Download Leukaemia Section t(2;19)(p12;q13) IGK/BCL3, t(14;19)(q32;q13) IGH/BCL3, t(19;22)(q13;q11) BCL3/IGL Atlas of Genetics and Cytogenetics

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t(2;19)(p12;q13) IGK/BCL3, t(14;19)(q32;q13)
IGH/BCL3, t(19;22)(q13;q11) BCL3/IGL
Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
(JLH)
Published in Atlas Database: June 2008
Online updated version : http://AtlasGeneticsOncology.org/Anomalies/t1419ID2050.html
DOI: 10.4267/2042/44499
This article is an update of :
Meeus P, Michaux L. t(14;19)(q32;q13). Atlas Genet Cytogenet Oncol Haematol 2001;5(4):283-284
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2009 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
Clinics and pathology
Note: The t(14;19)(q32.3;q13.2) -as well as the
variants t(2;19) and t(19;22)- is a recurrent
translocation found in patients with chronic B-cell
lymphoproliferative disorders.
This abnormality is cytogenetically identical but
molecularly distinct from the t(14;19)(q32;q13) with
IGH and CEBPA (or CEBPG) involvements, seen in
acute B-cell lymphoblastic leukaemia.
Disease
Chronic lymphocytic leukemia/small lymphocytic
lymphoma (B-CLL/SLL); most are the atypical form
(at times reported as variant CLL, or transformed
CLL), because of an atypical morphology and
phenotype (Michaux et al., 1996; Michaux et al., 1997),
but also for the presence of lymphocytosis (Soma et al.,
2006), the frequency of
t(14;19)(q32;q13) G-banding - Courtesy Jean-Luc Lai (top) and Diane H Norback, Eric B Johnson, and Sara Morrison-Delap, UW
Cytogenetic Services (middle and bottom).
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(6)
441
t(2;19)(p12;q13) IGK/BCL3, t(14;19)(q32;q13) IGH/BCL3, t(19;22)(q13;q11) BCL3/IGL
lymphadenopathy (Huh et al., 2007), young age
(median 50-60 years), male predominence (about
2M/1F), and an aggressive course of the disease
(Michaux et al., 1997).
Other diseases: marginal zone lymphoma (MZL),
splenic marginal zone lymphoma (SMZL), diffuse
large B-cell lymphoma (DLBCL), mantle cell
lymphoma, low grade B-cell non Hodgkin lymphoma
(NHL) not otherwise specified, aggressive B-cell NHL,
and even one case of biphenotypic (B/M) acute
leukemia.
A recent study reascertained and split the entity into the
following subgroups herein below described; the
accuracy of this proposal remains to be confirmed by
further studies, inasmuch as there is a real problem of
classification of t(14;19)(q32;q13) in chronic B-cell
lymphoproliferative disorders, as has been pointed out
(Soma et al., 2006; Huh et al., 2007):
"7q rearrangements cluster": 15% of cases: diagnosis of
MZL/SMZL or aggressive B-cell NHL mostly.
Medium complexity of the karyotype. IgVH mutated.
Aggressive diseases. Median age 65 (49-85).
"Deletion 17p cluster": 10% of cases: diagnosis of CLL
frequent. Complex karyotypes. IgVH mutated. Median
age 54.
"1q rearrangements, deletions 6q and 13q cluster": 30%
of cases: diagnosis of DLBCL or MZL and MZL in
transformation, less often, CLL. Complex karyotypes.
IgVH mutated. Aggressive diseases. Median age 65
(27-92).
"Trisomy 12 cluster": 45% of cases: diagnosis of CLL
in most cases, low complexity of the karyotype, IgVH
mutation rate low. This is the only cluster with an
unequal sex ratio: 14M/4F; median age 65 (35-95).
Huret JL
Cytogenetics
Cytogenetics morphological
The t(14;19)(q32.3;q13.2) is reciprocal and results in
14q+ and a 19q- derivative chromosomes.
Cytogenetics molecular
FISH is useful for identifying variant translocations.
Additional anomalies
t(14;19) is rarely the sole cytogenetic aberration.
Trisomy 12 is the most frequent associated
abnormality, and is observed in 50% of cases. del(6q),
del(7q), del(13q), del(17p) and additional 14q32
rearrangements can be found. Other chromosomes
involved in structural aberrations are 1q, 3p, 3q, 6p, 7q,
11q, 12p.
Variants
t(2;19)(p12;q13) IGK/BCL3 and t(19;22)(q13;q11)
BCL3/IGL, variants of the t(14;19)(q32;q13)
IGH/BCL3, have been described; they are found in the
same proportions as for the variants of the
t(8;14)(q24;q32).
COMPLEX TRANSLOCATIONS: Three way
"variants" are relatively frequent, compared to variants
in other recurrent translocations. t(14;17;19) and
t(7;19;14) were described.
