The MLL recombinome of adult CD10-negative B-cell precursor acute lymphoblastic leukemia: results from the GMALL study group

Burmeister, T., Meyer, C., Schwartz, S., Hofmann, J., Molkentin, M., Kowarz, E., Schneider, B., Raff, Thorsten, Reinhardt, R., Gokbuget, N., Hoelzer, D., Thiel, E. and Marschalek, R. (2009) The MLL recombinome of adult CD10-negative B-cell precursor acute lymphoblastic leukemia: results from the GMALL study group Blood, 113 (17). pp. 4011-4015. DOI 10.1182/blood-2008-10-183483.

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Abstract

MLL translocations in adult B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) are largely restricted to the immature CD10(-) immunophenotypes. MLL-AF4 is known to be the most frequent fusion transcript, but the exact frequencies of MLL aberrations in CD10(-) adult BCP-ALL are unknown. We present a genetic characterization of 184 BCR-ABL(-)CD10(-) adult ALL cases (156 cyIg(-), 28 cyIg(+)) diagnosed between 2001 and 2007 at the central diagnostic laboratory of the GMALL study group. Patient samples were investigated by RT-PCR for MLL-AF4, MLL-ENL, and MLL-AF9 and by long-distance inverse polymerase chain reaction, thus also allowing the identification of unknown MLL fusion partners at the genomic level. MLL-AF4 was detected in 101 (54.9%) and MLL-ENL in 11 (6.0%) cases. In addition, rare MLL fusion genes were found: 2 MLL-TET1 cases, not previously reported in ALL, 1 MLL-AF9, 1 MLL-PTD, a novel MLL-ACTN4, and an MLL-11q23 fusion. Chromosomal breakpoints were determined in all 118 positive cases, revealing 2 major breakpoint cluster regions in the MLL gene. Characteristic features of MLL+ patients were significantly lower CD10 expression, expression of the NG2 antigen, a higher white blood count at diagnosis, and female sex. Proposals are made for diagnostic assessment. The clinical studies are registered at http://www.clinicaltrials.gov as NCT00199056 and NCT00198991. (Blood. 2009;113:4011-4015)

Document Type: Article
Keywords: minimal-residual-diseaseacute myeloid-leukemia german multicenter trials partner genes fusion aberrations t(10/11)(q22,q23) alpha-actinin-4 rearrangement transcripts
Research affiliation: OceanRep > The Future Ocean - Cluster of Excellence
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Refereed: Yes
DOI etc.: 10.1182/blood-2008-10-183483
ISSN: 0006-4971
Projects: Future Ocean
Date Deposited: 11 Feb 2011 12:14
Last Modified: 24 Oct 2017 12:28
URI: http://eprints.uni-kiel.de/id/eprint/9321

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