| Relationship of p15 and p16 gene alterations to elevated dihydrofolate reductase in childhood acute lymphoblastic leukaemia. | |
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MedLine Citation:
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PMID: 11380466 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: British journal of haematology Volume: 113 ISSN: 0007-1048 ISO Abbreviation: Br. J. Haematol. Publication Date: 2001 Jun |
Date Detail:
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Created Date: 2001-05-30 Completed Date: 2001-07-05 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0372544 Medline TA: Br J Haematol Country: England |
Other Details:
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Languages: eng Pagination: 746-56 Citation Subset: IM |
Affiliation:
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Experimental and Clinical Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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CA77641/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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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