Prediction of acute myeloid leukaemia risk in healthy individuals
| Autor: | Aurelio Barricarte, Claire Hardy, Kristian M. Bowles, Abigail Britten, Mattias Johansson, Sabina Sieri, Kay-Tee Khaw, Sagi Abelson, Philip A. Beer, Stanley W.K. Ng, Matthieu Foll, Lee Timms, Diana Hoult, Salvatore Panico, Shabina Hayat, Elena Salamanca-Fernández, Paul M. Krzyzanowski, Rosario Tumino, Noam Barda, José María Huerta, Lawrence E. Heisler, Jean C.Y. Wang, Inigo Martincorena, Mark D. Minden, Robert Luben, John E. Dick, Trevor J. Pugh, Sam Behjati, Anna Karakatsani, Philip Awadalla, Carlo La Vecchia, Zhen Zhao, Ruth C. Travis, Iulia Cirlan, Omer Weissbrod, Giovanna Masala, Heiner Boeing, Rui Costa, Elio Riboli, Nicholas J. Wareham, Calli Latimer, Philip C. Zuzarte, David T. Jones, Ting Ting Wang, J. Ramón Quirós, Grace Collord, Peter J. Campbell, Roel Vermeulen, Yogi Sundaravadanam, Elli Papaemmanuil, Antonia Trichopoulou, Ran D. Balicer, James McKay, Alwin Krämer, Jessica Miller, Keiran Raine, Jenna Eagles, Paolo Vineis, Netta Mendelson Cohen, Silvia Polidoro, Scott V. Bratman, Amos Tanay, Moritz Gerstung, George S. Vassiliou, Paul Brennan, Eran Segal, Karen Ng, Rudolf Kaaks, Núria Sala, David Soave, Faridah Mbabaali, Danielle Pasternack, Liran I. Shlush, John Douglas Mcpherson, Elisabeth Niemeyer |
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| Přispěvatelé: | One Health Chemisch, dIRAS RA-2, Abelson, Sagi, Collord, Grace, Ng, Stanley W K, Weissbrod, Omer, Mendelson Cohen, Netta, Niemeyer, Elisabeth, Barda, Noam, Zuzarte, Philip C, Heisler, Lawrence, Sundaravadanam, Yogi, Luben, Robert, Hayat, Shabina, Wang, Ting Ting, Zhao, Zhen, Cirlan, Iulia, Pugh, Trevor J, Soave, David, Ng, Karen, Latimer, Calli, Hardy, Claire, Raine, Keiran, Jones, David, Hoult, Diana, Britten, Abigail, Mcpherson, John D, Johansson, Mattia, Mbabaali, Faridah, Eagles, Jenna, Miller, Jessica K, Pasternack, Danielle, Timms, Lee, Krzyzanowski, Paul, Awadalla, Philip, Costa, Rui, Segal, Eran, Bratman, Scott V, Beer, Philip, Behjati, Sam, Martincorena, Inigo, Wang, Jean C Y, Bowles, Kristian M, Quirós, J Ramón, Karakatsani, Anna, La Vecchia, Carlo, Trichopoulou, Antonia, Salamanca-Fernández, Elena, Huerta, José M, Barricarte, Aurelio, Travis, Ruth C, Tumino, Rosario, Masala, Giovanna, Boeing, Heiner, Panico, Salvatore, Kaaks, Rudolf, Krämer, Alwin, Sieri, Sabina, Riboli, Elio, Vineis, Paolo, Foll, Matthieu, Mckay, Jame, Polidoro, Silvia, Sala, Núria, Khaw, Kay-Tee, Vermeulen, Roel, Campbell, Peter J, Papaemmanuil, Elli, Minden, Mark D, Tanay, Amo, Balicer, Ran D, Wareham, Nicholas J, Gerstung, Moritz, Dick, John E, Brennan, Paul, Vassiliou, George S, Shlush, Liran I, Italian Institute for Genomic Medicine IIGM, Collord, Grace [0000-0003-1924-4411], Luben, Robert [0000-0002-5088-6343], Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Vassiliou, George [0000-0003-4337-8022], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology Myeloid Male 0302 clinical medicine Models hemic and lymphatic diseases Prevalence 2.1 Biological and endogenous factors Electronic Health Records Aetiology Cells Cultured Cancer Pediatric screening and diagnosis Multidisciplinary Leukemia Incidence (epidemiology) Age Factors CLONAL HEMATOPOIESIS Hematology Middle Aged CANCER 3. Good health Multidisciplinary Sciences Haematopoiesis Detection Leukemia Myeloid Acute medicine.anatomical_structure Myeloid leukemia Health 030220 oncology & carcinogenesis Cohort Disease Progression Science & Technology - Other Topics Female Adult medicine.medical_specialty Pediatric Cancer Childhood Leukemia General Science & Technology Leucèmia mieloide MODELS Acute Risk Assessment CLASSIFICATION Article 03 medical and health sciences Rare Diseases Genetic Cancer stem cell Internal medicine MD Multidisciplinary medicine Genetics Mortalitat Humans Genetic Predisposition to Disease Progenitor cell Mortality neoplasms Aged Science & Technology Models Genetic business.industry Prevention SOMATIC MUTATIONS medicine.disease EVOLUTION Hematopoiesis 4.1 Discovery and preclinical testing of markers and technologies 030104 developmental biology Good Health and Well Being Mutagenesis Mutation PATTERNS Bone marrow business |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Nature Nature, vol 559, iss 7714 Nature, 559(7714), 400. Nature Research |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | The incidence of acute myeloid leukaemia (AML) increases with age and mortality exceeds 90% when diagnosed after age 65. Most cases arise without any detectable early symptoms and patients usually present with the acute complications of bone marrow failure(1). The onset of such de novo AML cases is typically preceded by the accumulation of somatic mutations in preleukaemic haematopoietic stem and progenitor cells (HSPCs) that undergo clonal expansion(2,3). However, recurrent AML mutations also accumulate in HSPCs during ageing of healthy individuals who do not develop AML, a phenomenon referred to as age-related clonal haematopoiesis (ARCH)(4-8). Here we use deep sequencing to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH. We analysed peripheral blood cells from 95 individuals that were obtained on average 6.3 years before AML diagnosis (pre-AML group), together with 414 unselected age- and gender-matched individuals (control group). Pre-AML cases were distinct from controls and had more mutations per sample, higher variant allele frequencies, indicating greater clonal expansion, and showed enrichment of mutations in specific genes. Genetic parameters were used to derive a model that accurately predicted AML-free survival; this model was validated in an independent cohort of 29 pre-AML cases and 262 controls. Because AML is rare, we also developed an AML predictive model using a large electronic health record database that identified individuals at greater risk. Collectively our findings provide proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation. This could in future enable earlier detection and monitoring, and may help to inform intervention. |
| Databáze: | OpenAIRE |
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