2 research outputs found
Low-count monoclonal B-cell lymphocytosis persists after seven years of follow up and is associated with a poorer outcome
[EN]Low-count monoclonal B-cell lymphocytosis is defined by the presence
of very low numbers of circulating clonal B cells, usually phenotypically
similar to chronic lymphocytic leukemia cells, whose
biological and clinical significance remains elusive. Herein, we re-evaluated
65/91 low-count monoclonal B-cell lymphocytosis cases (54 chronic
lymphocytic leukemia-like and 11 non-chronic lymphocytic leukemialike)
followed-up for a median of seven years, using high-sensitivity
flow cytometry and interphase fluorescence in situ hybridization.
Overall, the clone size significantly increased in 69% of low-count monoclonal
B-cell lymphocytosis cases, but only one subject progressed to
high-count monoclonal B-cell lymphocytosis. In parallel, the frequency
of cytogenetic alterations increased over time (32% vs. 61% of cases,
respectively). The absolute number of the major T-cell and natural killer
cell populations also increased, but only among chronic lymphocytic
leukemia-like cases with increased clone size vs. age- and sex-matched
controls. Although progression to chronic lymphocytic leukemia was
not observed, the overall survival of low-count monoclonal B-cell lymphocytosis
individuals was significantly reduced vs. non-monoclonal Bcell
lymphocytosis controls (P=0.03) plus the general population from
the same region (P≤0.001), particularly among females (P=0.01); infection
and cancer were the main causes of death in low-count monoclonal
B-cell lymphocytosis. In summary, despite the fact that mid-term progression
from low-count monoclonal B-cell lymphocytosis to high-count
monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia
appears to be unlikely, these clones persist at increased numbers, usually
carrying more genetic alterations, and might thus be a marker of an
impaired immune system indirectly associated with a poorer outcome,
particularly among females
Phenotypic profile of expanded NK cells in chronic lymphoproliferative disorders: a surrogate marker for NK-cell clonality
[EN]Currently, the lack of a universal and specific marker of clonality hampers the diagnosis and classification of chronic expansions of natural killer (NK) cells. Here we investigated the utility of flow cytometric detection of aberrant/altered NK-cell phenotypes as a surrogate marker for clonality, in the diagnostic work-up of chronic lymphoproliferative disorders of NK cells (CLPD-NK). For this purpose, a large panel of markers was evaluated by multiparametric flow cytometry on peripheral blood (PB) CD56(low) NK cells from 60 patients, including 23 subjects with predefined clonal (n = 9) and polyclonal (n = 14) CD56(low) NK-cell expansions, and 37 with CLPD-NK of undetermined clonality; also, PB samples from 10 healthy adults were included. Clonality was established using the human androgen receptor (HUMARA) assay. Clonal NK cells were found to show decreased expression of CD7, CD11b and CD38, and higher CD2, CD94 and HLADR levels vs. normal NK cells, together with a restricted repertoire of expression of the CD158a, CD158b and CD161 killer-associated receptors. In turn, NK cells from both clonal and polyclonal CLPD-NK showed similar/overlapping phenotypic profiles, except for high and more homogeneous expression of CD94 and HLADR, which was restricted to clonal CLPD-NK. We conclude that the CD94(hi)/HLADR+ phenotypic profile proved to be a useful surrogate marker for NK-cell clonality.This work has been partially supported by the following grants: FIS 02/1244-FEDER, DTS 15/00119-FEDER, RTICC RD06/0020/0035-FEDER and RTICC RD12/0036/0048-FEDER from the Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain; SA103/03 and SA079U14 from the Consejería de Educación, Junta de Castilla y León, Valladolid, Spain. The research activities of the EuroFlow Consortium were supported
by the European Commission (grant STREP EU-FP6, LSHB-CT-2006–018708, entitled ‘Flow cytometry for fast and sensitive diagnosis and follow-up of hematological malignancies’)