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Optimized cytogenetic risk-group stratification of KMT2A-rearranged pediatric acute myeloid leukemia
RE. van Weelderen, CJ. Harrison, K. Klein, Y. Jiang, J. Abrahamsson, T. Alonzo, R. Aplenc, N. Arad-Cohen, E. Bart-Delabesse, B. Buldini, B. De Moerloose, MN. Dworzak, S. Elitzur, JM. Fernández Navarro, A. Gamis, RB. Gerbing, BF. Goemans, HA. de...
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
Grantová podpora
U10 CA180886
NCI NIH HHS - United States
U10 CA180899
NCI NIH HHS - United States
NLK
Directory of Open Access Journals
od 2016
PubMed Central
od 2016
Europe PubMed Central
od 2016
ROAD: Directory of Open Access Scholarly Resources
od 2016
- MeSH
- akutní myeloidní leukemie * genetika mortalita MeSH
- chromozomální aberace MeSH
- dítě MeSH
- genová přestavba MeSH
- histonlysin-N-methyltransferasa * genetika MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- prognóza MeSH
- protoonkogenní protein MLL * genetika MeSH
- retrospektivní studie MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
A comprehensive international consensus on the cytogenetic risk-group stratification of KMT2A-rearranged (KMT2A-r) pediatric acute myeloid leukemia (AML) is lacking. This retrospective (2005-2016) International Berlin-Frankfurt-Münster Study Group study on 1256 children with KMT2A-r AML aims to validate the prognostic value of established recurring KMT2A fusions and additional cytogenetic aberrations (ACAs) and to define additional, recurring KMT2A fusions and ACAs, evaluating their prognostic relevance. Compared with our previous study, 3 additional, recurring KMT2A-r groups were defined: Xq24/KMT2A::SEPT6, 1p32/KMT2A::EPS15, and 17q12/t(11;17)(q23;q12). Across 13 KMT2A-r groups, 5-year event-free survival probabilities varied significantly (21.8%-76.2%; P < .01). ACAs occurred in 46.8% of 1200 patients with complete karyotypes, correlating with inferior overall survival (56.8% vs 67.9%; P < .01). Multivariable analyses confirmed independent associations of 4q21/KMT2A::AFF1, 6q27/KMT2A::AFDN, 10p12/KMT2A::MLLT10, 10p11.2/KMT2A::ABI1, and 19p13.3/KMT2A::MLLT1 with adverse outcomes, but not those of 1q21/KMT2A::MLLT11 and trisomy 19 with favorable and adverse outcomes, respectively. Newly identified ACAs with independent adverse prognoses were monosomy 10, trisomies 1, 6, 16, and X, add(12p), and del(9q). Among patients with 9p22/KMT2A::MLLT3, the independent association of French-American-British-type M5 with favorable outcomes was confirmed, and those of trisomy 6 and measurable residual disease at end of induction with adverse outcomes were identified. We provide evidence to incorporate 5 adverse-risk KMT2A fusions into the cytogenetic risk-group stratification of KMT2A-r pediatric AML, to revise the favorable-risk classification of 1q21/KMT2A::MLLT11 to intermediate risk, and to refine the risk-stratification of 9p22/KMT2A::MLLT3 AML. Future studies should validate the associations between the newly identified ACAs and outcomes and unravel the underlying biological pathogenesis of KMT2A fusions and ACAs.
Children's Cancer Center National Center for Child Health and Development Tokyo Japan
DCOG Dutch Childhood Oncology Group Utrecht The Netherlands
Department of Clinical Sciences Pediatrics Umeå University Umeå Sweden
Department of Hematology and Oncology Children's Mercy Hospital Kansas City MO
Department of Oncology St Jude Children's Research Hospital Memphis TN
Department of Pediatric Hematology and Oncology Aghia Sophia Children's Hospital Athens Greece
Department of Pediatric Hematology and Oncology Hôpital Armand Trousseau Paris France
Department of Pediatric Hematology and Oncology University Hospital Essen Essen Germany
Department of Pediatric Oncohematology Hospital Universitari i Politècnic la Fe Valencia Spain
Department of Pediatrics and Adolescent Medicine Aarhus University Hospital Aarhus Denmark
Department of Pediatrics and Adolescent Medicine Hong Kong Children's Hospital Kowloon Bay Hong Kong
Department of Pediatrics Osaka University Graduate School of Medicine Suita Japan
Department of Statistics Children's Oncology Group Monrovia CA
Division of Biostatistics University of Southern California Los Angeles CA
Division of Oncology Children's Hospital of Philadelphia Philadelphia PA
Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
Citace poskytuje Crossref.org
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