The KMT2A recombinome of acute leukemias in 2023.


Journal

Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895

Informations de publication

Date de publication:
05 2023
Historique:
received: 08 02 2023
accepted: 15 03 2023
revised: 09 03 2023
medline: 11 5 2023
pubmed: 6 4 2023
entrez: 5 4 2023
Statut: ppublish

Résumé

Chromosomal rearrangements of the human KMT2A/MLL gene are associated with de novo as well as therapy-induced infant, pediatric, and adult acute leukemias. Here, we present the data obtained from 3401 acute leukemia patients that have been analyzed between 2003 and 2022. Genomic breakpoints within the KMT2A gene and the involved translocation partner genes (TPGs) and KMT2A-partial tandem duplications (PTDs) were determined. Including the published data from the literature, a total of 107 in-frame KMT2A gene fusions have been identified so far. Further 16 rearrangements were out-of-frame fusions, 18 patients had no partner gene fused to 5'-KMT2A, two patients had a 5'-KMT2A deletion, and one ETV6::RUNX1 patient had an KMT2A insertion at the breakpoint. The seven most frequent TPGs and PTDs account for more than 90% of all recombinations of the KMT2A, 37 occur recurrently and 63 were identified so far only once. This study provides a comprehensive analysis of the KMT2A recombinome in acute leukemia patients. Besides the scientific gain of information, genomic breakpoint sequences of these patients were used to monitor minimal residual disease (MRD). Thus, this work may be directly translated from the bench to the bedside of patients and meet the clinical needs to improve patient survival.

Identifiants

pubmed: 37019990
doi: 10.1038/s41375-023-01877-1
pii: 10.1038/s41375-023-01877-1
pmc: PMC10169636
doi:

Substances chimiques

KMT2A protein, human 0
Histone-Lysine N-Methyltransferase EC 2.1.1.43
Myeloid-Lymphoid Leukemia Protein 149025-06-9

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

988-1005

Informations de copyright

© 2023. The Author(s).

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Auteurs

C Meyer (C)

DCAL/Institute of Pharm. Biology, Goethe-University, Frankfurt/Main, Germany.

P Larghero (P)

DCAL/Institute of Pharm. Biology, Goethe-University, Frankfurt/Main, Germany.

B Almeida Lopes (B)

DCAL/Institute of Pharm. Biology, Goethe-University, Frankfurt/Main, Germany.
Instituto Nacional de Câncer (INCA), Rio de Janeiro, RJ, Brazil.

T Burmeister (T)

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Dept. of Hematology, Oncology and Tumor Immunology, Berlin, Germany.

D Gröger (D)

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Dept. of Hematology, Oncology and Tumor Immunology, Berlin, Germany.

R Sutton (R)

Molecular Diagnostics, Children's Cancer Institute, Lowy Cancer Research Centre, UNSW, Sydney, NSW, Australia.

N C Venn (NC)

Molecular Diagnostics, Children's Cancer Institute, Lowy Cancer Research Centre, UNSW, Sydney, NSW, Australia.

G Cazzaniga (G)

Tettamanti Research Center, Pediatrics, University of Milano-Bicocca/Fondazione Tettamanti, Monza, Italy.

L Corral Abascal (L)

Tettamanti Research Center, Pediatrics, University of Milano-Bicocca/Fondazione Tettamanti, Monza, Italy.

G Tsaur (G)

Regional Children's Hospital, Ekaterinburg, Russian Federation; Research Institute of Medical Cell Technologies, Ekaterinburg, Russian Federation.

L Fechina (L)

Regional Children's Hospital, Ekaterinburg, Russian Federation; Research Institute of Medical Cell Technologies, Ekaterinburg, Russian Federation.

M Emerenciano (M)

Instituto Nacional de Câncer (INCA), Rio de Janeiro, RJ, Brazil.

M S Pombo-de-Oliveira (MS)

Instituto Nacional de Câncer (INCA), Rio de Janeiro, RJ, Brazil.

T Lund-Aho (T)

Laboratory of Clinical Genetics, Fimlab Laboratories, Tampere, Finland.

T Lundán (T)

Department of Clinical Chemistry and Laboratory Division, University of Turku and Turku University Hospital, Turku, Finland.

M Montonen (M)

Department of Clinical Chemistry and Laboratory Division, University of Turku and Turku University Hospital, Turku, Finland.

V Juvonen (V)

Department of Clinical Chemistry and Laboratory Division, University of Turku and Turku University Hospital, Turku, Finland.

J Zuna (J)

CLIP, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.

J Trka (J)

CLIP, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.

P Ballerini (P)

Biological Hematology, AP-HP A. Trousseau, Pierre et Marie Curie University, Paris, France.

H Lapillonne (H)

Biological Hematology, AP-HP A. Trousseau, Pierre et Marie Curie University, Paris, France.

V H J Van der Velden (VHJ)

Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.

E Sonneveld (E)

Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands.

E Delabesse (E)

Institut Universitaire du Cancer de Toulouse, Toulouse Cedex 9, France.

R R C de Matos (RRC)

Cytogenetics Department, Bone Marrow Transplantation Unit, National Cancer Institute (INCA), Rio de Janeiro, Brazil.

M L M Silva (MLM)

Cytogenetics Department, Bone Marrow Transplantation Unit, National Cancer Institute (INCA), Rio de Janeiro, Brazil.

S Bomken (S)

Wolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.

K Katsibardi (K)

Division of Pediatric Hematology-Oncology, First Department of Pediatrics, National and Kapodistrian University of Athens, "Aghia Sophia" Children's Hospital, Athens, Greece.

