trinchant N; Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA., Kloppers JF; School of Pathology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa.; National Health Laboratory Service, Universitas Academic Business Unit, Bloemfontein, South Africa., van Marle AC; School of Pathology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa.; National Health Laboratory Service, Universitas Academic Business Unit, Bloemfontein, South Africa., Hu E; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Department of Internal Medicine, University of Texas Southwestern, Dallas, TX, USA., Wijeratne S; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA., Wheeler G; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA., Walker CJ; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA., Buss J; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Clara D. Bloomfield Center for Leukemia Outcomes Research, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA., Heyrosa A; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Clara D. Bloomfield Center for Leukemia Outcomes Research, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA., Desai H; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Clara D. Bloomfield Center for Leukemia Outcomes Research, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA., Laganson A; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Clara D. Bloomfield Center for Leukemia Outcomes Research, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA., Hamp E; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Clara D. Bloomfield Center for Leukemia Outcomes Research, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA., Abu-Shihab Y; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Clara D. Bloomfield Center for Leukemia Outcomes Research, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA., Abaza H; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Clara D. Bloomfield Center for Leukemia Outcomes Research, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA., Kronen P; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA., Sen S; Divison of Biomedical Informatics, Cincinnati Children's Hospital, Cincinnati, OH, USA., Johnstone ME; Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA., Quinn K; Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA., Wronowski B; Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA., Hertlein E; Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA., Miles LA; Cancer and Blood Diseases Institute, Cincinnati Children's Hospital, Cincinnati, OH, USA., Mims AS; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA., Oakes CC; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA., Blachly JS; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA., Larkin KT; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA., Mundy-Bosse B; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA., Carroll AJ; Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA., Powell BL; Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC, USA., Kolitz JE; Monter Cancer Center, Hofstra Northwell School of Medicine, Lake Success, NY, USA., Stone RM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Duarte C; University of Colorado, Anschutz Medical Campus, College of Medicine, Denver, CO, USA., Abbott D; University of Colorado, Anschutz Medical Campus, College of Medicine, Denver, CO, USA., Amaya ML; University of Colorado, Anschutz Medical Campus, College of Medicine, Denver, CO, USA., Jordan CT; University of Colorado, Anschutz Medical Campus, College of Medicine, Denver, CO, USA., Uy GL; Washington University School of Medicine, Saint Louis, MO, USA., Stock W; University of Chicago, College of Medicine, Chicago, IL, USA., Archer KJ; Division of Biostatistics, College of Public Health, The Ohio State University, Columbus, OH, USA., Paskett ED; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Division of Cancer Prevention and Control, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA., Guzman ML; Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.; Sandra and Edward Meyer Cancer Center, New York, NY, USA., Levine RL; Memorial Sloan-Kettering Cancer Center, New York, NY, USA., Menghrajani K; Memorial Sloan-Kettering Cancer Center, New York, NY, USA., Chakravarty D; Memorial Sloan-Kettering Cancer Center, New York, NY, USA., Berger MF; Memorial Sloan-Kettering Cancer Center, New York, NY, USA., Bottomly D; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA., McWeeney SK; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA., Tyner JW; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA., Byrd JC; Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA., Salomonis N; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Grimes HL; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Mardis ER; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA. Elaine.Mardis@nationwidechildrens.org.; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA. Elaine.Mardis@nationwidechildrens.org., Eisfeld AK; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. Ann-Kathrin.Eisfeld@osumc.edu.; Alliance Statistics and Data Management Center, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. Ann-Kathrin.Eisfeld@osumc.edu.; Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. Ann-Kathrin.Eisfeld@osumc.edu.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2024 Oct 04. Date of Electronic Publication: 2024 Oct 04.
DOI: 10.1038/s41588-024-01929-x
Abstrakt: Genomic profiles and prognostic biomarkers in patients with acute myeloid leukemia (AML) from ancestry-diverse populations are underexplored. We analyzed the exomes and transcriptomes of 100 patients with AML with genomically confirmed African ancestry (Black; Alliance) and compared their somatic mutation frequencies with those of 323 self-reported white patients with AML, 55% of whom had genomically confirmed European ancestry (white; BeatAML). Here we find that 73% of 162 gene mutations recurrent in Black patients, including a hitherto unreported PHIP alteration detected in 7% of patients, were found in one white patient or not detected. Black patients with myelodysplasia-related AML were younger than white patients suggesting intrinsic and/or extrinsic dysplasia-causing stressors. On multivariable analyses of Black patients, NPM1 and NRAS mutations were associated with inferior disease-free and IDH1 and IDH2 mutations with reduced overall survival. Inflammatory profiles, cell type distributions and transcriptional profiles differed between Black and white patients with NPM1 mutations. Incorporation of ancestry-specific risk markers into the 2022 European LeukemiaNet genetic risk stratification changed risk group assignment for one-third of Black patients and improved their outcome prediction.
(© 2024. The Author(s).)
Databáze: MEDLINE
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