Journal
HAEMATOLOGICA
Volume 103, Issue 7, Pages 1198-1208Publisher
FERRATA STORTI FOUNDATION
DOI: 10.3324/haematol.2017.183954
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Funding
- Red Tematica de Investigacion Cooperativa en Cancer (RTICC) (Madrid, Spain) [RD06/0020/0035, RD12/0036/0048]
- Instituto de Salud Carlos III (Madrid, Spain)
- Ministerio de Economia y Competitividad, (Madrid, Spain) [CB16/12/00400]
- CIBERONC, (Madrid, Spain) [CB16/12/00400]
- Instituto de Salud Carlos III (Madrid, Spain) [CB16/12/00400]
- Fondo de Investigacion Sanitaria of Instituto de Salud Carlos III [FIS PI06/0824-FEDER, PS09/02430-FEDER, PI12/00905-FEDER, DTS15/00119-FEDER, PI16/00787-FEDER, PI17/00399-FEDER]
- Gerencia Regional de Salud (Consejeria de Educacion and Consejeria de Sanidad of Castilla y Leon, Valladolid, Spain) [GRS206/A/08, SAN/1778/2009]
- Consejeria de Educacion and Consejeria de Sanidad of Castilla y Leon, Valladolid, Spain [SA079U14]
- Instituto de Salud Carlos III [PTA2014-09963-I]
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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 leukemia-like) 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 B-cell 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.
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