title: Telomere Length Recovery: A Strong Predictor of Overall Survival in Acute Promyelocytic Leukemia.
abstract: Telomeres are the capping ends of chromosomes that protect the loss of genetic material and prevent chromosomal instability. In human tissue-specific stem/progenitor cells, telomere length (TL) is maintained by the telomerase complex, which consists of a reverse transcriptase catalytic subunit (TERT) and an RNA template (TERC). Very short telomeres and loss-of-function mutations in the TERT and TERC genes have been reported in acute myeloid leukemia, but the role of telomeres in acute promyelocytic leukemia (APL) has not been well established. We report the results for a large cohort of 187 PML/RARα-positive APL patients. No germline mutations in the TERT or TERC genes were identified. Codon 279 and 1062 TERT polymorphisms were present at a frequency similar to that in the general population. TL measured in blood or marrow mononuclear cells at diagnosis was significantly shorter in the APL patients than in healthy volunteers, and shorter telomeres at diagnosis were significantly associated with high-risk disease. For patients who achieved complete remission, the median increase in TL from diagnosis to remission (delta TL) was 2.0 kilobase (kb), and we found delta TL to be the most powerful predictor of overall survival when compared with well-established risk factors for poor outcomes in APL.
authors.affiliation: Oncology/Hematology Division, The University of Nebraska Medical Center, Omaha, Nebr., USA.
authors.forename: Muhamed
authors.initials: M
authors.lastname: Baljevic
authors.forename: Bogdan
authors.initials: B
authors.lastname: Dumitriu
authors.forename: Ju-Whei
authors.initials: JW
authors.lastname: Lee
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Paietta
authors.forename: Peter H
authors.initials: PH
authors.lastname: Wiernik
authors.forename: Janis
authors.initials: J
authors.lastname: Racevskis
authors.forename: Christina
authors.initials: C
authors.lastname: Chen
authors.forename: Eytan M
authors.initials: EM
authors.lastname: Stein
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gallagher
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Rowe
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: Bayard L
authors.initials: BL
authors.lastname: Powell
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Steven E
authors.initials: SE
authors.lastname: Coutré
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lancet
authors.forename: Mark R
authors.initials: MR
authors.lastname: Litzow
authors.forename: Selina M
authors.initials: SM
authors.lastname: Luger
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003062:Codon; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011110:Polymorphism, Genetic; D012313:RNA / Q000235:genetics; D015996:Survival Rate; D019098:Telomerase / Q000235:genetics*; D059505:Telomere Homeostasis / Q000187:drug effects / Q000235:genetics*
chemical_list: D003062:Codon; D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; C422952:telomerase RNA; D012313:RNA; C509186:TERT protein, human; D019098:Telomerase