Portada Simposios - Supplements - Haematologica

240 Haematologica (ed. esp.), volumen 85, supl. 2, octubre 2000
Table 1. Incidence of mutations of the bcl-6 5’ non-coding region in normal B cells and B cell lymphomas
Type of cell
References
Normal cell Mutated cells (%)
PBL cells IgM+/IgD+ 0 Science 1998
Tonsil MC IgM+/IgD+ 5.7; 4 PNAS 1998; Blood 1999
Spleen MC IgD+ 0 Mateo 2000
PBL cells IgA, IgG 30-42 Science 1998
Tonsil GC B cells 32; 54 PNAS 1998; Blood 1999
Spleen GC B cells IgD- 30 Mateo 2000
Spleen MZ cells IgM+/IgD– 35 Mateo 2000
B cell lymphomas Mutated cases (%)
MCL 5; 4.8; 10 PNAS 1998; Blood 1999; Blood 2000
CLL 15; 30; 36;42 PNAS 1998; Blood 2000; Leukemia 2000;
Blood 2000
SMZL 13 Mateo 2000
SLL 22 Blood 2000
HCL 25 Blood 2000
BL 37 Blood 2000
LPL 40 Blood 2000
MZL-MALT 42; 33 Blood 1999; Blood 2000
FL 37; 42; 60 PNAS 1998; Blood 1999; Blood 2000
DLBCL 59 PNAS 1998
Primary splenic DLBCL 60 Blood 2000
PBL: peripheral blood lymphocytes; MC: mantle cells; GC: germinal centre; MZ: marginal zone; MCL: mantle cell lymphoma; CLL: chronic lymphocytic
leukaemia; SMZL: splenic marginal zone lymphoma; SLL: small lymphocytic lymphoma; HCL: hairy cell leukaemia; BL: Burkitt lymphoma; LPL:
lymphoplasmocytoid lymphoma; MZL-MALT: marginal zone lymphoma – mucosa-associated lymphoid tissue; DLBCL: diffuse large B cell lymphoma.
1.6
1.0
BCL-6
IgV H
25
20
BCL-6 (×10 -2 /bp)
0.8
0.6
0.4
15
10
IgV H
(×10 -2 /bp)
0.2
5
MCL
5%
CLL
15%
FL
37%
BL
37%
(PNAS 1998)
DLBCL
59%
MM
33%
Figure 1. Frequency of BCL6
and IGV H mutations
in lymphomas.
Table 2. Somatic hypermutation of IGV H and BCL-6
Occurs in germinal center B-cells, benign and malignant
Occurs at 2 kb from the transcription start point
Single substitutions over deletions
Transitions over transversions
Mutations occur in “hot spot” (RGYW) (A/G G C/T T/A)
The frequency of mutations in BCL-6 is 10 to 100 times
lower than in IGV H
variable region (IgV H ) gene, which increases their affinity
with the antigens present in the germinal centre
microenvironment.
Although it was initially assumed that the process
of somatic hypermutation in normal B lymphocytes
was restricted to Ig loci, including heavy and light
chain variable region genes, analogous mutations in
the bcl-6 gene were further described, showing promoter-dependent
hypermutations in the non-coding