Surface antigen expression in chronic lymphocytic leukemia: clustering analysis, interrelationships and effects of chromosomal abnormalities.
Chronic lymphocytic leukemia (CLL) is a phenotypically distinguishable form of B-lymphoid leukemias. The regularity of surface membrane antigen expression patterns, their interrelationships as well as the effects of the three frequent chromosomal aberrations, ie 11q deletion, 13q deletion and trisomy 12, were investigated in 35 classic CLL cases by flow cytometry. The two-way cluster analysis of 31 individual antigens revealed three expression patterns: (1) most cells in most cases positive (CD5, CD19, CD20, CD23, CD27, CD40, CD45, CD45RA); (2) most cells in most cases negative (CD10, CD14, CD34, CD122, CD154, mIgG); and (3) a mixed pattern with a variable number of positive cases and a variable percentage of positive cells in individual cases (CD11c, CD21, CD22, CD25, CD38, CD45RO, CD79b, CD80, CD95, CD124, CD126, CD130, FMC7, mIgD, mIgkappa, mIglambda, mIgM). The expressions of several antigens were strongly interdependent, even when antigens belonged to entirely different gene families. Such antigen pairs were: CD11c/CD21; CD19/CD45; CD19/CD79b; CD22/CD45RA; CD23/Igkappa; CD25/mIgM; CD27/CD45; CD45/CD79b; CD45RA/Igkappa. In contrast, the expression of some antigens was mutually exclusive, the best examples being CD45RA/CD45RO, CD38/CD80 and CD45RA/CD80. Deletion of chromosome arm 11q attenuated expression of splicing variant CD45RA, but enhanced CD45RO expression. In contrast, cases of trisomy 12 were associated with enhanced CD45RA and attenuated CD45RO expression. Similarly, trisomy 12 was associated with enhanced CD27 and mIgkappa expression. The variable levels of signaling surface membrane antigens, their interactions and interference by genetic aberrations are likely to affect the clinical progression and drug response of CLL.
Hulkkonen
J
J
Department of Microbiology and Immunology, University of Tampere Medical School and Laboratory Center of Tampere University Hospital, Tampere, Finland.
Vilpo
L
L
Hurme
M
M
Vilpo
J
J
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis* / Q000235:genetics; D000943:Antigens, Differentiation / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000235:genetics; D000954:Antigens, Surface / Q000032:analysis* / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000648:ultrastructure; D002881:Chromosomes, Human, Pair 12; D002882:Chromosomes, Human, Pair 13 / Q000648:ultrastructure; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009244:NAD+ Nucleosidase / Q000032:analysis; D014411:Neoplastic Stem Cells / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000032:analysis* / Q000235:genetics; D017384:Sequence Deletion; D014314:Trisomy
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D017493:Leukocyte Common Antigens; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1