Highly similar genomic landscapes in monoclonal B-cell lymphocytosis and ultra-stable chronic lymphocytic leukemia with low frequency of driver mutations.

Highly similar genomic landscapes in monoclonal B-cell lymphocytosis and ultra-stable chronic lymphocytic leukemia with low frequency of driver mutations. Haematologica. 2018 Feb 15;: Authors: Agathangelidis A, Ljungström V, Scarfò L, Fazi C, Gounari M, Pandzic T, Sutton LA, Stamatopoulos K, Tonon G, Rosenquist R, Ghia P Abstract Despite the recent discovery of recurrent driver mutations in chronic lymphocytic leukemia, the genetic factors involved in disease onset remain largely unknown. To address this issue, we performed whole-genome sequencing in 11 individuals with monoclonal B-cell lymphocytosis, both of the low-count and high-count subtypes, and 5 patients with ultra-stable chronic lymphocytic leukemia (>10 years without progression from initial diagnosis). All three entities were indistiguishable at the genomic level exhibiting low genomic complexity and similar types of somatic mutations. Exonic mutations were infrequently identified in putative chronic lymphocytic leukemia driver genes in all settings including low-count monoclonal B-cell lymphocytosis. To corroborate these findings we also performed deep-sequencing in 11 known frequently mutated genes in an extended cohort of 28 monoclonal B-cell lymphocytosis/chronic lymphocytic leukemia cases. Interestingly, shared mutations were detected between clonal B cells and paired polymorphonuclear cells, strengthening the notion that at least a fraction of somatic mutations...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research