Chromosomal aberration of the 11q23 locus in acute leukemia and frequency of MLL gene translocation: results in 378 adult patients.
Structural abnormality of the 11q23 band (11q23+) bearing the MLL gene translocation (MLL+) is a recurrent chromosome change observed in 3% to 7% of acute lymphoblastic leukemias and in 3% to 4% of acute myeloblastic leukemias. The resolution of conventional cytogenetics (CC) in detecting 11q23 rearrangement is limited when the translocative partner has a telomeric location; furthermore, CC can barely discriminate between true 11q23+/MLL+ and rearrangements clustering within the 11q22 to approximately 25 region without MLL involvement (MLL-). We characterized a series of 378 consecutive patients with adult acute leukemia by using CC, fluorescence in situ hybridization (FISH), and multiplex karyotyping (M-FISH) analysis. Our aim was to define the frequency of cryptic MLL+ cases and the frequency of MLL+ within 11q22 to approximately 25+ cases. As expected, FISH was more sensitive than CC in detecting MLL+ cases, but rather unexpectedly, 9 (45%) of 20 patients with 11q22 to approximately 25+ were MLL-. A better characterization of 11q22 to approximately 25+/MLL- leukemias is relevant for the identification of new, recurrent translocations. Moreover, these cases should be readily distinguishable from 11q23+/MLL+ cases. We recommend that karyotypic analysis always be complemented by molecular or FISH methods to unravel MLL rearrangements.
Department of Hematology, S'Eugenio Hospital, University of Tor Vergata, Rome, Italy.
M Christina
MC
Cox
Paola
P
Panetta
Francesco
F
Lo-Coco
Giovanni
G
Del Poeta
Adriano
A
Venditti
Luca
L
Maurillo
M Ilaria
MI
Del Principe
Alessandro
A
Mauriello
Lucia
L
Anemona
Antonio
A
Bruno
Carla
C
Mazzone
Paolo
P
Palombo
Sergio
S
Amadori
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D003581:Cytodiagnosis / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D007938:Leukemia / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein; D011519:Proto-Oncogenes; D012680:Sensitivity and Specificity; D014157:Transcription Factors; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase