The clinical, immunological and diagnostic significance of the phenotype of circulating, malignant, B-lymphocyte clones

Stuart, Nicholas Simon Andrew (1990) The clinical, immunological and diagnostic significance of the phenotype of circulating, malignant, B-lymphocyte clones. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

Two hundred and twelve cases of chronic, B-cell leukaemia were investigated by direct and indirect antibody rosette methods to determine the expression of the following surface antigens: MHC class II, MRBCr, CD1, CD3, CDS, CDS, CD9, CD10, CDllb, CD1 Ic, CD19, CD20, CD21, CD22, CD23, CD24, CD25, CD37, CD38, CD39, CDw40 and surface heavy- and light-chain type. The patient group was, in the main, histolog-ically defined and comprised 174 cases of chronic lymphocytic leukaemia (CLL), 19 of hairy cell leukaemia (HCL) and 9 each of leukaemia associated with centroblastic-centrocytic (CB-CC) and centrocytic (CC) lym-phoma.

The diseases showed different but overlapping phenotypcs. These differences could be related, in part, to the point in normal B-cell development at which the malignancy arose. The phenotype of HCL was most characteristic while the phenotype of CC was sufficiently distinct to confirm that it was a separate disease but not to define its relation to normal B-cell development.

The diseases had significant differences in their clinical features, im-munoglobulin levels and phenotype but no particular pattern was uniformly associated with any disease. Stcpwise, discriminant analysis showed that, using the clinical and phenotypic data together resulted in a more accurate discrimination between the disease than either data set used alone. The extent of expression of CDS, MRBCr, CD10 and CD38 were most useful in distinguishing between the diseases.

Phentotypic heterogeneity was observed in each disease but could be assessed in most detail in CLL because of the larger number of cases. Multiple positive correlations were observed between the expression of pairs of antigens. No particular patterns were detectable linking these correlated pairs. Some cases of CLL had a phentotype similar to that of HCL suggesting that part of the heterogeneity was due to the degree of differentiation and activation of particular malignant clones.

Cases of CLL with a total lymphocyte count less than 10 x 109/1 had more frequent expression of CD38 while those with isolated splenomegaly had more frequent expression of CD25 than other cases. This suggests that some of the clinical heterogeneity of CLL may be due to the homing behaviour of different lymphocyte clones which in turn may be mediated through cell surface antigens.

Cases which expressed any of several antigens (notably MRBCr, CD20, CD23, CD39) on a small proportion of cells had more extensive disease, more advanced disease stage and a worse prognosis. Such cases also more frequently co-expressed slgD and slgM. Multivariate survival analysis showed that, after allowing for the effect of clinical parameters, only MRBCr and MHC class II expression had additional independent prognostic significance. The hypothesis is proposed that, during the course of CLL, the disease evolves with the development of more extensive disease, a fall in the frequency of expression of a number of antigens and a worsening prognosis. This may occur in association with prolymphocytoid transformation but is not necessarily caused by it.

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