t(2;19)(p12;q13.3) IGK/BCL3
t(14;19)(q32;q13.3) IGH/BCL3
t(19;22)(q13.3;q11) BCL3/IGL

2008-06-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers; CHU Poitiers Hospital, F-86021 Poitiers, France
2.Centrum voor Menselijke Erfelijkheid, UZ Gasthuisberg, Herestraat 49, 3000 Leuven, Belgie

Clinics and Pathology

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 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).

Phenotype stem cell origin

Chronic B-cell lymphoproliferation

Epidemiology

103 published cases (40 reviewed in Soma et al., 2006; 7 cases in Huh et al., 2007; and 56 cases in Martin-Subero et al., 2007). Annual incidence 30/106. The t(14;19) occurs in less than 0.2 % of B-cell malignancies.

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 the disease.

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).

Genes Involved and Proteins

Gene name
IGH (Immunoglobulin Heavy)
Location
14q32.33
Note
IgK or IgL can replace IgH (see above).
Gene name
BCL3 (B-cell CLL/lymphoma 3)
Location
19q13.32
Dna rna description
9 exons, spanning 11.5 kb. BCL3 mRNA is expressed in a variety of tissues, particularly in spleen, liver and lung.
Protein description
  • 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.
  • Result of the Chromosomal Anomaly

    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.

    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.
  • Highly cited references

    Pubmed IDYearTitleCitations
    333300842020Case Report: Chronic Lymphocytic Leukemia With a Rare Translocation t(14;19)(q32;q13) Involving IGH/BCL3 Rearrangements: Report of Three Chinese Cases and Literature Review.1
    305751082019IGH translocations in chronic lymphocytic leukemia: Clinicopathologic features and clinical outcomes.6
    235818352013Acquisition of t(11;14) in a patient with chronic lymphocytic leukemia carrying both t(14;19)(q32;q13.1) and +12.5
    267197662015Rare double-hit with two translocations involving IGH both, with BCL2 and BCL3, in a monoclonal B-cell lymphoma/leukemia.2
    215024232011Chronic lymphocytic leukemia with t(14;19)(q32;q13) is characterized by atypical morphologic and immunophenotypic features and distinctive genetic features.14
    189404742008BCL2 and BCL3 are recurrent translocation partners of the IGH locus.4
    164269232006Splenic small B-cell lymphoma with IGH/BCL3 translocation.4

    Bibliography

    Pubmed IDLast YearTitleAuthors
    171292292007The t(14;19)(q32;q13)-positive small B-cell leukaemia: a clinicopathologic and cytogenetic study of seven cases.Huh YO et al
    174959772007A comprehensive genetic and histopathologic analysis identifies two subgroups of B-cell malignancies carrying a t(14;19)(q32;q13) or variant BCL3-translocation.Martín-Subero JI et al
    90782891997t(14;19)/BCL3 rearrangements in lymphoproliferative disorders: a review of 23 cases.Michaux L et al
    88247241996BCL3 rearrangement and t(14;19)(q32;q13) in lymphoproliferative disorders.Michaux L et al
    164269232006Splenic small B-cell lymphoma with IGH/BCL3 translocation.Soma LA et al

    Summary

    Fusion gene

    IGK/BCL3 IGK (14q32.33) BCL3 (19q13.32) M t(2;19)(p11;q13)

    Note

    The t(14;19)(q32.3;q13.3) -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.
    Atlas Image
    t(14;19)(q32;q13) G-banding Left: - Courtesy Jean-Luc Lai (top) and Diane H Norback, Eric B Johnson, and Sara Morrison-Delap, http://www.slh.wisc.edu/cytogenetics (middle and bottom); right: top: ideograms, bottom middle two: G and R-bandings - Courtesy Peter Meus; R-banding (right) : Coutesy Chrystèle Bilhou-Nabera and Nasséra Abermil.

    Citation

    Jean-Loup Huret

    t(2;19)(p12;q13.3) IGK/BCL3
    t(14;19)(q32;q13.3) IGH/BCL3
    t(19;22)(q13.3;q11) BCL3/IGL

    Atlas Genet Cytogenet Oncol Haematol. 2008-06-01

    Online version: http://atlasgeneticsoncology.org/haematological/2050/t(2;19)(p12;q13-3)-igk-bcl3-br-t(14;19)(q32;q13-3)-igh-bcl3-br-t(19;22)(q13-3;q11)-bcl3-igl

    Historical Card

    2001-08-01 t(2;19)(p12;q13.3) IGK/BCL3
    t(14;19)(q32;q13.3) IGH/BCL3
    t(19;22)(q13.3;q11) BCL3/IGL
     by  Lucienne Michaux,Peter Meeus 

    Centrum voor Menselijke Erfelijkheid, UZ Gasthuisberg, Herestraat 49, 3000 Leuven, Belgie

    External Links