ABSTRACT
B-cell chronic lymphocytic leukemia (CLL) had long been recognized as a morpholog-
ically homogeneous disease of mature, resting B lymphocytes. CLL cells are
characterized by the expression of the cell surface antigens CD5, CD23, and CD27,
and low level of surface immunoglobulin (Ig), a pattern not observed on any normal B cell
(1,2). Despite their uniform histological appearance, however, CLL cases turned out to be
surprisingly heterogeneous. First, the rearranged Ig variable region (IgV) genes of CLL
cases can be either somatically mutated or unmutated (3-5), implying that the
corresponding precursor cells may originate from either T cell-dependent or T cell-
independent responses. In addition, there is a correlation between the IgV mutational
status and clinical course (6,7); thus, somatically mutated CLL cases generally show a
better prognosis than unmutated CLL. Second, CLL cases can differ in their
immunophenotype, e.g., by their differential expression of the CD38 cell surface antigen
(6,8,9). Third, CLL exhibits genetic lesions that are distinct from those observed in other
malignancies of mature B cells, such as reciprocal balanced chromosome translocations.
CLL show various genomic alterations, mostly chromosomal deletions (10), which are
more typical of non-hematological tumors. As yet no common genetic lesion has been
identified for CLL. Taken together, the unique phenotypic and genetic characteristics of
CLL do not allow a conclusive assignment of this tumor to a particular cell of origin or to
understand the mechanisms involved in its pathogenesis.
