Since 2000, we have investigated 67 consecutive patients with stage I/II follicular lymphoma (FL) for the presence of BCL2/IGH rearrangements by polymerase chain reaction (PCR), real time quantitative PCR (RQ-PCR) and digital droplet PCR (ddPCR).
Arguably the MYC activity gain is the most constantly observed phenomenon (>70% of cases) in transformed FL/MALT/CLL (Richter's transformation) and co-occurs with specific aberrations such as the loss of p53, CDKN2A/B, or gain of BCL2/BCL6.
This paper describes how we discovered the juxtaposition of the MYC gene to the human immunoglobulin loci and how that finding was extended to characterize molecularly the t(14;18) chromosome translocation of follicular lymphoma and to clone the BCL2 gene.
These include B-lymphocyte proliferation and sustained clonal expansion by HCV-envelope protein stimulation of B-cell receptors, and prolonged HCV-infected B-cell growth by overexpression of an anti-apoptotic BCL-2 oncogene caused by the increased frequency of t(14;18) chromosomal translocations in follicular lymphomas.
Early data from the tazemetostat trials indicate an acceptable safety profile and early signs of activity in diffuse large B-cell lymphoma and follicular lymphoma, including patients with EZH2 wild-type and mutant tumors.
Follicular lymphoma (FL) is the most frequent indolent lymphoma in the Western world and is characterized in almost all cases by the t(14;18) translocation that results in overexpression of BCL2, an anti-apoptotic protein.
We analyzed the presence of the t(14;18)(q32;q21) as a surrogate marker of the malignant clone in cells of the FL microenvironment using combined fluorescence immunophenotyping and interphase cytogenetics targeting the BCL2 gene locus.
These results suggest a diverse portfolio of genetic alterations that may induce or regulate BCL2 expression or promote pathogenesis of t(14;18)-negative FL as well as a less specific but increased crosstalk with the microenvironment that may compensate for the lack of N-glycosylation.
The development of follicular lymphoma (FL) from a founder B cell with an upregulation of B-cell lymphoma 2 (BCL2), via the t(14;18) translocation, to a proliferating clone, poised to undergo further transformation to an aggressive lymphoma, illustrates the opportunistic Darwinian process of tumorigenesis.
FISH analysis confirmed the presence of IgH/BCL2 rearrangement in both the low grade follicular lymphoma (FL) and transformed Langerhans cells sarcoma (LCS) samples, demonstrating a clonal relationship.
The most common scenario is transformation of follicular lymphoma to either diffuse large B-cell lymphoma or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 translocations; however, other indolent subtypes such as marginal zone lymphoma, lymphoplasmacytic lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, or even nodular lymphocyte predominant Hodgkin lymphoma, can undergo similar histologic transformation.