PMID- 10935480
OWN - NLM
STAT- MEDLINE
DCOM- 20000817
LR  - 20231213
IS  - 1522-8002 (Print)
IS  - 1476-5586 (Electronic)
IS  - 1476-5586 (Linking)
VI  - 1
IP  - 3
DP  - 1999 Aug
TI  - p27KIP1 deletions in childhood acute lymphoblastic leukemia.
PG  - 253-61
AB  - The p27KIP1 gene, which encodes a cyclin-dependent kinase (CDK) inhibitor, has 
      been assigned to chromosome band 12p12, a region often affected by 
      cytogenetically apparent deletions or translocations in childhood acute 
      lymphoblastic leukemia (ALL). As described here, fluorescence in situ 
      hybridization (FISH) analysis of 35 primary ALL samples with cytogenetic evidence 
      of 12p abnormalities revealed hemizygous deletions of p27KIP1 in 29 cases. 
      Further analysis of 19 of these cases with two additional gene-specific probes 
      from the 12p region (hematopoietic cell phosphatase, HCP and cyclin D2, CCND2) 
      showed that p27KIP1 is located more proximally on the short arm of chromosome 12 
      and is deleted more frequently than either HCP or CCND2. Of 16 of these cases 
      with hemizygous deletion of p27KIP1, only eight showed loss of HCP or CCND2, 
      whereas loss of either of the latter two loci was uniformly associated with loss 
      of p27KIP1. Missense mutations or mutations leading to premature termination 
      codons were not detected in the coding sequences of the retained p27KIP1 alleles 
      in any of the 16 ALL cases examined, indicating a lack of homozygous 
      inactivation. By Southern blot analysis, one case of primary T-cell ALL had 
      hemizygous loss of a single p27KIP1 allele and a 34.5-kb deletion, including the 
      second coding exon of the other allele. Despite homozygous inactivation of p27KP1 
      in this case, our data suggest that haploinsufficiency for p27KIP1 is the primary 
      consequence of 12p chromosomal deletions in childhood ALL. The oncogenic role of 
      reduced, but not absent, levels of p27KIP1 is supported by recent studies in 
      murine models and evidence that this protein not only inhibits the activity of 
      complexes containing CDK2 and cyclin E, but also promotes the assembly and 
      catalytic activity of CDK4 or CDK6 in complexes with cyclin D.
FAU - Komuro, H
AU  - Komuro H
AD  - Department of Experimental Oncology, Howard Hughes Medical Institute, St Jude 
      Children's Research Hospital, Memphis, TN 38105, USA.
FAU - Valentine, M B
AU  - Valentine MB
FAU - Rubnitz, J E
AU  - Rubnitz JE
FAU - Saito, M
AU  - Saito M
FAU - Raimondi, S C
AU  - Raimondi SC
FAU - Carroll, A J
AU  - Carroll AJ
FAU - Yi, T
AU  - Yi T
FAU - Sherr, C J
AU  - Sherr CJ
FAU - Look, A T
AU  - Look AT
LA  - eng
GR  - P01 CA071907/CA/NCI NIH HHS/United States
GR  - CA 25408/CA/NCI NIH HHS/United States
GR  - CA 31566/CA/NCI NIH HHS/United States
GR  - CA 71907/CA/NCI NIH HHS/United States
GR  - P30 CA021765/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neoplasia
JT  - Neoplasia (New York, N.Y.)
JID - 100886622
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Proto-Oncogene Proteins c-ets)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
SB  - IM
MH  - Adolescent
MH  - Base Sequence
MH  - Blotting, Southern
MH  - *Cell Cycle Proteins
MH  - Child
MH  - Child, Preschool
MH  - Cyclin-Dependent Kinase Inhibitor p27
MH  - DNA-Binding Proteins/genetics
MH  - Female
MH  - *Gene Deletion
MH  - HL-60 Cells
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Male
MH  - Microtubule-Associated Proteins/*genetics
MH  - Molecular Sequence Data
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics
MH  - Proto-Oncogene Proteins c-ets
MH  - *Repressor Proteins
MH  - Restriction Mapping
MH  - Transcription Factors/genetics
MH  - *Tumor Suppressor Proteins
MH  - ETS Translocation Variant 6 Protein
PMC - PMC1508076
EDAT- 2000/08/10 11:00
MHDA- 2000/08/19 11:00
PMCR- 1999/08/01
CRDT- 2000/08/10 11:00
PHST- 2000/08/10 11:00 [pubmed]
PHST- 2000/08/19 11:00 [medline]
PHST- 2000/08/10 11:00 [entrez]
PHST- 1999/08/01 00:00 [pmc-release]
AID - 0033a [pii]
AID - 10.1038/sj.neo.7900033 [doi]
PST - ppublish
SO  - Neoplasia. 1999 Aug;1(3):253-61. doi: 10.1038/sj.neo.7900033.