This phase II study will look at the response rate of patients with relapsed or refractory Burkitt Lymphoma/Leukemia and high-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6
following treatment with CPI-613.
Those lymphoma cells expressed diffuse positive immunohistochemical stain for CD20, CD79a, CD5, and cyclin D1, but were negative for CD10, CD23, BCL6
, and MUM1.
A hallmark of these neoplasms is translocations that do not result in mRNA fusions but instead juxtapose strong enhancer elements to proto-oncogenes, such as BCL2, BCL6
, CCND1, and MYC, leading to their overexpression.
proto-oncogene suppresses p53 expression in germinal-centre B cells.
Apart from GCB and ABC DLBCL subtypes, diagnosis of double-hit lymphoma (DHL) is based on the presence of MYC rearrangements in addition to BCL2 and/or BCL6
Immunohistochemical analysis revealed that [beta]-cells expressed monotypic surface IgM, CD19, CD20, CD79a, CD10, and BCL6
, with Ki-67 proliferative fraction >95%, which were diagnostic for BL.
Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6
by chromatin-modifying drugs in human cancer cells.
Based on the immunoreactivity for CD10, BCL6
, MUM-1, immunohistochemical analysis confirmed the diagnosis of DLBCL, NOS, centroblastic variant, and NGC.
Caption: Figure 5: Immunohistochemical studies showed the malignant cells positive for CD20 (a), CD10, and BCL6
. They are negative for CD3 (b) and MUM-1 (c), and Ki-67 (proliferative index) is 95% (d).
Jenkins, "Opposing signals from the Bcl6
transcription factor and the interleukin-2 receptor generate T helper 1 central and effector memory cells," Immunity, vol.
Some of the potential targets of miR-302b-3p identified in humans (TargetScanHuman 7.1) are MAP3K2, BCL6
, CCND2, CCND1, FGF10, RADA2, SMAD2, PAK3, and TGFfiR2 .
The tumours are composed of a monomorphic population of rapidly proliferating medium-sized B-cells characterized by the expression of IgM, CD10, and BCL6
and bearing functionally rearranged and somatically mutated Ig sequences indicative of a germinal centroblast origin .