t(14;18)(q32;q21) in chronic lymphocytic leukemia patients: Report of two cases and a literature review

Abstract

The chromosomal abnormality t(14;18)(q32;q21) is most commonly associated with germinal center-derived B-cell lymphomas, particularly follicular lymphoma (FL). Generally, it is considered a hallmark of FL. The t(14;18)(q32;q21) translocation is rare in chronic lymphocytic leukemia (CLL) and its prognostic significance remains unclear. In the present study, two cases of CLL with t(14;18)(q32;q21) were diagnosed using conventional cytogenetic analysis and fluorescence in situ hybridization. Both patients presented with leukemia and the morphological features and immunophenotypes were typical of CLL. Case 2 underwent a further lymph node biopsy, which established a diagnosis of CD5– CLL/small lymphocyte lymphoma. In addition to t(14;18)(q32;q21), trisomy 12 was identified in the same clone in Case 2. Both cases exhibited immunoglobulin heavy chain variable mutations, and heavy-chain variable region gene (VH) 4–39 and VH3-62 were used in Case 1 and Case 2, respectively. In addition, direct Sanger sequencing of exons 4–9 revealed that Case 2 harbored the tumor protein p53 mutation, c.829T>G. Both cases had indications for therapy. Case 1 responded well to chlorambucil treatment, and was still alive at the last follow-up. Conversely, Case 2 exhibited aggressive disease that appeared refractory to treatment, and eventually succumbed to the disease.

An unusual case of chronic lymphocytic leukemia with trisomy 12 and t(14;18) and a favorable response to ibrutinib

“…While t(14;18)(q32;q21) is a characteristic of follicular lymphoma, it is reported in around 20% of germinal center-derived B-cell lymphomas [8] . It has also been described in few case of CLL, with, however unclear prognostic significance [ 8 , 9 ]. The majority of CLL patients reported with t(14;18)(q32;q21) are men with a sex ratio of 2.5:1 and a median age at diagnosis of 51 years, suggesting a relatively younger occurrence compared to the average age of CLL diagnosis of around 70 years.…”

“…Among fourteen CLL patients with t(14;18)(q32;q21) reported to date, 7 had an additional trisomy 12 associated with atypical cellular morphological features including irregular nuclear contours and/or plasmacytoid differentiation as well as an atypical immunophenotype including negative CD5 expression, absence or weak CD23 expression, positive FMC-7, moderate to bright immunoglobulin light chain expression and bright CD20 expression. Furthermore, of the 10 patients tested for IGHV , 9 exhibited mutations ( Table 1 ) [8] [9] .…”

Chromosomal aberrations after induced pluripotent stem cells reprogramming

“…Furthermore, the presence of additional material on chromosome 14 was observed in one of our samples. Changes in 14q32, such as translocations and additional material, are observed in patients with lymphomas and lymphocytic leukemias ( Chen et al, 2016 ; Veloza et al, 2019 ).…”

Composite Lymphoma as Co-occurrence of Advanced Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Carrying Trisomy 12 and t(14;18) and Peripheral T-cell Lymphoma

“…11 Regarding the prognosis of B-CLL patients with t(14;18)(q32;q21) as a sole chromosomal abnormality, 2 of 4 such patients exhibited an unfavorable clinical course. 12,13 The present patient acquired t(14;18)(q32;q21) and trisomy 12 at the stage of CLL/PLL; therefore, collectively, t(14;18) (q32;q21) may be associated with a poor prognosis, although the accumulation of B-CLL cases with t(14;18)(q32;q21) is required. Regarding the relationship between the emergence of chromosomal abnormalities and disease progression, Cuneo et al noted an increase in the trisomy 12-carrying cell number as the clinical stage advanced, including in CLL/ PLL.…”