Highly purified CD38+ sub-populations show no evidence of preferential clonal evolution despite having increased proliferative activity when compared with CD38- sub-populations derived from the same CLL patient.

In agreement with a recently published manuscript, this present study demonstrated that CD38+ sub‐populations had increased proliferative activity as evidenced by higher Ki‐67 expression (P < 0·0001). This raised the possibility that the CD38+ fraction is exposed to an increased risk of clonal evolution. However, serial fluorescence in situ hybridisation analysis of highly purified CD38+ and CD38− sub‐populations from individual patients revealed no distinct cytogenetic lesions or evidence of preferential clonal evolution in the CD38+ fractions when compared with their CD38− counter‐parts (P = 0·13). Furthermore, telomere length analysis revealed that all of the sub‐populations had similarly short telomeres (P = 0·31) and comparably low telomerase (TERT) expression (P = 0·75) and telomerase activity (P = 0·88). Subsequent examination of cell‐sorted CD38+ and CD38− sub‐populations from paired peripheral blood and bone marrow samples taken on the same day showed no significant difference in CD38, Ki‐67, TERT expression or telomere lengths, indicating that these chronic lymphocytic leukaemia cells were derived from a single pool trafficking between these two compartments. Taken together, our data show that chronic lymphocytic leukaemia cells derived from bimodal patients all have extensive proliferative histories and have undergone a similar number of cell divisions that is mirrored by the episodic expression of CD38.