Normal serum protein electrophoresis and mutated IGHV genes detect very slowly evolving chronic lymphocytic leukemia patients.

More than 35 years after the Binet classification, there is still a need for simple prognostic markers in chronic lymphocytic leukemia (CLL). Here, we studied the treatment-free survival (TFS) impact of normal serum protein electrophoresis (SPE) at diagnosis. One hundred twelve patients with CLL were analyzed. The main prognostic factors (Binet stage; lymphocytosis; IGHV mutation status; TP53, SF3B1, NOTCH1, and BIRC3 mutations; and cytogenetic abnormalities) were studied. The frequencies of IGHV mutation status, cytogenetic abnormalities, and TP53, SF3B1, NOTCH1, and BIRC3 mutations were not significantly different between normal and abnormal SPE. Normal SPE was associated with Binet stage A, nonprogressive disease for 6 months, lymphocytosis below 30 G/L, and the absence of the IGHV3-21 gene rearrangement which is associated with poor prognosis. The TFS of patients with normal SPE was significantly longer than that of patients with abnormal SPE (log-rank test: P = 0.0015, with 51% untreated patients at 5.6 years and a perfect plateau afterward vs. a median TFS at 2.64 years for abnormal SPE with no plateau). Multivariate analysis using two different Cox models and bootstrapping showed that normal SPE was an independent good prognostic marker for either Binet stage, lymphocytosis, or IGHV mutation status. TFS was further increased when both normal SPE and mutated IGHV were present (log-rank test: P = 0.008, median not reached, plateau at 5.6 years and 66% untreated patients). A comparison with other prognostic markers suggested that normal SPE could reflect slowly advancing CLL disease. Altogether, our results show that a combination of normal SPE and mutated IGHV genes defines a subgroup of patients with CLL who evolve very slowly and who might never need treatment.

Evolutionary history of LTR-retrotransposons among 20 Drosophila species.

BACKGROUND: The presence of transposable elements (TEs) in genomes is known to explain in part the variations of genome sizes among eukaryotes. Even among closely related species, the variation of TE amount may be striking, as for example between the two sibling species, Drosophila melanogaster and D. simulans. However, not much is known concerning the TE content and dynamics among other Drosophila species. The sequencing of several Drosophila genomes, covering the two subgenus Sophophora and Drosophila, revealed a large variation of the repeat content among these species but no much information is known concerning their precise TE content. The identification of some consensus sequences of TEs from the various sequenced Drosophila species allowed to get an idea concerning their variety in term of diversity of superfamilies but the used classification remains very elusive and ambiguous. RESULTS: We choose to focus on LTR-retrotransposons because they represent the most widely represented class of TEs in the Drosophila genomes. In this work, we describe for the first time the phylogenetic relationship of each LTR-retrotransposon family described in 20 Drosophila species, compute their proportion in their respective genomes and identify several new cases of horizontal transfers. CONCLUSION: All these results allow us to have a clearer view on the evolutionary history of LTR retrotransposons among Drosophila that seems to be mainly driven by vertical transmissions although the implications of horizontal transfers, losses and intra-specific diversification are clearly also at play.