Document Detail


Relationship of p15 and p16 gene alterations to elevated dihydrofolate reductase in childhood acute lymphoblastic leukaemia.
MedLine Citation:
PMID:  11380466     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The downstream effects of p15 and p16 gene deletions and loss of transcripts on dihydrofolate reductase (DHFR) were examined in 63 B-precursor (BP) acute lymphoblastic leukaemia (ALL) samples. p15 and/or p16 gene deletions were seen in 6% and 8%, respectively, of BP-ALL samples; however, losses of p15 and/or p16 transcripts were seen in 26 out of 63 (41%) samples. Loss of p15 transcripts (36.5%) exceeded that for p16 (17.5%). For the 26 BP-ALLs that lacked p15 and/or p16 transcripts, only six (23%) exhibited low levels of DHFR by flow cytometry assay with Pt430, a fluorescent anti-folate. Conversely, 18 out of 37 (49%) BP-ALL samples with intact p15 and/or p16 genes and transcripts showed low levels of DHFR (P = 0.04). In p15- and p16-null K562 cells transfected with a tetracycline-inducible p15 cDNA construct, induction of p15 transcripts and protein was accompanied by decreased growth rates, decreased S-phase fraction, decreased retinoblastoma protein phosphorylation, and markedly reduced levels of DHFR transcripts and protein. Collectively, our results suggest that losses of p15 and/or p16 gene expression result in elevated levels of DHFR in BP-ALL in children. However, additional downstream factors undoubtedly also contribute to elevated levels of this enzyme target.
Authors:
S J Shah; J W Taub; T L Witt; B H Pollock; B C Ding; D S Moore; M Amylon; J Pullen; Y Ravindranath; L H Matherly
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  British journal of haematology     Volume:  113     ISSN:  0007-1048     ISO Abbreviation:  Br. J. Haematol.     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-05-30     Completed Date:  2001-07-05     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0372544     Medline TA:  Br J Haematol     Country:  England    
Other Details:
Languages:  eng     Pagination:  746-56     Citation Subset:  IM    
Affiliation:
Experimental and Clinical Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan, USA.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Blotting, Southern
Burkitt Lymphoma / enzymology,  genetics*
Case-Control Studies
Cell Cycle
Cell Cycle Proteins*
Child
Child, Preschool
Confidence Intervals
Cyclin-Dependent Kinase Inhibitor p15
Dose-Response Relationship, Drug
Doxycycline / pharmacology
Female
Flow Cytometry
Gene Deletion*
Gene Expression / drug effects
Genes, p16*
Humans
Infant
K562 Cells
Logistic Models
Male
Odds Ratio
RNA, Messenger / analysis
Reverse Transcriptase Polymerase Chain Reaction
Tetrahydrofolate Dehydrogenase / genetics*
Transcription Factors / genetics*
Tumor Suppressor Proteins*
Grant Support
ID/Acronym/Agency:
CA77641/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/CDKN2B protein, human; 0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p15; 0/RNA, Messenger; 0/Transcription Factors; 0/Tumor Suppressor Proteins; 564-25-0/Doxycycline; EC 1.5.1.3/Tetrahydrofolate Dehydrogenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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