New insights to the MLL recombinome of acute leukemias

C. Meyer; E. Kowarz; J. Hofmann; A. Renneville; J. Zuna; J. Trka; R. Ben Abdelali; E. Macintyre; E. De Braekeleer; M. De Braekeleer; E. Delabesse; M. P. de Oliveira; H. Cavé; E. Clappier; J. J.M. van Dongen; B. V. Balgobind; M. M. van den Heuvel-Eibrink; H. B. Beverloo; R. Panzer-Grümayer; A. Teigler-Schlegel; J. Harbott; E. Kjeldsen; S. Schnittger; U. Koehl; B. Gruhn; O. Heidenreich; L. C. Chan; S. F. Yip; M. Krzywinski; C. Eckert; A. Möricke; M. Schrappe; C. N. Alonso; B. W. Schäfer; J. Krauter; D. A. Lee; U. zur Stadt; G. Te Kronnie; R. Sutton; S. Izraeli; L. Trakhtenbrot; L. Lo Nigro; G. Tsaur; L. Fechina; T. Szczepanski; S. Strehl; D. Ilencikova; M. Molkentin; T. Burmeister; T. Dingermann; T. Klingebiel; R. Marschalek

doi:10.1038/leu.2009.33

New insights to the MLL recombinome of acute leukemias

C. Meyer, E. Kowarz, J. Hofmann, A. Renneville, J. Zuna, J. Trka, R. Ben Abdelali, E. Macintyre, E. De Braekeleer, M. De Braekeleer, E. Delabesse, M. P. de Oliveira, H. Cavé, E. Clappier, J. J.M. van Dongen, B. V. Balgobind, M. M. van den Heuvel-Eibrink, H. B. Beverloo, R. Panzer-Grümayer, A. Teigler-SchlegelJ. Harbott, E. Kjeldsen, S. Schnittger, U. Koehl, B. Gruhn, O. Heidenreich, L. C. Chan, S. F. Yip, M. Krzywinski, C. Eckert, A. Möricke, M. Schrappe, C. N. Alonso, B. W. Schäfer, J. Krauter, D. A. Lee, U. zur Stadt, G. Te Kronnie, R. Sutton, S. Izraeli, L. Trakhtenbrot, L. Lo Nigro, G. Tsaur, L. Fechina, T. Szczepanski, S. Strehl, D. Ilencikova, M. Molkentin, T. Burmeister, T. Dingermann, T. Klingebiel, R. Marschalek

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Chromosomal rearrangements of the human MLL gene are associated with high-risk pediatric, adult and therapy-associated acute leukemias. These patients need to be identified, treated appropriately and minimal residual disease was monitored by quantitative PCR techniques. Genomic DNA was isolated from individual acute leukemia patients to identify and characterize chromosomal rearrangements involving the human MLL gene. A total of 760 MLL-rearranged biopsy samples obtained from 384 pediatric and 376 adult leukemia patients were characterized at the molecular level. The distribution of MLL breakpoints for clinical subtypes (acute lymphoblastic leukemia, acute myeloid leukemia, pediatric and adult) and fused translocation partner genes (TPGs) will be presented, including novel MLL fusion genes. Combined data of our study and recently published data revealed 104 different MLL rearrangements of which 64 TPGs are now characterized on the molecular level. Nine TPGs seem to be predominantly involved in genetic recombinations of MLL: AFF1/AF4, MLLT3/ AF9, MLLT1/ENL, MLLT10/AF10, MLLT4/AF6, ELL, EPS15/AF1P, MLLT6/AF17 and SEPT6, respectively. Moreover, we describe for the first time the genetic network of reciprocal MLL gene fusions deriving from complex rearrangements.

Originele taal-2	Engels
Pagina's (van-tot)	1490-1499
Aantal pagina's	10
Tijdschrift	Leukemia
Volume	23
Nummer van het tijdschrift	8
DOI's	https://doi.org/10.1038/leu.2009.33
Status	Gepubliceerd - 2009
Extern gepubliceerd	Ja

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10.1038/leu.2009.33

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Meyer, C., Kowarz, E., Hofmann, J., Renneville, A., Zuna, J., Trka, J., Ben Abdelali, R., Macintyre, E., De Braekeleer, E., De Braekeleer, M., Delabesse, E., de Oliveira, M. P., Cavé, H., Clappier, E., van Dongen, J. J. M., Balgobind, B. V., van den Heuvel-Eibrink, M. M., Beverloo, H. B., Panzer-Grümayer, R., ... Marschalek, R. (2009). New insights to the MLL recombinome of acute leukemias. Leukemia, 23(8), 1490-1499. https://doi.org/10.1038/leu.2009.33