Genes involved and proteins
IgH
Chronic B-cell lymphoproliferation.
Location
14q32
Note
IgK or IgL can replace IgH (see above).
Epidemiology
BCL3
103 published cases (40 reviewed in Soma et al., 2006;
7 cases in Huh et al., 2007; and 56 cases in MartinSubero et al., 2007). Annual incidence 30/106. The
t(14;19) occurs in less than 0.2 % of B-cell
malignancies.
Location
19q13
DNA/RNA
9 exons, spanning 11.5 kb. BCL3 mRNA is expressed
in a variety of tissues, particularly in spleen, liver and
lung.
Protein
Encodes a protein which contains seven ankyrin
repeats. Similar repeats are described in the structural
protein ankyrin, as well as in proteins involved in cell
cycle control and lineage determination (SW14, SW16,
lin2).
BCL3 is a member of the IkappaB family, whose
proteins regulate the NFkappaB family of transcription
factors. NFkappaB plays a major role in B-cell
development.
Phenotype/cell stem origin
Clinics
Often a slow evolutive disease.
Prognosis
Highly variable according to the staging: from staging
A: where the survival is not reduced compared to age
matched population, to staging C: with a median
survival of 2 yrs. t(14;19) is often associated with
rapidly progressive disease, and overall prognosis is
poor compared to the expected survival in chronic
lymphocytic leukemia and low-grade B-cell lymphoma.
The prognosis has to be reascertained according to new
(or further) sub-classification of the disease.
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(6)
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t(2;19)(p12;q13) IGK/BCL3, t(14;19)(q32;q13) IGH/BCL3, t(19;22)(q13;q11) BCL3/IGL
Huret JL
lymphoproliferative disorders. Genes Chromosomes Cancer.
1996 Jan;15(1):38-47
Result of the chromosomal
anomaly
Michaux L, Dierlamm J, Wlodarska I, Bours V, Van den Berghe
H, Hagemeijer A. t(14;19)/BCL3 rearrangements in
lymphoproliferative disorders: a review of 23 cases. Cancer
Genet Cytogenet. 1997 Mar;94(1):36-43
Hybrid gene
Description
The breakpoint is located in the 5' untranslated region
of the BCL3 gene. BCL3 is juxtaposed to the
immunoglobulin heavy chain gene locus on
chromosome 14 (often in the switch alpha region) in a
"head-to-head" configuration.
Soma LA, Gollin SM, Remstein ED, Ketterling RP, Flynn HC,
Rajasenan KK, Swerdlow SH. Splenic small B-cell lymphoma
with
IGH/BCL3
translocation.
Hum
Pathol.
2006
Feb;37(2):218-30
Huh YO, Abruzzo LV, Rassidakis GZ, Parry-Jones N, Schlette
E, Brito-Bapabulle V, Matutes E, Wotherspoon A, Keating MJ,
Medeiros LJ, Catovsky D. The t(14;19)(q32;q13)-positive small
B-cell leukaemia: a clinicopathologic and cytogenetic study of
seven cases. Br J Haematol. 2007 Jan;136(2):220-8
Fusion protein
Oncogenesis
No fusion protein. The translocation does not interrupt
the transcriptional integrity of BCL3, but is associated
with increased production of a BCL3 RNA of normal
size. The immunoglobulin enhancer is not present on
the same derivative chromosome as BCL3, suggesting
other mechanisms for overexpression.
The genes affected by overexpression of BCL3 remain
to be identified.
Martín-Subero JI, Ibbotson R, Klapper W, Michaux L, CalletBauchu E, Berger F, Calasanz MJ, De Wolf-Peeters C, Dyer
MJ, Felman P, Gardiner A, Gascoyne RD, Gesk S, Harder L,
Horsman DE, Kneba M, Küppers R, Majid A, Parry-Jones N,
Ritgen M, Salido M, Solé F, Thiel G, Wacker HH, Oscier D,
Wlodarska I, Siebert R. A comprehensive genetic and
histopathologic analysis identifies two subgroups of B-cell
malignancies carrying a t(14;19)(q32;q13) or variant BCL3translocation. Leukemia. 2007 Jul;21(7):1532-44
This article should be referenced as such:
References
Huret JL. t(2;19)(p12;q13) IGK/BCL3, t(14;19)(q32;q13)
IGH/BCL3, t(19;22)(q13;q11) BCL3/IGL. Atlas Genet
Cytogenet Oncol Haematol. 2009; 13(6):441-443.
Michaux L, Mecucci C, Stul M, Wlodarska I, Hernandez JM,
Meeus P, Michaux JL, Scheiff JM, Noël H, Louwagie A, Criel
A, Boogaerts M, Van Orshoven A, Cassiman JJ, Van Den
Berghe H. BCL3 rearrangement and t(14;19)(q32;q13) in
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443