Successful clinical trials of venetoclax/ABT-199, a specific inhibitor of BCL-2, have led to its approval for a refractory form of chronic lymphocytic leukaemia and to scores of on-going trials for other malignancies.
It was shown that bcl-2 gene rearrangements were exclusively confined to centroblastic-centrocytic lymphomas. bcl-1 rearrangements were found in two cases of chronic lymphocytic leukaemia.
The nine patients with 5'BCL2 rearrangement included two with follicular lymphoma, four with diffuse large cell lymphoma and immunoblastic variant, two with leukemic phase of follicular lymphoma, and one with CLL.
In humans, a single-nucleotide polymorphism in the B-cell chronic lymphocytic leukemia/lymphoma-2 (Bcl-2) gene, rs956572, has been found to significantly modulate Bcl-2 protein expression in the brain.
These findings are consistent with rs539846 influencing CLL susceptibility through differential RELA binding, with direct modulation of BMF expression impacting on anti-apoptotic BCL2, a hallmark of oncogenic dependency in CLL.
These tumors are genetically characterized by B-cell leukemia/lymphoma 2 (BCL2) translocation and mutation of genes involved in chromatin modification.
DNA was extracted from paired peripheral blood (PB) cells and plasma for polymerase chain reaction (PCR)-based detection of immunoglobulin heavy chain (IgH) and T-cell receptor gamma chain (TCR-gamma) rearrangements, and B-cell leukemia/lymphoma (BCL)-1/IgH and BCL-2/IgH translocations.
Taken together, our data do not support the use of the (-938C>A) BCL-2 polymorphism as a prognostic marker in CLL and argue against its postulated role in modulating Bcl-2 levels.
Tested parameters included, estimation of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and glucose levels, testicular samples for histopathology and estimation of malondialdehyde (MDA), total antioxidant capacity (TAC), and B-cell leukemia/lymphoma-2 (BCL-2) levels as well as sperm count and motility.
We have previously shown that transgenic (tg) mice expressing in B lymphocytes both BCL-2 and a TNFR-associated factor 2 (TRAF2) mutant lacking the really interesting new gene and zinc finger domains (TRAF2DN) develop small lymphocytic lymphoma and chronic lymphocytic leukemia with high incidence (Zapata et al.2004.Proc.Nat.Acad.Sci.USA 101: 16600-16605).
The expression of proteins related to apoptosis, cysteinyl aspartate-specific proteinase 12 (caspase-12) and B-cell leukemia 2 (Bcl-2), was measured by western blot.
Analysis of the expression profiles showed that the significantly up-regulated genes included cyclin D1, cell division cycle 37 (CDC37) and B-cell leukemia/lymphoma-2 (BCL-2), while the down-regulated genes included cyclin D2 and CD9 antigen (p24) in MM cases with cyclin D1 overexpression.
A number of new treatment options have recently emerged for chronic lymphocytic leukemia (CLL) patients, including the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, phosphatidylinositol-3-kinase (PI3K) delta isoform inhibitor idelalisib combined with rituximab, the Bcl-2 antagonist venetoclax, and the new anti-CD20 antibodies obinutuzumab and ofatumumab.
The P2X7 receptor gene polymorphism 1513 A-->C has no effect on clinical prognostic markers, in vitro sensitivity to fludarabine, Bcl-2 family protein expression or survival in B-cell chronic lymphocytic leukaemia.
Each protein was measured in a panel of leukemia/lymphoma cell lines and B-cells from chronic lymphocytic leukemia (CLL) patients treated with the BCL-2/BCL-X<sub>L</sub> inhibitor navitoclax.