title: A 20 Year Clinical and Laboratory Study of Familial B-Chronic Lymphocytic Leukemia in a Single Kindred.
abstract: Four siblings and a parent in a single kindred had documented blood and marrow lymphocytosis during the past 18 to 20 years consistent with chronic lymphocytic leukemia (CLL). Of the four siblings, one developed a spontaneous remission; one died secondary to subepiglotitis with sepsis; one died with prolymphocytoid transformation and one remains alive with splenomegalic CLL. Lymphadenopathy and splenomegaly were variable as was the clinical response to chemotherapy. Bone marrow morphology was initially nodular but progessed to diffuse patterns in both deceased siblings. Blood lymphocyte morphology was extremely variable as were cell doubling times and cytogenetic studies. ABO and HLA typing revealed no evidence of linkage. Immunophenotypic analysis of the B lymphocytes demonstrated a CD19 +, CD20-, CD5 +, Leu8-, Kappa + and a CD19 +, CD20 +, CD5 +, Leu8 +, Kappa + monoclonal lymphocytosis in two affected members. An unaffected sibling showed a CD4 lymphocytosis. VHV and VHII gene sequences were previously described in this kindred (PNAS 84: 8563, '87). We speculate that a CD5 B cell and CD4 T cell lymphocytosis may arise early in this disease followed by the development of a pleomorphic, monoclonal lymphocytosis. The subsequent oligomorphic, monoclonal lymphocytosis shows genotypic, immunophenotypic and some morphological heterogeneity consistent with ongoing differentiation. The longitudinal investigation of familial CLL offers a unique opportunity to study the sequence of events related to the natural history of B-CLL.
authors.affiliation: a Family Studies Section, Epidemiology and Biostatistics Program, NCI, NIH, 439E Executive Plaza North, Bethesda, Maryland, USA.
authors.forename: N E
authors.initials: NE
authors.lastname: Caporaso
authors.affiliation: a Family Studies Section, Epidemiology and Biostatistics Program, NCI, NIH, 439E Executive Plaza North, Bethesda, Maryland, USA.
authors.forename: J
authors.initials: J
authors.lastname: Whitehouse
authors.affiliation: b Laboratory of Cellular and Molecular Biology, Division of Biochemistry and Biophysics, CBER, FDA, NIH Bdg 29, Rm 502, Bethesda, Maryland, USA.
authors.forename: P
authors.initials: P
authors.lastname: Bertin
authors.affiliation: a Family Studies Section, Epidemiology and Biostatistics Program, NCI, NIH, 439E Executive Plaza North, Bethesda, Maryland, USA.
authors.forename: C
authors.initials: C
authors.lastname: Amos
authors.affiliation: c Clinical Chemistry, CPD, CC, NIH, Bethesda, Maryland, USA.
authors.forename: N
authors.initials: N
authors.lastname: Papadopoulos
authors.affiliation: d Division of Virology, CBER, FDA, Bethesda, Maryland, USA.
authors.forename: J
authors.initials: J
authors.lastname: Muller
authors.affiliation: e Cytogenetic Oncology, Medicine Branch, NCI, Bethesda, Maryland, USA.
authors.forename: J
authors.initials: J
authors.lastname: Whang-Peng
authors.affiliation: a Family Studies Section, Epidemiology and Biostatistics Program, NCI, NIH, 439E Executive Plaza North, Bethesda, Maryland, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Tucker
authors.affiliation: f Immunology Service, CPD, CC, NIH, Bethesda, Maryland, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Fleisher
authors.affiliation: b Laboratory of Cellular and Molecular Biology, Division of Biochemistry and Biophysics, CBER, FDA, NIH Bdg 29, Rm 502, Bethesda, Maryland, USA.
authors.forename: G E
authors.initials: GE
authors.lastname: Marti
keywords: B-CLL; CLL; Family studies; lymphocytic leukemia; single kindred