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Publications (3)17.09 Total impact

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    Article: Monoclonal B-cell lymphocytosis (MBL) with normal lymphocyte counts is associated with decreased numbers of normal circulating B-cell subsets.
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    ABSTRACT: Monoclonal B-cell lymphocytosis (MBL) with normal lymphocyte counts is associated with decreased numbers of normal circulating B-cell subsets.Little is known about the distribution of normal lymphoid cells and their subsets in the peripheral blood (PB) of subjects with monoclonal B-cell lymphocytosis (MBL). In our study, we compared the absolute number of PB lymphoid cells and their subpopulations in 95 MBL cases with normal lymphocyte counts vs. 617 age-/sex-matched non-MBL healthy subjects (controls), using highly sensitive flow cytometry. MBL cases showed significantly reduced numbers of normal circulating B-cells, at the expense of immature and naive B-cells; in addition, CD4+CD8+ double-positive T-cells and CD8+ T-cells were significantly lower and higher vs. controls, respectively. Moreover, most normal B-cell subsets were significantly decreased in PB at >1% MBL-counts, vs. "low-count" MBL cases, and lower amounts of immature/naive B-cells were detected in biclonal (particularly in cases with coexisting CLL-like- and non-CLL-like B-cell clones) vs. monoclonal MBL subjects. In summary, our results show imbalanced (reduced) absolute numbers of recently produced normal circulating B-cells (e.g., immature and naıve B-cells) in MBL, which becomes more pronounced as the MBL cell count increases.
    American Journal of Hematology 03/2012; 87(7):721-4. · 4.67 Impact Factor
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    Article: Non-CLL-like monoclonal B-cell lymphocytosis in the general population: prevalence and phenotypic/genetic characteristics.
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    ABSTRACT: Monoclonal B-cell lymphocytosis (MBL) indicates <5 × 10(9) peripheral blood (PB) clonal B-cells/L in healthy individuals. In most cases, MBL cells show similar phenotypic/genetic features to chronic lymphocytic leukemia cells-CLL-like MBL-but little is known about non-CLL-like MBL. PB samples from 639 healthy individuals (46% men/54% women) >40 years old (62 ± 13 years) with normal lymphocyte counts (2.1 ± 0.7 × 10(9)/L) were immunophenotyped using high-sensitive flow cytometry, based on 8-color stainings and the screening for >5 × 10(6) total PB leukocytes. Thirteen subjects (2.0%; 9 males/4 females, aged 73 ± 10 years; absolute lymphocyte count: 2.4 ± 0.8 × 10(9)/L) showed a non-CLL-like clonal B-cell population, whose frequency clearly increased with age: 0.4%, 3%, and 5.4% of subjects aged 40-59, 60-79, and ≥80 years, respectively. One single B-cell clone was detected in 9/13 cases, while two B-cell clones were found in 4/13 (n = 17 MBL populations). Nine MBL cell populations showed a CD5(-) phenotype (usually overlapping with marginal zone-derived (MZL) or lymphoplasmacytic (LPL) non-Hodgkin lymphoma (NHL) B-cells, or an unclassifiable NHL), but CD5(-/+d) (n = 3) and CD5(+) (n = 3 non-CLL-like MBL, consistent with a mantle-cell lymphoma (MCL)-like phenotype, and n = 2 CLL-like) MBL were also identified; iFISH supported the diagnosis in most cases. No preferential IGHV usage of B-cell receptor could be found. Twelve cases reevaluated at month +12 showed circulating clonal B-cells, at mean levels significantly higher than those initially detected. Non-CLL-like MBL cases frequently show biclonality, in association with MZL-, LPL-, MCL-like, or unclassifiable phenotypic profiles. As with CLL-like MBL, the frequency of non-CLL-like MBL increases with age, with a clear predominance of males.
    Cytometry Part B Clinical Cytometry 01/2010; 78 Suppl 1:S24-34. · 2.53 Impact Factor
  • Article: Increased frequency (12%) of circulating chronic lymphocytic leukemia-like B-cell clones in healthy subjects using a highly sensitive multicolor flow cytometry approach.
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    ABSTRACT: Monoclonal B-cell lymphocytosis (MBL) indicates the presence of less than 5 x 10(9)/L circulating monoclonal B cells in otherwise healthy subjects. Recently, it has been reported that circulating chronic lymphocytic leukemia (CLL)-like B cells can be detected using 4- or 5-multicolor flow cytometry in 5% to 7% of adults with normal lymphocyte counts. We investigated the frequency of circulating monoclonal B cells in 608 healthy subjects older than 40 years with normal blood counts, using a highly sensitive 8-color flow cytometry approach and systematic screening for total PB leukocyte count higher than 5 x 10(6). We show that the frequency of PB monoclonal B cells is markedly higher than previously reported (12% for CLL-like B cells, found at frequencies of 0.17 +/- 0.13 x 10(9) cells/L), the incidence progressively increasing with age. Most cases (62%) showed clonal B-cell levels below the maximum sensitivity of the techniques described by others (< 0.01%), supporting the notion that detection of MBL may largely depend on the sensitivity of the flow cytometry approach used.
    Blood 05/2009; 114(1):33-7. · 9.90 Impact Factor