@article{99bfcad961c842ccb7b51bda50272278,

title = "New insights to the MLL recombinome of acute leukemias",

abstract = "Chromosomal rearrangements of the human MLL gene are associated with high-risk pediatric, adult and therapy-associated acute leukemias. These patients need to be identified, treated appropriately and minimal residual disease was monitored by quantitative PCR techniques. Genomic DNA was isolated from individual acute leukemia patients to identify and characterize chromosomal rearrangements involving the human MLL gene. A total of 760 MLL-rearranged biopsy samples obtained from 384 pediatric and 376 adult leukemia patients were characterized at the molecular level. The distribution of MLL breakpoints for clinical subtypes (acute lymphoblastic leukemia, acute myeloid leukemia, pediatric and adult) and fused translocation partner genes (TPGs) will be presented, including novel MLL fusion genes. Combined data of our study and recently published data revealed 104 different MLL rearrangements of which 64 TPGs are now characterized on the molecular level. Nine TPGs seem to be predominantly involved in genetic recombinations of MLL: AFF1/AF4, MLLT3/ AF9, MLLT1/ENL, MLLT10/AF10, MLLT4/AF6, ELL, EPS15/AF1P, MLLT6/AF17 and SEPT6, respectively. Moreover, we describe for the first time the genetic network of reciprocal MLL gene fusions deriving from complex rearrangements.",

author = "C. Meyer and E. Kowarz and J. Hofmann and A. Renneville and J. Zuna and J. Trka and {Ben Abdelali}, R. and E. Macintyre and {De Braekeleer}, E. and {De Braekeleer}, M. and E. Delabesse and {de Oliveira}, {M. P.} and H. Cav{\'e} and E. Clappier and {van Dongen}, {J. J.M.} and Balgobind, {B. V.} and {van den Heuvel-Eibrink}, {M. M.} and Beverloo, {H. B.} and R. Panzer-Gr{\"u}mayer and A. Teigler-Schlegel and J. Harbott and E. Kjeldsen and S. Schnittger and U. Koehl and B. Gruhn and O. Heidenreich and Chan, {L. C.} and Yip, {S. F.} and M. Krzywinski and C. Eckert and A. M{\"o}ricke and M. Schrappe and Alonso, {C. N.} and Sch{\"a}fer, {B. W.} and J. Krauter and Lee, {D. A.} and {zur Stadt}, U. and {Te Kronnie}, G. and R. Sutton and S. Izraeli and L. Trakhtenbrot and {Lo Nigro}, L. and G. Tsaur and L. Fechina and T. Szczepanski and S. Strehl and D. Ilencikova and M. Molkentin and T. Burmeister and T. Dingermann and T. Klingebiel and R. Marschalek",

note = "Funding Information: This work was made possible by and conducted within the framework of the International BFM Study Group. This study was supported by grant 107819 from the Deutsche Krebshilfe to RM, TD and TK; supported by grant R06/22 from the German Jos{\'e} Carreras Leukemia foundation to TB and supported by grant 2 P054 095 30 from the Polish Ministry of Science and Higher Education to TS.",

year = "2009",

doi = "10.1038/leu.2009.33",

language = "English",

volume = "23",

pages = "1490--1499",

journal = "Leukemia",

issn = "0887-6924",

publisher = "Springer Nature",

number = "8",

}

Meyer, C, Kowarz, E, Hofmann, J, Renneville, A, Zuna, J, Trka, J, Ben Abdelali, R, Macintyre, E, De Braekeleer, E, De Braekeleer, M, Delabesse, E, de Oliveira, MP, Cavé, H, Clappier, E, van Dongen, JJM, Balgobind, BV, van den Heuvel-Eibrink, MM, Beverloo, HB, Panzer-Grümayer, R, Teigler-Schlegel, A, Harbott, J, Kjeldsen, E, Schnittger, S, Koehl, U, Gruhn, B, Heidenreich, O, Chan, LC, Yip, SF, Krzywinski, M, Eckert, C, Möricke, A, Schrappe, M, Alonso, CN, Schäfer, BW, Krauter, J, Lee, DA, zur Stadt, U, Te Kronnie, G, Sutton, R, Izraeli, S, Trakhtenbrot, L, Lo Nigro, L, Tsaur, G, Fechina, L, Szczepanski, T, Strehl, S, Ilencikova, D, Molkentin, M, Burmeister, T, Dingermann, T, Klingebiel, T & Marschalek, R 2009, 'New insights to the MLL recombinome of acute leukemias', Leukemia, vol. 23, nr. 8, blz. 1490-1499. https://doi.org/10.1038/leu.2009.33

TY - JOUR

T1 - New insights to the MLL recombinome of acute leukemias

AU - Meyer, C.

AU - Kowarz, E.

AU - Hofmann, J.

AU - Renneville, A.

AU - Zuna, J.

AU - Trka, J.

AU - Ben Abdelali, R.

