B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes

Damle RN, Ghiotto F, Valetto A, Albasiano E, Fais F, Yan XJ, Sison CP, Allen SL, Kolitz J, Schulman P, Vinciguerra VP, et al. (2002)
BLOOD 99(11): 4087-4093.

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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. (C) 2002 by The American Society of Hematology.
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Damle RN, Ghiotto F, Valetto A, et al. B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes. BLOOD. 2002;99(11):4087-4093.
Damle, R. N., Ghiotto, F., Valetto, A., Albasiano, E., Fais, F., Yan, X. J., Sison, C. P., et al. (2002). B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes. BLOOD, 99(11), 4087-4093.
Damle, R. N., Ghiotto, F., Valetto, A., Albasiano, E., Fais, F., Yan, X. J., Sison, C. P., Allen, S. L., Kolitz, J., Schulman, P., et al. (2002). B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes. BLOOD 99, 4087-4093.
Damle, R.N., et al., 2002. B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes. BLOOD, 99(11), p 4087-4093.
R.N. Damle, et al., “B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes”, BLOOD, vol. 99, 2002, pp. 4087-4093.
Damle, R.N., Ghiotto, F., Valetto, A., Albasiano, E., Fais, F., Yan, X.J., Sison, C.P., Allen, S.L., Kolitz, J., Schulman, P., Vinciguerra, V.P., Budde, P., Frey, J., Rai, K.R., Ferrarini, M., Chiorazzi, N.: B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes. BLOOD. 99, 4087-4093 (2002).
Damle, RN, Ghiotto, F, Valetto, A, Albasiano, E, Fais, F, Yan, XJ, Sison, CP, Allen, SL, Kolitz, J, Schulman, P, Vinciguerra, VP, Budde, P, Frey, Jürgen, Rai, KR, Ferrarini, M, and Chiorazzi, N. “B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes”. BLOOD 99.11 (2002): 4087-4093.
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