Abstract
Patients with B-cell chronic lymphocytic leukemia (B-CLL) segregate into sub-groups with very different survival times. Because clinical observations suggest that leukemic cells accumulate at different rates, we measured telomere length and telomerase activity in B-CLL cells to distinguish differences in cellular replication. Our data indicate that the telomeres of B-CLL cells are shorter than telomeres of B cells from healthy subjects, indicating that the leukemic cells have a prolonged proliferative history. Leukemic cells of the immunoglobulin V gene mutation subgroups differ in telomere length and telomerase activity. B lymphocytes from the subgroup with poor outcome and with limited IgV gene mutations have uniformly shorter telomeres and more telomerase activity than those from the subgroup with better outcome and with considerable mutations. Differences in telomere length appear to largely reflect the proliferative histories of precursors of the leukemic cells, although differences in cell division, masked by the action of telomerase, cannot be excluded. These results may provide insight into the stages of maturation and the activation pathways of the cells that give rise to B-CLL. In addition, they reinforce the concept that B-CLL is not simply an accumulative disease of slowly dividing B lymphocytes but possibly one of B cells with extensive proliferative histories.
| Original language | English |
|---|---|
| Pages (from-to) | 375-382 |
| Number of pages | 8 |
| Journal | Blood |
| Volume | 103 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jan 15 2004 |
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ASJC Scopus subject areas
- Hematology
Cite this
Telomere length and telomerase activity delineate distinctive replicative features of the B-CLL subgroups defined by immunoglobulin V gene mutations. / Damle, Rajendra N.; Batliwalla, Franak M.; Ghiotto, Fabio; Valetto, Angelo; Albesiano, Emilia; Sison, Cristina; Allen, Steven L.; Kolitz, Jonathan; Vinciguerra, Vincent P.; Kudalkar, Prasad; Wasil, Tarun; Rai, Kanti R.; Ferrarini, Manlio; Gregersen, Peter K.; Chiorazzi, Nicholas.
In: Blood, Vol. 103, No. 2, 15.01.2004, p. 375-382.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Telomere length and telomerase activity delineate distinctive replicative features of the B-CLL subgroups defined by immunoglobulin V gene mutations
AU - Damle, Rajendra N.
AU - Batliwalla, Franak M.
AU - Ghiotto, Fabio
AU - Valetto, Angelo
AU - Albesiano, Emilia
AU - Sison, Cristina
AU - Allen, Steven L.
AU - Kolitz, Jonathan
AU - Vinciguerra, Vincent P.
AU - Kudalkar, Prasad
AU - Wasil, Tarun
AU - Rai, Kanti R.
AU - Ferrarini, Manlio
AU - Gregersen, Peter K.
AU - Chiorazzi, Nicholas
PY - 2004/1/15
Y1 - 2004/1/15
N2 - Patients with B-cell chronic lymphocytic leukemia (B-CLL) segregate into sub-groups with very different survival times. Because clinical observations suggest that leukemic cells accumulate at different rates, we measured telomere length and telomerase activity in B-CLL cells to distinguish differences in cellular replication. Our data indicate that the telomeres of B-CLL cells are shorter than telomeres of B cells from healthy subjects, indicating that the leukemic cells have a prolonged proliferative history. Leukemic cells of the immunoglobulin V gene mutation subgroups differ in telomere length and telomerase activity. B lymphocytes from the subgroup with poor outcome and with limited IgV gene mutations have uniformly shorter telomeres and more telomerase activity than those from the subgroup with better outcome and with considerable mutations. Differences in telomere length appear to largely reflect the proliferative histories of precursors of the leukemic cells, although differences in cell division, masked by the action of telomerase, cannot be excluded. These results may provide insight into the stages of maturation and the activation pathways of the cells that give rise to B-CLL. In addition, they reinforce the concept that B-CLL is not simply an accumulative disease of slowly dividing B lymphocytes but possibly one of B cells with extensive proliferative histories.
AB - Patients with B-cell chronic lymphocytic leukemia (B-CLL) segregate into sub-groups with very different survival times. Because clinical observations suggest that leukemic cells accumulate at different rates, we measured telomere length and telomerase activity in B-CLL cells to distinguish differences in cellular replication. Our data indicate that the telomeres of B-CLL cells are shorter than telomeres of B cells from healthy subjects, indicating that the leukemic cells have a prolonged proliferative history. Leukemic cells of the immunoglobulin V gene mutation subgroups differ in telomere length and telomerase activity. B lymphocytes from the subgroup with poor outcome and with limited IgV gene mutations have uniformly shorter telomeres and more telomerase activity than those from the subgroup with better outcome and with considerable mutations. Differences in telomere length appear to largely reflect the proliferative histories of precursors of the leukemic cells, although differences in cell division, masked by the action of telomerase, cannot be excluded. These results may provide insight into the stages of maturation and the activation pathways of the cells that give rise to B-CLL. In addition, they reinforce the concept that B-CLL is not simply an accumulative disease of slowly dividing B lymphocytes but possibly one of B cells with extensive proliferative histories.
UR - http://www.scopus.com/inward/record.url?scp=9144245353&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=9144245353&partnerID=8YFLogxK
U2 - 10.1182/blood-2003-04-1345
DO - 10.1182/blood-2003-04-1345
M3 - Article
C2 - 14504108
AN - SCOPUS:9144245353
VL - 103
SP - 375
EP - 382
JO - Blood
JF - Blood
SN - 0006-4971
IS - 2
ER -