AU - Macintyre, E.

AU - De Braekeleer, E.

AU - De Braekeleer, M.

AU - Delabesse, E.

AU - de Oliveira, M. P.

AU - Cavé, H.

AU - Clappier, E.

AU - van Dongen, J. J.M.

AU - Balgobind, B. V.

AU - van den Heuvel-Eibrink, M. M.

AU - Beverloo, H. B.

AU - Panzer-Grümayer, R.

AU - Teigler-Schlegel, A.

AU - Harbott, J.

AU - Kjeldsen, E.

AU - Schnittger, S.

AU - Koehl, U.

AU - Gruhn, B.

AU - Heidenreich, O.

AU - Chan, L. C.

AU - Yip, S. F.

AU - Krzywinski, M.

AU - Eckert, C.

AU - Möricke, A.

AU - Schrappe, M.

AU - Alonso, C. N.

AU - Schäfer, B. W.

AU - Krauter, J.

AU - Lee, D. A.

AU - zur Stadt, U.

AU - Te Kronnie, G.

AU - Sutton, R.

AU - Izraeli, S.

AU - Trakhtenbrot, L.

AU - Lo Nigro, L.

AU - Tsaur, G.

AU - Fechina, L.

AU - Szczepanski, T.

AU - Strehl, S.

AU - Ilencikova, D.

AU - Molkentin, M.

AU - Burmeister, T.

AU - Dingermann, T.

AU - Klingebiel, T.

AU - Marschalek, R.

N1 - Funding Information: This work was made possible by and conducted within the framework of the International BFM Study Group. This study was supported by grant 107819 from the Deutsche Krebshilfe to RM, TD and TK; supported by grant R06/22 from the German José Carreras Leukemia foundation to TB and supported by grant 2 P054 095 30 from the Polish Ministry of Science and Higher Education to TS.

PY - 2009

Y1 - 2009

N2 - Chromosomal rearrangements of the human MLL gene are associated with high-risk pediatric, adult and therapy-associated acute leukemias. These patients need to be identified, treated appropriately and minimal residual disease was monitored by quantitative PCR techniques. Genomic DNA was isolated from individual acute leukemia patients to identify and characterize chromosomal rearrangements involving the human MLL gene. A total of 760 MLL-rearranged biopsy samples obtained from 384 pediatric and 376 adult leukemia patients were characterized at the molecular level. The distribution of MLL breakpoints for clinical subtypes (acute lymphoblastic leukemia, acute myeloid leukemia, pediatric and adult) and fused translocation partner genes (TPGs) will be presented, including novel MLL fusion genes. Combined data of our study and recently published data revealed 104 different MLL rearrangements of which 64 TPGs are now characterized on the molecular level. Nine TPGs seem to be predominantly involved in genetic recombinations of MLL: AFF1/AF4, MLLT3/ AF9, MLLT1/ENL, MLLT10/AF10, MLLT4/AF6, ELL, EPS15/AF1P, MLLT6/AF17 and SEPT6, respectively. Moreover, we describe for the first time the genetic network of reciprocal MLL gene fusions deriving from complex rearrangements.

AB - Chromosomal rearrangements of the human MLL gene are associated with high-risk pediatric, adult and therapy-associated acute leukemias. These patients need to be identified, treated appropriately and minimal residual disease was monitored by quantitative PCR techniques. Genomic DNA was isolated from individual acute leukemia patients to identify and characterize chromosomal rearrangements involving the human MLL gene. A total of 760 MLL-rearranged biopsy samples obtained from 384 pediatric and 376 adult leukemia patients were characterized at the molecular level. The distribution of MLL breakpoints for clinical subtypes (acute lymphoblastic leukemia, acute myeloid leukemia, pediatric and adult) and fused translocation partner genes (TPGs) will be presented, including novel MLL fusion genes. Combined data of our study and recently published data revealed 104 different MLL rearrangements of which 64 TPGs are now characterized on the molecular level. Nine TPGs seem to be predominantly involved in genetic recombinations of MLL: AFF1/AF4, MLLT3/ AF9, MLLT1/ENL, MLLT10/AF10, MLLT4/AF6, ELL, EPS15/AF1P, MLLT6/AF17 and SEPT6, respectively. Moreover, we describe for the first time the genetic network of reciprocal MLL gene fusions deriving from complex rearrangements.

UR - http://www.scopus.com/inward/record.url?scp=68749120703&partnerID=8YFLogxK

U2 - 10.1038/leu.2009.33

DO - 10.1038/leu.2009.33

M3 - Article

C2 - 19262598

AN - SCOPUS:68749120703

SN - 0887-6924

VL - 23

SP - 1490

EP - 1499

JO - Leukemia

JF - Leukemia

IS - 8

ER -

New insights to the MLL recombinome of acute leukemias

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