Our results show a dissociation between SHM and CSR in CLL and suggest that, in this disease, AID would require additional help for carrying out the SHM process.
Using an ELISA technique (Quantikine Human Angiogenin Immunoassay; R&D Systems), we measured serum angiogenin levels in 77 previously untreated Binet stage A B-cell chronic lymphocytic leukemia (CLL) patients.
Abnormal Ang-2 expression was also associated with unmutated IgV(H) genes (p<0.0001) and increased bone marrow angiogenesis (p=0.028), suggesting a role of Ang-2 in disease-progression of early CLL patients.
CD2 and CD13 expression, however, were more frequent (30% of cases) in familial CLL (P = 0.0003 for CD2, P = 0.006 for CD13) than in sporadic CLL (2-6%).
In CD19+ B-CLL cells, the Bax/Bcl-2 ratio was lower than in the CD19+ normal counterpart (1.3 versus 3.51; P<.05), mainly due to a Bcl-2 over expression (17.65 versus 9.02; P<.001).
We conclude that bfl-1 may be an important regulator of B-CLL apoptosis, which could contribute to disease progression and resistance to chemotherapy, and as such represent a future potential therapeutic target.
CCL21-driven B-CLL cell migration through Matrigel or human umbilical vein endothelial cells (HUVEC) was blocked by anti-CCR7 antibodies, CCR7-siRNA transfection, or the ERK1/2 inhibitor U0126, as well as by anti-MMP-9 antibodies or tissue inhibitor of metalloproteinase 1 (TIMP-1).
Furthermore, the expression of CCR7, the receptor for both CCL21 and CCL19, correlated with clinical lymphadenopathy, and blocking of CCR7 inhibited CLL cell TEM.
Based on the expression pattern, we propose that CLL-B cells prolong their survival through increased interaction with survival factors such as IL-4, and through various mechanisms of evading the immune response, such as turning off the expression of CD1c and CD1d, reducing immunogenic response to interferon gamma, inactivating T cell in B-T interaction and increasing the expression of immunoglobulin receptors which neutralize antibody-dependent cell-mediated cytotoxicity.
Based on the expression pattern, we propose that CLL-B cells prolong their survival through increased interaction with survival factors such as IL-4, and through various mechanisms of evading the immune response, such as turning off the expression of CD1c and CD1d, reducing immunogenic response to interferon gamma, inactivating T cell in B-T interaction and increasing the expression of immunoglobulin receptors which neutralize antibody-dependent cell-mediated cytotoxicity.