Optimized cytogenetic risk-group stratification of KMT2A-rearranged pediatric acute myeloid leukemia

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Optimized cytogenetic risk-group stratification of KMT2A-rearranged pediatric acute myeloid leukemia

van Weelderen, Romy E. (författare): Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; Emma Children's Hospital, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands

Harrison, Christine J. (författare): Leukemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle-upon-Tyne, United Kingdom

Klein, Kim (författare): Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; Emma Children's Hospital, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands; Department of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, Netherlands

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Jiang, Yilin (författare): Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands

Abrahamsson, Jonas (författare): Department of Pediatrics, Institute of Clinical Sciences, Salgrenska University Hospital, Gothenburg, Sweden

Alonzo, Todd (författare): Division of Biostatistics, University of Southern California, CA, Los Angeles, United States

Aplenc, Richard (författare): Division of Oncology, Children's Hospital of Philadelphia, PA, Philadelphia, United States

Arad-Cohen, Nira (författare): Department of Pediatric Hematology-Oncology, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel

Bart-Delabesse, Emmanuelle (författare): Institut Universitaire du Cancer Toulouse-Oncopole, Laboratoire d'Hématologie Secteur Génétique des Hémopathies, Toulouse, France

Buldini, Barbara (författare): Division of Pediatric Hematology, Oncology, and Stem Cell Transplant, Department of Maternal and Child Health, Padua University, Padua, Italy

De Moerloose, Barbara (författare): Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium

Dworzak, Michael N. (författare): Department of Pediatrics, St. Anna Children's Hospital, Medical University of Vienna, St. Anna Children's Cancer Research Institute, Vienna, Austria

Elitzur, Sarah (författare): Department of Pediatric Hematology and Oncology, Schneider Children's Medical Center, Tel Aviv University, Tel Aviv, Israel

Fernández Navarro, José M. (författare): Department of Pediatric Oncohematology, Hospital Universitari i Politècnic la Fe, Valencia, Spain

Gamis, Alan (författare): Department of Hematology and Oncology, Children's Mercy Hospital, MO, Kansas City, United States

Gerbing, Robert B. (författare): Department of Statistics, Children's Oncology Group, CA, Monrovia, United States

Goemans, Bianca F. (författare): Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands

de Groot-Kruseman, Hester A. (författare): Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; DCOG, Dutch Childhood Oncology Group, Utrecht, Netherlands

Guest, Erin (författare): Department of Hematology and Oncology, Children's Mercy Hospital, MO, Kansas City, United States

Ha, Shau-Yin (författare): Department of Pediatrics & Adolescent Medicine, Hong Kong Children's Hospital, Kowloon Bay, Hong Kong

Hasle, Henrik (författare): Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark

Kelaidi, Charikleia (författare): Department of Pediatric Hematology and Oncology, Aghia Sophia Children's Hospital, Athens, Greece

Lapillonne, Hélène (författare): Department of Pediatric Hematology and Oncology, Hôpital Armand Trousseau, Paris, France

Leverger, Guy (författare): Department of Pediatric Hematology and Oncology, Hôpital Armand Trousseau, Paris, France

Locatelli, Franco (författare): Department of Pediatric Hematology and Oncology and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesù, Catholic University of the Sacred Heart, Rome, Italy

Miyamura, Takako (författare): Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan

Norén-Nyström, Ulrika (författare): Umeå universitet,Pediatrik

Polychronopoulou, Sophia (författare): Department of Pediatric Hematology and Oncology, Aghia Sophia Children's Hospital, Athens, Greece

Rasche, Mareike (författare): Department of Pediatric Hematology and Oncology, University Hospital Essen, Essen, Germany

Rubnitz, Jeffrey E. (författare): Department of Oncology, St. Jude Children's Research Hospital, TN, Memphis, United States

Stary, Jan (författare): Department of Pediatric Hematology and Oncology, University Hospital Motol, Second Faculty of Medicine, Charles University, Prague, Czech Republic

Tierens, Anne (författare): Department of Pathobiology and Laboratory Medicine, University Health Network, Toronto General Hospital, ON, Toronto, Canada

Tomizawa, Daisuke (författare): Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan

Zwaan, C. Michel (författare): Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; Department of Pediatric Oncology, Erasmus Medical Center Sophia Children's Hospital, Rotterdam, Netherlands

Kaspers, Gertjan J.L. (författare): Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands; Emma Children's Hospital, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands

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American Society of Hematology, 2024
2024
Engelska.
Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 8:12, s. 3200-3213

Relaterad länk:: https://doi.org/10.1...; visa fler...; https://umu.diva-por... (primary) (Raw object); https://urn.kb.se/re...; https://doi.org/10.1...; visa färre...

Tidskriftsartikel (refereegranskat)

Abstract Ämnesord

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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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Pediatrik (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Pediatrics (hsv//eng)

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Hematologi

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Av lärosätet: Umeå universitet

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