Spontaneous apoptosis and proliferation detected by BCL-2 and CD71 proteins are important progression indicators within ZAP-70 negative chronic lymphocytic leukemia.
ABSTRACT In chronic lymphocytic leukemia (CLL), inhibition of spontaneous apoptosis determines a worse prognosis and increasing evidences show that disease progression relies also upon cycling CLL cells. We investigated bcl-2, as measure of apoptosis, and CD71, as measure of proliferation, by flow cytometry in 265 patients with CLL. Combining bcl-2 with CD71 values, we defined three subgroups: (1) bcl2 - CD71-; (2) bcl2 + CD71+; and (3) bcl2 + CD71- or bcl2- CD71+. Both a shorter progression-free survival (PFS) and overall survival (OS) were observed in ZAP-70+ (p < 0.00001) and in patients with bcl2 + CD71+ (p < 0.00001 and p = 0.02). The patients with discordant in bcl2 + CD71- and bcl2- CD71+ showed an intermediate outcome. Noteworthy, patients with bcl2 + CD71+ showed a shorter PFS within ZAP-70 negative subgroup (p = 0.00009). In multivariate analysis of PFS, age (p = 0.005), beta-(2) microglobulin (B(2)-M) (p = 0.003), bcl-2 (p = 0.004), CD49d (p = 0.001), and ZAP-70 (p < 0.001) resulted to be significant prognostic factors. The independent prognostic significance of B(2)-M (p = 0.009) and bcl-2 (p = 0.03) was confirmed within ZAP-70 negative patients. Bcl-2 and CD71 can be considered as interesting progression indicators, which should be validated in an independent cohort of patients, to take timely therapeutic decisions in CLL.
- SourceAvailable from: pnas.org[show abstract] [hide abstract]
ABSTRACT: A cell surface glycoprotein antigen with an apparent molecular weight of about 100,000 that is selectively expressed on proliferating cells was purified from deoxycholate-solubilized membranes of a cultured human leukemic thymus-derived (T) cell line by affinity chromatography on a monoclonal antibody-Sepharose column. A conventional xenoantiserum prepared by immunization with the affinity-purified glycoprotein was found to contain antibodies against a serum component that bound tightly to cultured cells. This molecule was shown to be specifically associated with the cell surface glycoprotein purified by immunoprecipitation from lysates of cells. We have identified the serum component as transferrin and conclude that the membrane glycoprotein is the cell surface transferrin receptor.Proceedings of the National Academy of Sciences 06/1981; 78(5):3039-43. · 9.74 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: The monoclonal antibody OKT9 was applied to cryostat sections of 267 non-Hodgkin's lymphomas and related neoplasms. It was found that the transferrin receptor is expressed by a wide variety of B- and T-lineage non-Hodgkin's lymphomas. The OKT9 staining also was loosely correlated with the three morphologic grades of non-Hodgkin's lymphomas identified by the International Working Formulation. In general, higher grade lymphomas more often and more intensely expressed the T9 antigen. However, transferrin receptor expression by certain histologic subtypes of lymphoma did not correlate with their morphologic grade: low-grade follicular lymphomas expressed the T9 antigen more frequently than diffuse low-grade lymphomas; diffuse small cleaved cell lymphomas were stained by OKT9 less often than other histologic subtypes of intermediate-grade lymphomas; and diffuse immunoblastic lymphomas expressed transferrin receptors less often than the other high-grade histologic subtypes of non-Hodgkin's lymphoma. Intermediate lymphocytic lymphomas, not recognized in the International Working Formulation, were infrequently and weakly stained by OKT9 in a manner similar to diffuse low-grade lymphomas. We obtained clinical follow-up data on 43 individuals with chronic lymphocytic leukemia/small lymphocytic lymphoma and 64 individuals with diffuse large cell and immunoblastic lymphoma. Transferrin receptor expression in these two groups did not correlate significantly with survival.Cancer 06/1988; 61(9):1844-51. · 5.20 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: B-cell chronic lymphocytic leukemia (B-CLL) is considered an accumulative disease of antigen-naive CD5(+) B lymphocytes that circulate in the resting state. However, to evaluate the possibility that B-CLL cells resemble antigen-experienced and activated B cells, we analyzed the expression of markers of cellular activation and differentiation on CD5(+)CD19(+) cells from B-CLL patients and from age-matched healthy donors. The leukemic cells from all B-CLL patients, including those that lack significant numbers of V gene mutations, bear the phenotype of activated B cells based on the overexpression of the activation markers CD23, CD25, CD69, and CD71 and the underexpression of CD22, Fcgamma receptor IIb, CD79b, and immunoglobulin D that are down-regulated by cell triggering and activation. Furthermore, these leukemic cells resemble antigen-experienced lymphocytes in the underexpression of molecules that are down-regulated by cell triggering and in the uniform expression of CD27, an identifier of memory B cells. A comparison of the phenotypes of B-CLL patients with and without immunoglobulin V gene mutations suggests that the 2 subgroups differ both in specific marker expression (CD69, CD71, CD62 L, CD40, CD39, and HLA-DR) and in the time since antigenic stimulation, based on the reciprocal relationship of CD69 and CD71 expression. These findings imply that the leukemic cells from all B-CLL cases (irrespective of V gene mutations) exhibit features of activated and of antigen-experienced B lymphocytes and that the B-CLL cells that differ in immunoglobulin V genotype may have different antigen-encounter histories.Blood 07/2002; 99(11):4087-93. · 9.06 Impact Factor