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the progression rate from MBLlo to MBLhi and CLL thus far.10,22,23 Hence, Fazi et al. showed persistent MBLlo clones over time in 90% of CLL-like MBLlo and only 67% of non CLL-like clones, after a median follow-up of ≈3y.10 Herein, we demonstrate the systematic persistence of both CLL- like and non CLL-like MBLlo B-cell clones with an identical phenotype to baseline after seven years follow-up in 65/65 MBLlo cases, confirming that MBLlo is not a transient condition. Similarly, Matos et al. also found the persistence of B-cell clones in their limited series of CLL-like MBLlo cases (n=5) after a median follow-up of ≈7y.23 Interestingly, in 3/56 CLL-like MBLlo cases, the number of clones identi-
fied at seven years follow-up changed, which might sug- gest the emergence of MBLlo from an oligoclonal back- ground that mirrors competition and natural selection among multiple coexisting clones.24 Changes observed in the VDJ sequences of the expanded B cells from most of these cases (data not shown), together with the progressive- ly decreasing rate of oligoclonality from MBLlo (12-19%) to MBLhi (2.9-13%) and CLL (0.7-3.4%), would further support this hypothesis.9,12,25–27 The significance of such oligoclonal B-cell expansions in MBLlo remains unknown, but might be the consequence of the early stages of altered oligoclonal immune responses against multiple antigens,
AB
CD
EF
Figure 2. Overall survival from baseline (mor- tality rates) of MBLlo individuals vs. age- and sex-matched non-MBL controls. Left column panels represent comparisons of overall sur- vival curves from MBLlo subjects (black) and age- and sex-matched non-MBL controls (dotted gray). The same comparison is depicted for all individuals (Panel A) and separately for males (Panel C) and females (Panel E). In the right col- umn, overall survival curves comparing all MBLlo subjects with a CLL-like phenotype vs. all age- and sex-matched non-MBL controls (Panel B). The same subjects distributed according to sex are shown in Panel D (males) and in Panel F (females). MBLlo: low-count monoclonal B-cell lymphocytosis.
haematologica | 2018; 103(7)