M Keernik (M)

Genetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia.

N Grardel (N)

Department of Hematology, CHU Lille, France.

J Mason (J)

Northern Institute for Cancer Research, Newcastle University and the Great North Children's West Midlands Regional Genetics Laboratory, Birmingham Women's and Children's NHS Foundation Trust, Mindelsohn Way, Birmingham, United Kingdom.

R Price (R)

Northern Institute for Cancer Research, Newcastle University and the Great North Children's West Midlands Regional Genetics Laboratory, Birmingham Women's and Children's NHS Foundation Trust, Mindelsohn Way, Birmingham, United Kingdom.

J Kim (J)

DCAL/Institute of Pharm. Biology, Goethe-University, Frankfurt/Main, Germany.
Department of Laboratory Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea.

C Eckert (C)

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatric Oncology/Hematology, Berlin, Germany.

L Lo Nigro (L)

Centro di Riferimento Regionale di Ematologia ed Oncologia Pediatrica, Azienda Policlinico "G. Rodolico", Catania, Italy.

C Bueno (C)

Josep Carreras Leukemia Research Institute. Barcelona, Spanish Network for Advanced Therapies (RICORS-TERAV, ISCIII); Spanish Collaborative Cancer Network (CIBERONC. ISCIII); University of Barcelona, Barcelona, Spain.
Josep Carreras Leukemia Research Institute. Barcelona, Spanish Network for Advanced Therapies (RICORS-TERAV, ISCIII); Spanish Collaborative Cancer Network (CIBERONC. ISCIII); Department of Biomedicine. University of Barcelona; and Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.

P Menendez (P)

Centro di Riferimento Regionale di Ematologia ed Oncologia Pediatrica, Azienda Policlinico "G. Rodolico", Catania, Italy.

U Zur Stadt (U)

Pediatric Hematology and Oncology and CoALL Study Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

P Gameiro (P)

Instituto Português de Oncologia, Departament of Hematology, Lisbon, Portugal.

L Sedék (L)

Department of Pediatric Hematology and Oncology, Medical University of Silesia, Zabrze, Poland.

T Szczepański (T)

Department of Pediatric Hematology and Oncology, Medical University of Silesia, Zabrze, Poland.

A Bidet (A)

Laboratoire d'Hématologie Biologique, CHU Bordeaux, Bordeaux, France.

V Marcu (V)

Hematology Laboratory, Sheba Medical Center, Tel-Hashomer, Israel.

K Shichrur (K)

Molecular Oncology Laboratory, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.

S Izraeli (S)

Pediatric Hematology-Oncology, Schneider Children's Medical Center, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

H O Madsen (HO)

Department of Clinical Immunology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

B W Schäfer (BW)

Division of Oncology and Children's Research Centre, University Children's Hospital Zurich, Zurich, Switzerland.

S Kubetzko (S)

Division of Oncology and Children's Research Centre, University Children's Hospital Zurich, Zurich, Switzerland.

R Kim (R)

Hematology Laboratory, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
Université Paris Cité, INSERM/CNRS U944/UMR7212, Institut de recherche Saint-Louis, Paris, France.

E Clappier (E)

Hematology Laboratory, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
Université Paris Cité, INSERM/CNRS U944/UMR7212, Institut de recherche Saint-Louis, Paris, France.

H Trautmann (H)

Laboratory for Specialized Hematological Diagnostics, Medical Department II, University Hospital Schleswig-Holstein, Kiel, Germany.

M Brüggemann (M)

Laboratory for Specialized Hematological Diagnostics, Medical Department II, University Hospital Schleswig-Holstein, Kiel, Germany.

P Archer (P)

Bristol Genetics Laboratory, North Bristol NHS Trust, Bristol, United Kingdom.

J Hancock (J)

Bristol Genetics Laboratory, North Bristol NHS Trust, Bristol, United Kingdom.

J Alten (J)

Department of Pediatrics, University Hospital Schleswig-Holstein, Kiel, Germany.

A Möricke (A)

Department of Pediatrics, University Hospital Schleswig-Holstein, Kiel, Germany.

M Stanulla (M)

Department of Pediatrics, MHH, Hanover, Germany.

J Lentes (J)

Institute of Human Genetics, Medical School Hannover, Hannover, Germany.

A K Bergmann (AK)

Institute of Human Genetics, Medical School Hannover, Hannover, Germany.

S Strehl (S)

St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria.

S Köhrer (S)

St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria.
Labdia Labordiagnostik, Vienna, Austria.

K Nebral (K)

St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria.
Labdia Labordiagnostik, Vienna, Austria.

M N Dworzak (MN)

St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria.
Labdia Labordiagnostik, Vienna, Austria.
St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria.

O A Haas (OA)

St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria.
Labdia Labordiagnostik, Vienna, Austria.
St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria.

C Arfeuille (C)

Genetics Department, AP-HP, Hopital Robert Debré, Paris, France.

A Caye-Eude (A)

Genetics Department, AP-HP, Hopital Robert Debré, Paris, France.
Université Paris Cité, Inserm U1131, Institut de recherche Saint-Louis, Paris, France.

H Cavé (H)

Genetics Department, AP-HP, Hopital Robert Debré, Paris, France.
Université Paris Cité, Inserm U1131, Institut de recherche Saint-Louis, Paris, France.

R Marschalek (R)

DCAL/Institute of Pharm. Biology, Goethe-University, Frankfurt/Main, Germany. Rolf.Marschalek@em.uni-frankfurt.de.

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Classifications MeSH