BACKGROUND: Among all hematologic malignancies, B-cell chronic lymphocytic leukemia (BCLL) has the highest familial clustering (three- to sevenfold increase), strongly suggesting a genetic component to its etiology. Familial BCLL can be used as a model to study the early pathogenesis of this disease. METHODS: We examined nine kindreds from the National Cancer Institute's Familial BCLL Registry, consisting of 19 affected members with BCLL and 33 clinically unaffected first-degree relatives. Flow cytometric immunophenotyping to detect a B-cell monoclonal lymphocytosis (BCML) was performed. Monoclonality was confirmed by polymerase chain reaction analysis of whole blood DNA. Cell cycle analysis for aneuploidy was conducted. RESULTS: In all affected individuals, we observed the classic BCLL CD5/CD19/CD20/CD23 immunophenotypic patterns. Six of the 33 unaffected individuals (18%) had evidence of BCML. Additional individuals (13/33, 39%) showed some other abnormality, whereas 14 individuals (42%) were normal. Based on an estimated prevalence of 0.7% for BCML in the general population, the finding of six subjects (18%) with clonal abnormalities in this relatively modest sample was significantly greater than expected (i.e., 18% vs. 0.7%, P < 5.7 x 10(-9)). CONCLUSIONS: Individual components of BCML and other B-cell abnormalities were observed in almost half of the apparently unaffected individuals. Our findings suggested that BCML may be an early detectable abnormality in BCLL. The spectrum of some of these observed abnormalities suggested the involvement of different B-cell subpopulations or different pathways in clonal evolution. Population-based, longitudinal studies will be required to determine the incidence of BCML and other B-cell abnormalities and their relation to disease progression in BCLL and other closely related B-cell lymphoproliferative disorders. Published 2003 Wiley-Liss, Inc.
BACKGROUND: Among all hematologic malignancies, B-cell chronic lymphocytic leukemia (BCLL) has the highest familial clustering (three- to sevenfold increase), strongly suggesting a genetic component to its etiology. Familial BCLL can be used as a model to study the early pathogenesis of this disease. METHODS: We examined nine kindreds from the National Cancer Institute's Familial BCLL Registry, consisting of 19 affected members with BCLL and 33 clinically unaffected first-degree relatives. Flow cytometric immunophenotyping to detect a B-cell monoclonal lymphocytosis (BCML) was performed. Monoclonality was confirmed by polymerase chain reaction analysis of whole blood DNA. Cell cycle analysis for aneuploidy was conducted. RESULTS: In all affected individuals, we observed the classic BCLL CD5/CD19/CD20/CD23 immunophenotypic patterns. Six of the 33 unaffected individuals (18%) had evidence of BCML. Additional individuals (13/33, 39%) showed some other abnormality, whereas 14 individuals (42%) were normal. Based on an estimated prevalence of 0.7% for BCML in the general population, the finding of six subjects (18%) with clonal abnormalities in this relatively modest sample was significantly greater than expected (i.e., 18% vs. 0.7%, P < 5.7 x 10(-9)). CONCLUSIONS: Individual components of BCML and other B-cell abnormalities were observed in almost half of the apparently unaffected individuals. Our findings suggested that BCML may be an early detectable abnormality in BCLL. The spectrum of some of these observed abnormalities suggested the involvement of different B-cell subpopulations or different pathways in clonal evolution. Population-based, longitudinal studies will be required to determine the incidence of BCML and other B-cell abnormalities and their relation to disease progression in BCLL and other closely related B-cell lymphoproliferative disorders. Published 2003 Wiley-Liss, Inc.
Authors: Lynn R Goldin; Mark C Lanasa; Susan L Slager; James R Cerhan; Celine M Vachon; Sara S Strom; Nicola J Camp; Logan G Spector; Jose F Leis; Vicki A Morrison; Martha Glenn; Kari G Rabe; Sara J Achenbach; Sallie D Algood; Fatima Abbasi; Laura Fontaine; Michelle Yau; Laura Z Rassenti; Neil E Kay; Timothy G Call; Curtis A Hanson; J Brice Weinberg; Gerald E Marti; Neil E Caporaso Journal: Br J Haematol Date: 2010-08-25 Impact factor: 6.998
Authors: Youn K Shim; Dannie C Middleton; Neil E Caporaso; Jane M Rachel; Ola Landgren; Fatima Abbasi; Elizabeth S Raveche; Andy C Rawstron; Alberto Orfao; Gerald E Marti; Robert F Vogt Journal: Cytometry B Clin Cytom Date: 2010 Impact factor: 3.058
Authors: Lynn R Goldin; Magnus Björkholm; Sigurdur Y Kristinsson; Ingemar Turesson; Ola Landgren Journal: Haematologica Date: 2009-03-13 Impact factor: 9.941
Authors: Youn K Shim; Jane M Rachel; Paolo Ghia; Jeff Boren; Fatima Abbasi; Antonis Dagklis; Geri Venable; Jiyeon Kang; Heba Degheidy; Fred V Plapp; Robert F Vogt; Jay E Menitove; Gerald E Marti Journal: Blood Date: 2013-12-17 Impact factor: 22.113
Authors: M C Lanasa; S D Allgood; A D Volkheimer; J P Gockerman; J F Whitesides; B K Goodman; J O Moore; J B Weinberg; M C Levesque Journal: Leukemia Date: 2009-10-15 Impact factor: 11.528