title: Telomerase and telomere length in multiple myeloma: correlations with disease heterogeneity, cytogenetic status, and overall survival.
abstract: 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.affiliation: Laboratory of Developmental Hematopoiesis, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Kai-Da
authors.initials: KD
authors.lastname: Wu
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Orme
authors.forename: John
authors.initials: J
authors.lastname: Shaughnessy
authors.forename: Joth
authors.initials: J
authors.lastname: Jacobson
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
authors.forename: Malcolm A S
authors.initials: MA
authors.lastname: Moore
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D002869:Chromosome Aberrations; D002882:Chromosomes, Human, Pair 13; D020732:Cytogenetic Analysis; D005260:Female; D006098:Granulocytes / Q000648:ultrastructure; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008214:Lymphocytes / Q000648:ultrastructure; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D009101:Multiple Myeloma / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000648:ultrastructure; D010950:Plasma Cells / Q000276:immunology / Q000648:ultrastructure; D011379:Prognosis; D011509:Proteoglycans / Q000032:analysis; D015996:Survival Rate; D053668:Syndecan-1; D053667:Syndecans; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000648:ultrastructure*; D001613:beta 2-Microglobulin / Q000097:blood
chemical_list: D015850:Interleukin-6; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; D001613:beta 2-Microglobulin; D019098:Telomerase