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Blood, 23 April 2009, Vol. 113, No. 17, pp. 4011-4015. Prepublished online as a Blood First Edition Paper on January 14, 2009; DOI 10.1182/blood-2008-10-183483.
LYMPHOID NEOPLASIA The MLL recombinome of adult CD10-negative B-cell precursor acute lymphoblastic leukemia: results from the GMALL study group1 Charité Universitätsmedizin Berlin, Campus Benjamin Franklin (CBF), Medizinische Klinik III, Berlin; 2 Institut für Pharmazeutische Biologie/ZAFES/Diagnostikzentrum für Akute Leukämie (DCAL), Goethe-Universität, Frankfurt/Main; 3 Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ), Braunschweig; 4 Medizinische Klinik II, Universitätsklinikum Schleswig-Holstein (UKSH), Campus Kiel, Kiel; 5 Max Planck-Institut (MPI) für Molekulare Genetik, Berlin; and 6 Goethe-Universität, Medizinische Klinik II, Frankfurt, Germany 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 [ClinicalTrials.gov] and NCT00198991 [ClinicalTrials.gov] .
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