title: 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.
abstract: 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.
authors.affiliation: Department of Haematology, School of Medicine, Cardiff University, Heath Park, Cardiff, UK.
authors.forename: Thet Thet
authors.initials: TT
authors.lastname: Lin
authors.forename: Saman
authors.initials: S
authors.lastname: Hewamana
authors.forename: Rachel
authors.initials: R
authors.lastname: Ward
authors.forename: Hannah
authors.initials: H
authors.lastname: Taylor
authors.forename: Tammy
authors.initials: T
authors.lastname: Payne
authors.forename: Guy
authors.initials: G
authors.lastname: Pratt
authors.forename: Duncan
authors.initials: D
authors.lastname: Baird
authors.forename: Chris
authors.initials: C
authors.lastname: Fegan
authors.forename: Chris
authors.initials: C
authors.lastname: Pepper
mesh_terms: D051997:ADP-ribosyl Cyclase 1; D000368:Aged; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000096:biosynthesis; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics; D013601:T-Lymphocytes / Q000201:enzymology / Q000378:metabolism*; D019098:Telomerase / Q000032:analysis; D016615:Telomere / Q000648:ultrastructure
chemical_list: D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019098:Telomerase; D051997:ADP-ribosyl Cyclase 1