Immunoglobulin gene translocations in chronic lymphocytic leukemia: A report of 35 patients and review of the literature

De Braekeleer,Marc; Tous,Corine; Guéganic,Nadia; Le Bris,Marie‑Josée; Basinko,Audrey; Morel,Frédéric; Douet‑Guilbert,Nathalie

doi:10.3892/mco.2016.793

Immunoglobulin gene translocations in chronic lymphocytic leukemia: A report of 35 patients and review of the literature

Authors:
- Marc De Braekeleer
- Corine Tous
- Nadia Guéganic
- Marie‑Josée Le Bris
- Audrey Basinko
- Frédéric Morel
- Nathalie Douet‑Guilbert
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Affiliations: Faculty of Medicine and Health Sciences, University of Brest, Brest, France, Department of Cytogenetics and Reproductive Biology, Morvan Hospital, Regional University Hospital Center of Brest (CHRU), Brest, France, National Institute of Health and Medical Research (INSERM U1078), Brest, France
Published online on: February 26, 2016 https://doi.org/10.3892/mco.2016.793
Pages: 682-694

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Abstract

Chronic lymphocytic leukemia (CLL) represents the most common hematological malignancy in Western countries, with a highly heterogeneous clinical course and prognosis. Translocations involving the immunoglobulin (IG) genes are regularly identified. From 2000 to 2014, we identified an IG gene translocation in 18 of the 396 patients investigated at diagnosis (4.6%) and in 17 of the 275 analyzed during follow‑up (6.2%). A total of 4 patients in whom the IG translocation was identified at follow‑up did not carry the translocation at diagnosis. The IG heavy locus (IGH) was involved in 27 translocations (77.1%), the IG κ locus (IGK) in 1 (2.9%) and the IG λ locus (IGL) in 7 (20.0%). The chromosome band partners of the IG translocations were 18q21 in 16 cases (45.7%), 11q13 and 19q13 in 4 cases each (11.4% each), 8q24 in 3 cases (8.6%), 7q21 in 2 cases (5.7%), whereas 6 other bands were involved once (2.9% each). At present, 35 partner chromosomal bands have been described, but the partner gene has solely been identified in 10 translocations. CLL associated with IG gene translocations is characterized by atypical cell morphology, including plasmacytoid characteristics, and the propensity of being enriched in prolymphocytes. The IG heavy chain variable region (IGHV) mutational status varies between translocations, those with unmutated IGHV presumably involving cells at an earlier stage of B‑cell lineage. All the partner genes thus far identified are involved in the control of cell proliferation and/or apoptosis. The translocated partner gene becomes transcriptionally deregulated as a consequence of its transposition into the IG locus. With the exception of t(14;18)(q32;q21) and its variants, prognosis appears to be poor for the other translocations. Therefore, searching for translocations involving not only IGH, but also IGL and IGK, by banding and molecular cytogenetics is required. Furthermore, it is important to identify the partner gene to ensure the patients receive the optimal treatment.

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