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 chronic lymphocytic leukaemia 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.