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

被引:16
作者
Lin, Thet Thet [1 ]
Hewamana, Saman [1 ]
Ward, Rachel [1 ]
Taylor, Hannah [2 ]
Payne, Tammy [2 ]
Pratt, Guy [3 ]
Baird, Duncan [4 ]
Fegan, Chris [1 ]
Pepper, Chris [1 ]
机构
[1] Cardiff Univ, Sch Med, Dept Haematol, Cardiff CF14 4XN, S Glam, Wales
[2] Llandough Hosp, Dept Haematol, Penarth, S Glam, Wales
[3] Birmingham Heartlands Hosp, Dept Haematol, Birmingham, W Midlands, England
[4] Cardiff Univ, Sch Med, Dept Pathol, Cardiff CF14 4XN, S Glam, Wales
关键词
chronic lymphocytic leukaemia; CD38; telomere length; telomerase; FISH analysis;
D O I
10.1111/j.1365-2141.2008.07236.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:595 / 605
页数:11
相关论文
共 49 条
[1]   The relevance of cytological studies and Ki-67 reactivity to the clinical course of chronic lymphocytic leukemia [J].
Astsaturov, IA ;
Samoilova, RS ;
Iakhnina, EI ;
Pivnik, AV ;
Vorobiov, AI .
LEUKEMIA & LYMPHOMA, 1997, 26 (3-4) :337-342
[2]   Extensive allelic variation and ultrashort telomeres in senescent human cells [J].
Baird, DM ;
Rowson, J ;
Wynford-Thomas, D ;
Kipling, D .
NATURE GENETICS, 2003, 33 (02) :203-207
[3]  
Bechter OE, 1998, CANCER RES, V58, P4918
[4]  
BINET JL, 1981, CANCER-AM CANCER SOC, V48, P198, DOI 10.1002/1097-0142(19810701)48:1<198::AID-CNCR2820480131>3.0.CO
[5]  
2-V
[6]   Intra-allelic mutation at human telomeres [J].
Britt-Compton, B. ;
Baird, D. M. .
BIOCHEMICAL SOCIETY TRANSACTIONS, 2006, 34 :581-582
[7]   In vivo labeling of newly synthesized DNA suggests that the CD38+ fraction is enriched in proliferating cells within a clone of chronic lymphocytic leukemia B cells. [J].
Calissano, Carlo ;
Damle, Rajendra ;
Banapour, Taraneh ;
Cesar, Denise ;
Hellerstein, Marc ;
Allen, Steven ;
Rai, Kanti ;
Chiorazzi, Nicholas .
BLOOD, 2006, 108 (11) :12A-13A
[8]   Cell proliferation and death: Forgotten features of chronic lymphocytic leukemia B cells [J].
Chiorazzi, Nicholas .
BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY, 2007, 20 (03) :399-413
[9]   CD38 expression does not change in B-cell chronic lymphocytic leukemia [J].
D'Arena, G ;
Nunziata, G ;
Coppola, G ;
Vigilotti, ML ;
Tartarone, A ;
Carpinelli, N ;
Matera, R ;
Bisogno, RC ;
Pistolese, G ;
Di Renzo, N .
BLOOD, 2002, 100 (08) :3052-3053
[10]   CD38 expression labels an activated subset within chronic lymphocytic leukemia clones enriched in proliferating B cells [J].
Damle, Rajendra N. ;
Tembumi, Sonal ;
Calissano, Carlo ;
Yancopoulos, Sophia ;
Banapour, Taraneh ;
Sison, Cristina ;
Allen, Steven L. ;
Rai, Kanti R. ;
Chiorazzi, Nicholas .
BLOOD, 2007, 110 (09) :3352-3359