Leukemia Research Vol. 17, No. 3, pp. 209-216, 1993. 0145-2126/93 $6.00 + .00 Printed in Great Britain. © 1993 Pergamon Press Ltd EXPRESSION OF CD45 ISOFORMS IN CHRONIC B-CELL LEUKAEMIAS HEDDY ZOLA,* NAOMI SIDERIUS,* LORETTA FLEGO,* ROSEMARY SPARROW,t MARTIN B. VAN DER WEYDEN,t JOY NIMMO,~ DEREK N. J. HART,:~ SUE HOUGHTON§and ANDREW W. BOYDII *Department of Clinical Immunology, Flinders Medical Centre and Flinders University, Adelaide, Australia; tDepartment of Haematology, Alfred Hospital, Melbourne, Australia; :~Department of Haematology, Christchurch Hospital, Christchurch, New Zealand; §Department of Diagnostic Haematology, Royal Melbourne Hospital, Melbourne, Australia; IIWalter and Eliza Hall Institute for Medical Research, Melbourne, Australia (Received 21 July 1992. Revision accepted 8 November 1992) Abstract---CD45 isoform expression was studied in 204 cases of B-cell lymphoproliferative disease, including 162 chronic lymphocytic leukaemia (CLL). In almost half the samples tested, CD45R0 was co-expressed with CD45RA, unlike normal B-cells, which express only CD45RA, except at terminal stages of differentiation. In a small number of cases CD45R0 was the dominant isoform expressed. No correlation could be discerned either with Binet or RAI staging in CLL or with disease type CLL, prolymphocytic leukaemia (PLL) or hairy cell leukaemia (HCL). Comparison of CD45 isoform expression with other markers showed no correlation with apparent maturational status of the cells involved. Key words: CD45, CLL, B-cell leukaemia, leukocyte-common antigen. INTRODUCTION CD45 DEFINES a family of monoclonal antibodies directed against different epitopes on a group of related glycoproteins referred to as the leukocyte- common antigen (LCA) or as CD45 [1-3]. Different isoforms of CD45, derived from the same gene by alternative splicing of mRNA, are expressed on cell surfaces [2,4]. CD45R0 (p180) and CD45RA (p205,220) have been most intensively studied because CD45R0 is widely regarded as a marker for memory T-cells [2, 5]. The cytoplasmic domain of CD45 is a tyrosine phosphatase [3, 6] but the func- tions of the different extracellular isoforms are not understood. B-cells generally express CD45RA, although CD45R0 is expressed on some highly dif- ferentiated B-cells [7-9]. However, unlike T-cells, there is no evidence that CD45R0 is a marker of memory B-cells. We have previously reported CLL cells which unexpectedly showed strong expression of CD45R0 Abbreviations: CLL, chronic lymphocytic leukaemia; F1TC, fluorescein isothiocyanate; HCL, hairy-cell leu- kaemia; NHL, non-Hodgkin's lymphoma; PE, phyco- erythrin; PLL, prolymphocytic leukaemia. Correspondence to: Professor H. Zola, Department of Clinical Immunology, Flinders Medical Centre, Bedford Park, SA 5042, Australia. 209 and weak expression of CD45RA [8]. Other CLL samples had the typical B-cell CD45 phenotype, with CD45RA expressed strongly and CD45R0 not expressed, and the intermediate phenotype, with CD45RA and R0 isoforms expressed about equally, was found in the remaining samples. Earlier studies, using immunochemical methods, had shown that the expression of the different chains of CD45 was het- erogeneous in B-cell leukaemia and lymphoma [10- 12]. Maddy et al. [13] studied a group of 90 B-CLL, classified by immunochemical methods as expressing predominantly high- or low-molecular weight iso- forms of CD45, and showed that surface staining with CD45RA and R0 antibodies correlated with the immunochemical data. Maddy et al. [13, 14[ found that the intensity of staining for CD45RA correlated with staining intensities for CD20, CD21, CD22 and surface Ig, and suggested that CLLs with higher CD45RA represent less mature cells. The purpose of this study was initially to extend our earlier observations [8] by studying a large panel of patients and to examine the relationship between CD45 isoform expression and maturational status of B-cells suggested by Maddy et al. [13, 14], since our study had suggested at best an equivocal relationship between maturational state and CD45R0 expression in normal B-cells [8]. Finally, we sought to identify