title: Mutational analysis of the cell cycle inhibitor Kip1/p27 in childhood leukemia.
abstract: BACKGROUND
  Cyclin-dependent kinases (CDKs) and cyclins, their regulatory subunits, govern cell-cycle progression in eukaryotic cells. Kip1/p27 is the main cyclin-dependent kinase inhibitor, which arrests cell division inhibiting G1-S transition. Kip1/p27 seems to play a critical role in the pathogenesis of several human malignancies and its lower expression has been shown to correlate with a poor prognosis in adult solid tumors.
  
  
  METHODS
  Bone marrow blasts from 49 children with leukemia, 37 acute lymphoblastic leukemia (ALL), and 12 acute myeloid leukemia (AML) were studied. Exon 3 of Kip1/p27 was amplified using the polymerase chain reaction technique (PCR). Single strand conformational polymorphism and heterodouplex analysis were performed to detect DNA sequence with altered conformations and were subsequently sequenced to document mutations.
  
  
  RESULTS
  Mutations in Kip1/p27 gene were detected in 2 out of 3 T-ALL, 6 out of 12 AML patients, and only 1 out of 34 B lineage ALL cases. Although the patient groups are small, a highly significant relation of the mutation status with the type of leukemia (P = 0.0037) and the risk group according to treatment protocols (P = 0.00021) was estimated. A statistically significant difference in the white blood count was observed (P = 0.019) between the mutated and non-mutated patient groups although no statistically significant association of the mutation status with the hemoglobin and platelets values, karyotype, age, sex, disease progression, and outcome was determined.
  
  
  CONCLUSIONS
  Based upon these results, the Kip1/p27 mutations should be considered for further prospective testing as an additional parameter for risk stratification and treatment of childhood leukemia.
authors.affiliation: Department of Pediatric Hematology-Oncology, University of Crete, Medical School, Heraklion Crete, Greece.
authors.forename: E-A
authors.initials: EA
authors.lastname: Markaki
authors.forename: E
authors.initials: E
authors.lastname: Stiakaki
authors.forename: A
authors.initials: A
authors.lastname: Zafiropoulos
authors.forename: D A
authors.initials: DA
authors.lastname: Arvanitis
authors.forename: N
authors.initials: N
authors.lastname: Katzilakis
authors.forename: H
authors.initials: H
authors.lastname: Dimitriou
authors.forename: D A
authors.initials: DA
authors.lastname: Spandidos
authors.forename: M
authors.initials: M
authors.lastname: Kalmanti
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D014408:Biomarkers, Tumor / Q000235:genetics*; D001853:Bone Marrow / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D009154:Mutation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27