Chronic Lymphocytic Leukemia and Other Lymphoproliferative Disorders

2016 ◽  
Vol 32 (1) ◽  
pp. 175-189 ◽  
Author(s):  
Sarah Wall ◽  
Jennifer A. Woyach
Blood ◽  
1990 ◽  
Vol 76 (2) ◽  
pp. 393-400 ◽  
Author(s):  
R Foa ◽  
M Massaia ◽  
S Cardona ◽  
AG Tos ◽  
A Bianchi ◽  
...  

Abstract Tumor necrosis factor-alpha (TNF) is a cytokine that displays a pleomorphic array of effects on different cell populations. Evidence is presented that TNF may be constitutively produced by B-cell chronic lymphocytic leukemia (B-CLL) and hairy cell leukemia (HCL) cells and that it may play a relevant role in these diseases. These conclusions are based on the presence of circulating levels of TNF in the serum of 20 of the 24 patients tested (83.3%), while undetectable values were found in normal sera. The suggestion that the increased serum levels were due to the leukemic cell population is strengthened by the evidence that purified B-CLL and HCL cells may constitutively release variable degrees of TNF. These levels markedly increase after incubation with interferon gamma or phytohemagglutinin (PHA) plus phorbol myristate acetate (PMA). The cellular release of TNF by primary B-CLL cells was significantly (P less than .001) higher in B-CLL stage O-I patients compared with stage II-III patients. The demonstration that, in B-cell chronic lymphoproliferative disorders, the pathologic cells may release TNF was further confirmed by the presence of the mRNA for this cytokine in primary and/or in pre-activated cells. Recombinant TNF was capable of inducing a proliferative signal only in a minority of cases (4/24); in most cases it was ineffective, and, in a few, it reduced the degree of proliferation. Furthermore, in costimulatory experiments with interleukin-2 and PHA plus PMA, TNF was ineffective. On the other hand, when primary B-CLL cells were incubated in the presence of an anti-TNF antibody, in 8 of 12 independent experiments a 2- to 15-fold increase in thymidine uptake was documented. Taken together, these results suggest that TNF may play a regulatory role in the progression of the neoplastic clone in B-cell chronic lymphoproliferative disorders and may be implicated in some of the side effects associated with these diseases.


2010 ◽  
Vol 34 (9) ◽  
pp. 1235-1238 ◽  
Author(s):  
Dragan Jevremovic ◽  
Roxana S. Dronca ◽  
William G. Morice ◽  
Ellen D. McPhail ◽  
Paul J. Kurtin ◽  
...  

1989 ◽  
Vol 169 (1) ◽  
pp. 255-268 ◽  
Author(s):  
Z M Sthoeger ◽  
M Wakai ◽  
D B Tse ◽  
V P Vinciguerra ◽  
S L Allen ◽  
...  

CD5-expressing B lymphocytes from patients with selected chronic lymphoproliferative disorders were used to determine whether monoclonal populations of CD5+ human B cells produce autoantibodies. CD5+ B cells from 19 patients with chronic lymphocytic leukemia (CLL) and one with diffuse well-differentiated lymphocytic lymphoma (DWDL) were cultured, with and without mitogenic stimulation, to obtain Ig from these cells. 17 of the 20 samples produced Ig in vitro. mAb from nine of the 17 patients were reactive with either IgG, ssDNA, or dsDNA. In every instance, the autoantibodies displayed monotypic L chain usage that correlated precisely with the L chain expressed on the CD5+ leukemic B cell surface. These monoclonal autoantibodies varied in their degree of antigenic specificity; some were quite specific, reacting with only one antigen, whereas others were polyspecific, reacting with two or all three autoantigens tested. Three features distinguish these autoantibodies from those observed in prior studies of CD5+ B cells. First, they are clearly the products of monoclonal populations of CD5+ cells; second, several react with dsDNA, a specificity not previously reported and often seen in association with significant autoimmune disorders; and third, two of the monoclonal autoantibodies secreted by the CD5+ clones were of the IgG class. Although not all of the Ig-producing, CD5-expressing clones elaborated mAbs reactive with the autoantigens tested, greater than 50% did. It is possible that with a broader autoantigenic panel or with larger quantities of CLL/DWDL-derived Ig, even more autoantibody-producing clones might be identified. These studies may have important implications for the antigenic specificity of subsets of human B lymphocytes as well as for lymphoproliferative and autoimmune disorders in general.


Blood ◽  
1979 ◽  
Vol 53 (4) ◽  
pp. 545-551 ◽  
Author(s):  
BR Kaden ◽  
WF Rosse ◽  
TW Hauch

We have studied the thrombocytopenia of lymphoproliferative disorders using a measurement of membrane-bound IgG by an antiglobulin consumption assay. Nine patients with chronic lymphocytic leukemia (CLL) and thrombocytopenia had increased membrane-bound IgG. Two patients with non-Hodgkins lymphoma and 1 patient with Hodgkins disease also had thrombocytopenia and increased membrane-bound IgG. Five of the patients with CLL had positive direct antiglobulin (Coombs) tests on red cells; of these, 3 patients had hemolytic anemia. In eight of the 9 patients with CLL, thrombocytopenia, and increased platelet-bound-IgG, the platelet count increased with the administration of prednisone or an alkylating agent, with splenectomy, or with a combination of these.


Blood ◽  
1968 ◽  
Vol 31 (4) ◽  
pp. 480-489 ◽  
Author(s):  
LUNG T. YAM ◽  
W. J. MITUS

Abstract Lymphocyte β-glucuronidase activity was estimated semi-quantitatively by a cytochemical method. Strong enzyme activity was found to be present in the lymphocytes. In patients with chronic lymphocytic leukemia, lymphosarcoma and some cases of reticulum cell sarcoma, the lymphocyte β-glucuronidase activity was low. This was due to the presence of a large number of lymphocytes with low β-glucuronidase activity. The low β-glucuronidase content in the lymphocytes is usually associated with decreased ability of these cells to undergo transformation upon phytohemagglutinin stimulation; however, this association is not an absolute one.


Blood ◽  
1979 ◽  
Vol 53 (4) ◽  
pp. 545-551 ◽  
Author(s):  
BR Kaden ◽  
WF Rosse ◽  
TW Hauch

Abstract We have studied the thrombocytopenia of lymphoproliferative disorders using a measurement of membrane-bound IgG by an antiglobulin consumption assay. Nine patients with chronic lymphocytic leukemia (CLL) and thrombocytopenia had increased membrane-bound IgG. Two patients with non-Hodgkins lymphoma and 1 patient with Hodgkins disease also had thrombocytopenia and increased membrane-bound IgG. Five of the patients with CLL had positive direct antiglobulin (Coombs) tests on red cells; of these, 3 patients had hemolytic anemia. In eight of the 9 patients with CLL, thrombocytopenia, and increased platelet-bound-IgG, the platelet count increased with the administration of prednisone or an alkylating agent, with splenectomy, or with a combination of these.


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