title: Deletions of p15 and/or p16 genes as a poor-prognosis factor in adult T-cell leukemia.
abstract: OBJECTIVE
  To determine the frequency of the deletions of p15/p16 genes in adult T-cell leukemia (ATL) cells and to evaluate their value in the diagnosis of clinical subtypes of ATL patients and the prediction of their clinical outcome.
  
  
  METHODS
  Peripheral-blood samples from 114 patients with ATL were examined by Southern blot analysis. In five chronic-type patients who showed disease progression to acute type, serial samples also were examined.
  
  
  RESULTS
  Among 114 patients, 28 (24.6%) showed the deletions of p15 and/or p16 genes. The results were well correlated with the clinical subtypes. Patients with deleted p15 and/or p16 genes had significantly shorter survival times than the patients in whom both genes were preserved (P < .0001). A similar decline in survival time was observed in the analyses within the same subtypes. In multivariate analysis using the Cox proportional hazard model, the deletions of p15 and/or p16 genes emerged as an independent prognostic indicator. Moreover, three of the five chronic-type patients who progressed to acute type lost the p16 gene alone or both the p15 and p16 genes at their exacerbation phase.
  
  
  CONCLUSIONS
  The results suggest the following: (1) that the deletions of p15 and/or p16 genes play a key role in the progression of ATL; and (2) that these deletions are reliable prognostic factors that predict shortened survival times.
authors.affiliation: Department of Laboratory Medicine, Nagasaki University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Hatta
authors.forename: K
authors.initials: K
authors.lastname: Murata
authors.forename: K
authors.initials: K
authors.lastname: Sugawara
authors.forename: S
authors.initials: S
authors.lastname: Ikeda
authors.forename: M
authors.initials: M
authors.lastname: Mine
authors.forename: T
authors.initials: T
authors.lastname: Maeda
authors.forename: Y
authors.initials: Y
authors.lastname: Hirakata
authors.forename: S
authors.initials: S
authors.lastname: Kamihira
authors.forename: K
authors.initials: K
authors.lastname: Tsukasaki
authors.forename: S
authors.initials: S
authors.lastname: Ogawa
authors.forename: H
authors.initials: H
authors.lastname: Hirai
authors.forename: H P
authors.initials: HP
authors.lastname: Koeffler
authors.forename: M
authors.initials: M
authors.lastname: Tomonaga
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D002452:Cell Count; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D003937:Diagnosis, Differential; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006801:Humans; D015461:Leukemia, Prolymphocytic, T-Cell / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D016016:Proportional Hazards Models; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins
chemical_list: C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025521:Tumor Suppressor Proteins