The MLL recombinome of adult CD10-negative B-cell precursor acute lymphoblastic leukemia: results from the GMALL study group.
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.
Burmeister
Thomas
T
Charité Universitätsmedizin Berlin, Campus Benjamin Franklin (CBF), Medizinische Klinik III, Berlin, Germany. thomas.burmeister@charite.de
Meyer
Claus
C
Schwartz
Stefan
S
Hofmann
Julia
J
Molkentin
Mara
M
Kowarz
Eric
E
Schneider
Björn
B
Raff
Thorsten
T
Reinhardt
Richard
R
Gökbuget
Nicola
N
Hoelzer
Dieter
D
Thiel
Eckhard
E
Marschalek
Rolf
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002877:Chromosomes, Human / Q000235:genetics; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics / Q000378:metabolism*; D015260:Neprilysin / Q000378:metabolism; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D012955:Societies, Medical
C497422:KMT2A protein, human; D011993:Recombinant Fusion Proteins; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D015260:Neprilysin