Document Detail


Telomerase and telomere length in multiple myeloma: correlations with disease heterogeneity, cytogenetic status, and overall survival.
MedLine Citation:
PMID:  12609839     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have investigated the significance of telomerase activity (TA) and telomere length (TL) in multiple myeloma (MM). The analyses were undertaken on CD138+ MM cells isolated from the marrow of 183 patients either at diagnosis or in relapse. There was heterogeneity in telomerase expression; 36% of the patients had TA levels comparable to those detected in normal plasma cells, and 13% of patients had levels 1- to 4-fold greater than in a neuroblastoma cell line control. The TL of MM cells was significantly shorter than that of the patients' own leukocytes; in 25% of patients, the TL measured less than 4.0 kbp. Analysis of TL distribution indicated selective TA-mediated stabilization of shorter telomeres when mean TL fell below 5.5 kbp. Unusually long (10.8-15.0 kbp) telomeres were observed in 7 patients, and low TA was observed in 5 of 7 patients, suggesting the operation of a TA-independent pathway of telomere stabilization. A strong negative correlation existed between TA and TL or platelet count. TL negatively correlated with age and with interleukin-6 (IL-6) and beta2-microglobulin levels. Various cytogenetic abnormalities, including those associated with poor prognosis, strongly correlated with TA and, to a lesser extent, with short TL. High TA and short TL defined a subgroup of patients with poor prognosis. At 1 year the survival rate in patients with TA levels lower than 25% of neuroblastoma control and TL greater than 5.5 kbp was 82%, whereas in patients with higher TA and shorter TL the survival rate was 63% (P =.004). The 2-year survival rate for patients with TA levels lower than 25% was 81%, and it was 52% in those with higher TA levels (P <.0001).
Authors:
Kai-Da Wu; Lisa M Orme; John Shaughnessy; Joth Jacobson; Bart Barlogie; Malcolm A S Moore
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2003-02-27
Journal Detail:
Title:  Blood     Volume:  101     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-06-05     Completed Date:  2004-02-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4982-9     Citation Subset:  AIM; IM    
Affiliation:
Laboratory of Developmental Hematopoiesis, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Aging
Chromosome Aberrations
Chromosomes, Human, Pair 13
Cytogenetic Analysis*
Female
Granulocytes / ultrastructure
Humans
Interleukin-6 / blood
Lymphocytes / ultrastructure
Male
Membrane Glycoproteins / analysis
Middle Aged
Multiple Myeloma* / enzymology,  genetics,  mortality,  ultrastructure
Plasma Cells / immunology,  ultrastructure
Prognosis
Proteoglycans / analysis
Survival Rate
Syndecan-1
Syndecans
Telomerase / metabolism*
Telomere / ultrastructure*
beta 2-Microglobulin / blood
Grant Support
ID/Acronym/Agency:
CA55819/CA/NCI NIH HHS; U19-CA67842/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Interleukin-6; 0/Membrane Glycoproteins; 0/Proteoglycans; 0/SDC1 protein, human; 0/Syndecan-1; 0/Syndecans; 0/beta 2-Microglobulin; EC 2.7.7.49/Telomerase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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