Multiomic profiling identifies predictors of survival in African American patients with acute myeloid leukemia Journal Article
| Authors: | Stiff, A.; Fornerod, M.; Kain, B. N.; Nicolet, D.; Kelly, B. J.; Miller, K. E.; Mrózek, K.; Boateng, I.; Bollas, A.; Garfinkle, E. A. R.; Momoh, O.; Fasola, F. A.; Olawumi, H. O.; Mencia-Trinchant, N.; Kloppers, J. F.; van Marle, A. C.; Hu, E.; Wijeratne, S.; Wheeler, G.; Walker, C. J.; Buss, J.; Heyrosa, A.; Desai, H.; Laganson, A.; Hamp, E.; Abu-Shihab, Y.; Abaza, H.; Kronen, P.; Sen, S.; Johnstone, M. E.; Quinn, K.; Wronowski, B.; Hertlein, E.; Miles, L. A.; Mims, A. S.; Oakes, C. C.; Blachly, J. S.; Larkin, K. T.; Mundy-Bosse, B.; Carroll, A. J.; Powell, B. L.; Kolitz, J. E.; Stone, R. M.; Duarte, C.; Abbott, D.; Amaya, M. L.; Jordan, C. T.; Uy, G. L.; Stock, W.; Archer, K. J.; Paskett, E. D.; Guzman, M. L.; Levine, R. L.; Menghrajani, K.; Chakravarty, D.; Berger, M. F.; Bottomly, D.; McWeeney, S. K.; Tyner, J. W.; Byrd, J. C.; Salomonis, N.; Grimes, H. L.; Mardis, E. R.; Eisfeld, A. K. |
| Article Title: | Multiomic profiling identifies predictors of survival in African American patients with acute myeloid leukemia |
| Abstract: | 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. © The Author(s) 2024. |
| Keywords: | adult; cancer survival; aged; middle aged; major clinical study; overall survival; somatic mutation; genetics; mutation; leukemia, myeloid, acute; mortality; cytarabine; gene expression profiling; nuclear protein; etoposide; membrane proteins; cyclophosphamide; tumor marker; nuclear proteins; myelodysplastic syndrome; membrane protein; mitoxantrone; mutation rate; transcriptome; african american; induction chemotherapy; caucasian; gtp phosphohydrolases; isocitrate dehydrogenase; isocitrate dehydrogenase 1; guanosine triphosphatase; oncogene n ras; nucleophosmin; diaziquone; acute myeloid leukemia; exome; consolidation chemotherapy; isocitrate dehydrogenase 2; idh1 protein, human; humans; prognosis; human; male; female; article; nras protein, human; biomarkers, tumor; multiomics; black or african american; white people; npm1 protein, human; idh2 protein, human |
| Journal Title: | Nature Genetics |
| Volume: | 56 |
| Issue: | 11 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-11-01 |
| Start Page: | 2434 |
| End Page: | 2446 |
| Language: | English |
| DOI: | 10.1038/s41588-024-01929-x |
| PUBMED: | 39367245 |
| PROVIDER: | scopus |
| PMCID: | PMC11549055 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Source: Scopus |
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