Monoclonal B-cell lymphocytosis in first-degree relatives of patients with sporadic (non-familial) chronic lymphocytic leukaemia (original) (raw)

2009, British Journal of Haematology

Although chronic lymphocytic leukaemia (CLL) represents one of the most frequent haematological malignancies around the world, accounting for 22-30% of all leukaemias (Redaelli et al, 2004) its aetiology remains largely unknown. In contrast with other forms of leukaemia, the association of CLL with ionizing radiation, chemical exposure and lifestyle factors is only weak (Linet et al, 2007). On the other hand, there is a large amount of evidence, based on epidemiological and family studies, that points to an inherited predisposition and, in fact, CLL exhibits one of the strongest familial predisposition (Caporaso et al, 2007). Recently, the International Familial CLL Consortium defined monoclonal B-cell lymphocytosis (MBL) as the presence of a clonal B-cell population in the context of an absolute B-cell count <5 • 10 9 cells/l, no history of autoimmune disease and no evidence of lymphadenopathy and organomegaly on physical examination (Marti et al, 2005). The biological proximity between CLL and MBL occurs at various levels: immunophenotypically, MBL cells express the surface antigens CD5, CD23 and CD20 dim , which is a typical finding of CLL cells. Moreover, protein expression profile shows that CLL and MBL are identical even when those diagnostic markers are excluded. Finally, the proportion of CD5 + CD23 + MBL cases that have a 13q14 deletion or trisomy 12 is similar to that detected in CLL (Rawstron et al, 2007). Nevertheless, the clinical relationship between MBL and CLL is not fully understood. Thus, Landgren et al (2009) conducted a prospective study where 44 of 45 CLL cases diagnosed in subjects who participated on the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial were preceded by MBL, which suggested MBL as a precursor state. On the other hand, Dagklis et al (2009), at a different level of investigation,