Translocation t(1;6)(p35.3;p25.2): a new recurrent aberration in "unmutated" B-CLL.
Although reciprocal chromosomal translocations are not typical for B-cell chronic lymphocytic leukemia (B-CLL), we identified the novel t(1;6)(p35.3;p25.2) in eight patients with this disorder. Interestingly, all cases showed lack of somatically mutated IgV(H). Clinical, morphological, immunologic, and genetic features of these patients are described. Briefly, the age ranged from 33 to 81 years (median: 62.5 years) and the sex ratio was 6M:2F. Most of the patients (6/8) presented with advanced clinical stage. Therapy was required in seven cases. After a median follow-up of 28 months, five patients are alive and three died from disease evolution. Three cases developed transformation into diffuse large B-cell lymphoma. Translocation t(1;6) was found as the primary karyotypic abnormality in three patients. Additional chromosomal aberrations included changes frequently found in unmutated B-CLL, that is, del(11)(q), trisomy 12 and 17p aberrations. Fluorescence in situ hybridization analysis performed in seven cases allowed us to map the t(1;6) breakpoints to the 1p35.3 and 6p25.2 chromosomal bands, respectively. The latter breakpoint was located in the genomic region coding for MUM1/IRF4, one of the key regulators of lymphocyte development and proliferation, suggesting involvement of this gene in the t(1;6). Molecular characterization of the t(1;6)(p35.3;p25.2), exclusively found in unmutated subtype of B-CLL, is in progress.
Michaux
L
L
Center for Human Genetics, Catholic University of Leuven, Herestraat 49, 3000 Leuven, Belgium.
Wlodarska
I
I
Rack
K
K
Stul
M
M
Criel
A
A
Maerevoet
M
M
Marichal
S
S
Demuynck
H
H
Mineur
P
P
Kargar Samani
K
K
Van Hoof
A
A
Ferrant
A
A
Marynen
P
P
Hagemeijer
A
A
D002878:Chromosomes, Human, Pair 1; D002896:Chromosomes, Human, Pair 6; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D014178:Translocation, Genetic