The KMT2A recombinome of acute leukemias in 2023

C. Meyer; P. Larghero; B. Almeida Lopes; T. Burmeister; D. Gröger; R. Sutton; N. C. Venn; G. Cazzaniga; L. Corral Abascal; G. Tsaur; L. Fechina; M. Emerenciano; M. S. Pombo-de-Oliveira; T. Lund-Aho; T. Lundán; M. Montonen; V. Juvonen; J. Zuna; J. Trka; P. Ballerini; H. Lapillonne; V. H.J. Van der Velden; E. Sonneveld; E. Delabesse; R. R.C. de Matos; M. L.M. Silva; S. Bomken; K. Katsibardi; M. Keernik; N. Grardel; J. Mason; R. Price; J. Kim; C. Eckert; L. Lo Nigro; C. Bueno; P. Menendez; U. zur Stadt; P. Gameiro; L. Sedék; T. Szczepański; A. Bidet; V. Marcu; K. Shichrur; S. Izraeli; H. O. Madsen; B. W. Schäfer; S. Kubetzko; R. Kim; E. Clappier; H. Trautmann; M. Brüggemann; P. Archer; J. Hancock; J. Alten; A. Möricke; M. Stanulla; J. Lentes; A. K. Bergmann; S. Strehl; S. Köhrer; K. Nebral; M. N. Dworzak; O. A. Haas; C. Arfeuille; A. Caye-Eude; H. Cavé; R. Marschalek

doi:10.1038/s41375-023-01877-1

The KMT2A recombinome of acute leukemias in 2023

C. Meyer, P. Larghero, B. Almeida Lopes, T. Burmeister, D. Gröger, R. Sutton, N. C. Venn, G. Cazzaniga, L. Corral Abascal, G. Tsaur, L. Fechina, M. Emerenciano, M. S. Pombo-de-Oliveira, T. Lund-Aho, T. Lundán, M. Montonen, V. Juvonen, J. Zuna, J. Trka, P. BalleriniH. Lapillonne, V. H.J. Van der Velden, E. Sonneveld, E. Delabesse, R. R.C. de Matos, M. L.M. Silva, S. Bomken, K. Katsibardi, M. Keernik, N. Grardel, J. Mason, R. Price, J. Kim, C. Eckert, L. Lo Nigro, C. Bueno, P. Menendez, U. zur Stadt, P. Gameiro, L. Sedék, T. Szczepański, A. Bidet, V. Marcu, K. Shichrur, S. Izraeli, H. O. Madsen, B. W. Schäfer, S. Kubetzko, R. Kim, E. Clappier, H. Trautmann, M. Brüggemann, P. Archer, J. Hancock, J. Alten, A. Möricke, M. Stanulla, J. Lentes, A. K. Bergmann, S. Strehl, S. Köhrer, K. Nebral, M. N. Dworzak, O. A. Haas, C. Arfeuille, A. Caye-Eude, H. Cavé, R. Marschalek^*

^*Corresponding author for this work

Immunology

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Abstract

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.

Original language	English
Pages (from-to)	988-1005
Number of pages	18
Journal	Leukemia
Volume	37
Issue number	5
DOIs	https://doi.org/10.1038/s41375-023-01877-1
Publication status	Published - May 2023

Bibliographical note

FUNDING:
Open Access funding enabled and organized by Projekt DEAL.

Publisher Copyright:
© 2023, The Author(s).

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The KMT2A recombinome of acute leukemias in 2023Final published version, 3.74 MBLicence: CC BY

Cite this

Meyer, C., Larghero, P., Almeida Lopes, B., Burmeister, T., Gröger, D., Sutton, R., Venn, N. C., Cazzaniga, G., Corral Abascal, L., Tsaur, G., Fechina, L., Emerenciano, M., Pombo-de-Oliveira, M. S., Lund-Aho, T., Lundán, T., Montonen, M., Juvonen, V., Zuna, J., Trka, J., ... Marschalek, R. (2023). The KMT2A recombinome of acute leukemias in 2023. Leukemia, 37(5), 988-1005. https://doi.org/10.1038/s41375-023-01877-1

@article{9d608b2fcf164899bd8fe785dd94e77b,

title = "The KMT2A recombinome of acute leukemias in 2023",

abstract = "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{\textquoteright}-KMT2A, two patients had a 5{\textquoteright}-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.",

author = "C. Meyer and P. Larghero and {Almeida Lopes}, B. and T. Burmeister and D. Gr{\"o}ger and R. Sutton and Venn, {N. C.} and G. Cazzaniga and {Corral Abascal}, L. and G. Tsaur and L. Fechina and M. Emerenciano and Pombo-de-Oliveira, {M. S.} and T. Lund-Aho and T. Lund{\'a}n and M. Montonen and V. Juvonen and J. Zuna and J. Trka and P. Ballerini and H. Lapillonne and {Van der Velden}, {V. H.J.} and E. Sonneveld and E. Delabesse and {de Matos}, {R. R.C.} and Silva, {M. L.M.} and S. Bomken and K. Katsibardi and M. Keernik and N. Grardel and J. Mason and R. Price and J. Kim and C. Eckert and {Lo Nigro}, L. and C. Bueno and P. Menendez and {zur Stadt}, U. and P. Gameiro and L. Sed{\'e}k and T. Szczepa{\'n}ski and A. Bidet and V. Marcu and K. Shichrur and S. Izraeli and Madsen, {H. O.} and Sch{\"a}fer, {B. W.} and S. Kubetzko and R. Kim and E. Clappier and H. Trautmann and M. Br{\"u}ggemann and P. Archer and J. Hancock and J. Alten and A. M{\"o}ricke and M. Stanulla and J. Lentes and Bergmann, {A. K.} and S. Strehl and S. K{\"o}hrer and K. Nebral and Dworzak, {M. N.} and Haas, {O. A.} and C. Arfeuille and A. Caye-Eude and H. Cav{\'e} and R. Marschalek",

note = "FUNDING: Open Access funding enabled and organized by Projekt DEAL. Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = may,

doi = "10.1038/s41375-023-01877-1",

language = "English",

volume = "37",

pages = "988--1005",

journal = "Leukemia",

issn = "0887-6924",

publisher = "Springer Nature",

number = "5",

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Meyer, C, Larghero, P, Almeida Lopes, B, Burmeister, T, Gröger, D, Sutton, R, Venn, NC, Cazzaniga, G, Corral Abascal, L, Tsaur, G, Fechina, L, Emerenciano, M, Pombo-de-Oliveira, MS, Lund-Aho, T, Lundán, T, Montonen, M, Juvonen, V, Zuna, J, Trka, J, Ballerini, P, Lapillonne, H, Van der Velden, VHJ, Sonneveld, E, Delabesse, E, de Matos, RRC, Silva, MLM, Bomken, S, Katsibardi, K, Keernik, M, Grardel, N, Mason, J, Price, R, Kim, J, Eckert, C, Lo Nigro, L, Bueno, C, Menendez, P, zur Stadt, U, Gameiro, P, Sedék, L, Szczepański, T, Bidet, A, Marcu, V, Shichrur, K, Izraeli, S, Madsen, HO, Schäfer, BW, Kubetzko, S, Kim, R, Clappier, E, Trautmann, H, Brüggemann, M, Archer, P, Hancock, J, Alten, J, Möricke, A, Stanulla, M, Lentes, J, Bergmann, AK, Strehl, S, Köhrer, S, Nebral, K, Dworzak, MN, Haas, OA, Arfeuille, C, Caye-Eude, A, Cavé, H & Marschalek, R 2023, 'The KMT2A recombinome of acute leukemias in 2023', Leukemia, vol. 37, no. 5, pp. 988-1005. https://doi.org/10.1038/s41375-023-01877-1

TY - JOUR

T1 - The KMT2A recombinome of acute leukemias in 2023

AU - Meyer, C.

AU - Larghero, P.

AU - Almeida Lopes, B.

AU - Burmeister, T.

AU - Gröger, D.

AU - Sutton, R.

AU - Venn, N. C.

AU - Cazzaniga, G.

AU - Corral Abascal, L.

AU - Tsaur, G.

AU - Fechina, L.

AU - Emerenciano, M.

AU - Pombo-de-Oliveira, M. S.

AU - Lund-Aho, T.

AU - Lundán, T.

AU - Montonen, M.

AU - Juvonen, V.

AU - Zuna, J.

AU - Trka, J.

AU - Ballerini, P.

AU - Lapillonne, H.

AU - Van der Velden, V. H.J.

AU - Sonneveld, E.

AU - Delabesse, E.

AU - de Matos, R. R.C.

AU - Silva, M. L.M.

AU - Bomken, S.

AU - Katsibardi, K.

AU - Keernik, M.

AU - Grardel, N.

AU - Mason, J.

AU - Price, R.

AU - Kim, J.

AU - Eckert, C.

AU - Lo Nigro, L.

AU - Bueno, C.

AU - Menendez, P.

AU - zur Stadt, U.

AU - Gameiro, P.

AU - Sedék, L.

AU - Szczepański, T.

AU - Bidet, A.

AU - Marcu, V.

AU - Shichrur, K.

AU - Izraeli, S.

AU - Madsen, H. O.

AU - Schäfer, B. W.

AU - Kubetzko, S.

AU - Kim, R.

AU - Clappier, E.

AU - Trautmann, H.

AU - Brüggemann, M.

AU - Archer, P.

AU - Hancock, J.

AU - Alten, J.

AU - Möricke, A.

AU - Stanulla, M.

AU - Lentes, J.

AU - Bergmann, A. K.

AU - Strehl, S.

AU - Köhrer, S.

AU - Nebral, K.

AU - Dworzak, M. N.

AU - Haas, O. A.

AU - Arfeuille, C.

AU - Caye-Eude, A.

AU - Cavé, H.

AU - Marschalek, R.

PY - 2023/5

Y1 - 2023/5

N2 - 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.

AB - 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.

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U2 - 10.1038/s41375-023-01877-1

DO - 10.1038/s41375-023-01877-1

M3 - Article

C2 - 37019990

AN - SCOPUS:85151568484

SN - 0887-6924

VL - 37

SP - 988

EP - 1005

JO - Leukemia

JF - Leukemia

IS - 5

ER -

The KMT2A recombinome of acute leukemias in 2023

Abstract

Bibliographical note

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