Clone Emergence and Evolution in Chronic Lymphocytic Leukemia: Characterization of Clinical, Laboratory and Immunophenotypic Profiles of 25 Patients

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease usually involving B-cells. Characteristically, B-CLL cells express CD5, CD19, CD20, CD23, cCLLa, Fc and mouse RBC receptors, and low density monoclonal surface immunoglobulins (Moslgs). In order to shed light into the presentation and natural history of B-CLL, patients with a sustained, mild relative (>45%) or absolute lymphocytosis (<104/μL) and a non-diagnostic marrow (waived if lymphocyte count <5 × 103μL) were phenotyped in search of a B-cell clone. Immunophenotyping, initially done by fluorescence microscopy was confirmed by one and two color flow cytometry. Positive and negative controls included 95 patients with overt B-CLL and 45 healthy volunteers, respectively. While patients with overt B-CLL exhibited a cCLLa+ (100%), CD19+ (92%), MosIgs+ (92%) and CD5+ (80%) clone, healthy volunteers did not. Out of 39 patients with lymphocytosis of unknown significance (LUS), 15 had relatively normal immunophenotypes. However, 24 exhibited a cCLLa+ (100%), CD19+ (100%), MosIg+ (96%) and CD5+ (70%) clone including one that followed a polyclonal B-cell proliferation lasting 4 years. In a 25th case, a B-cell clone was detected in one individual presenting with AIHA but normal CBC and marrow. Patients with LUS exhibiting a B-cell clone (LUS-BC) were younger than B-CLL patients. However, except for extent of tumor burden, their clinical, hematologic, immunologic and immunophenotypic profiles were comparable. These observations, suggesting different stages of the same underlying process, are supported by disease progression in one third of patients with lymphocyte counts < 104/μL (whether LUS-BC or stage 0 B-CLL) over an average 4.5 year observation period. Our data confirm the diagnostic value of cCLLa detection and extend the identifiable spectrum of B-CLL to its preclinical stage.