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. [ABSTRACT FROM AUTHOR]