Variable expression of p16 protein in patients with acute myeloid leukemia without gross rearrangements at the DNA level

A. Rahman A. Jamal, N. S B Thomas, R. E. Gale, D. C. Linch

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The p16 protein is an inhibitor of cyclin-dependent kinases (cdk) 4 and 6. Both cdk4 and cdk6 phosphorylate the retinoblastoma protein (pRb) and are thought to be required for cell proliferation. Mutations and homozygous deletions in the p16 gene have been found in a number of cell lines but the incidence of abnormalities in primary tumours is controversial. We have studied the p16 gene in 76 cases of acute myeloid leukemia (AML) and 18 hematologically normal controls by quantitative Southern blotting. No deletions or rearrangements were detected. Twenty-five cases also showed no abnormal band patterns by RT-PCR-SSCP analysis of the coding sequence. We analyzed 60 AML samples for p16 protein expression by Western blot analysis. A reduced level of p16 was observed in six cases, however none of them showed methylation of the 5'-CPG island. Over-expression of p16 protein was detected in six cases. Studies in cell lines have suggested a feedback loop between p16 and pRb with a futile overproduction of p16 protein in cells containing abnormal pRb. In accordance with these findings, four of the AML cases with high levels of p16 had abnormal pRb (two alteration in band size, two absent). From our data we suggest that gross abnormalities in the p16 gene are rare in AML, but that p16 levels are variable and high levels are associated with pRb abnormalities in a subset of cases.

Original languageEnglish
Pages (from-to)629-636
Number of pages8
JournalLeukemia
Volume10
Issue number4
Publication statusPublished - Apr 1996
Externally publishedYes

Fingerprint

Retinoblastoma Protein
Gene Rearrangement
Acute Myeloid Leukemia
p16 Genes
Proteins
Cyclin-Dependent Kinase 6
Single-Stranded Conformational Polymorphism
Cell Line
Sequence Deletion
Southern Blotting
Islands
Methylation
Sequence Analysis
Western Blotting
Cell Proliferation
Polymerase Chain Reaction
Incidence
Neoplasms

Keywords

  • Acute myeloid leukemia
  • p16

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Variable expression of p16 protein in patients with acute myeloid leukemia without gross rearrangements at the DNA level. / A. Jamal, A. Rahman; Thomas, N. S B; Gale, R. E.; Linch, D. C.

In: Leukemia, Vol. 10, No. 4, 04.1996, p. 629-636.

Research output: Contribution to journalArticle

@article{d412feda593f424283be059edcd23443,
title = "Variable expression of p16 protein in patients with acute myeloid leukemia without gross rearrangements at the DNA level",
abstract = "The p16 protein is an inhibitor of cyclin-dependent kinases (cdk) 4 and 6. Both cdk4 and cdk6 phosphorylate the retinoblastoma protein (pRb) and are thought to be required for cell proliferation. Mutations and homozygous deletions in the p16 gene have been found in a number of cell lines but the incidence of abnormalities in primary tumours is controversial. We have studied the p16 gene in 76 cases of acute myeloid leukemia (AML) and 18 hematologically normal controls by quantitative Southern blotting. No deletions or rearrangements were detected. Twenty-five cases also showed no abnormal band patterns by RT-PCR-SSCP analysis of the coding sequence. We analyzed 60 AML samples for p16 protein expression by Western blot analysis. A reduced level of p16 was observed in six cases, however none of them showed methylation of the 5'-CPG island. Over-expression of p16 protein was detected in six cases. Studies in cell lines have suggested a feedback loop between p16 and pRb with a futile overproduction of p16 protein in cells containing abnormal pRb. In accordance with these findings, four of the AML cases with high levels of p16 had abnormal pRb (two alteration in band size, two absent). From our data we suggest that gross abnormalities in the p16 gene are rare in AML, but that p16 levels are variable and high levels are associated with pRb abnormalities in a subset of cases.",
keywords = "Acute myeloid leukemia, p16",
author = "{A. Jamal}, {A. Rahman} and Thomas, {N. S B} and Gale, {R. E.} and Linch, {D. C.}",
year = "1996",
month = "4",
language = "English",
volume = "10",
pages = "629--636",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Variable expression of p16 protein in patients with acute myeloid leukemia without gross rearrangements at the DNA level

AU - A. Jamal, A. Rahman

AU - Thomas, N. S B

AU - Gale, R. E.

AU - Linch, D. C.

PY - 1996/4

Y1 - 1996/4

N2 - The p16 protein is an inhibitor of cyclin-dependent kinases (cdk) 4 and 6. Both cdk4 and cdk6 phosphorylate the retinoblastoma protein (pRb) and are thought to be required for cell proliferation. Mutations and homozygous deletions in the p16 gene have been found in a number of cell lines but the incidence of abnormalities in primary tumours is controversial. We have studied the p16 gene in 76 cases of acute myeloid leukemia (AML) and 18 hematologically normal controls by quantitative Southern blotting. No deletions or rearrangements were detected. Twenty-five cases also showed no abnormal band patterns by RT-PCR-SSCP analysis of the coding sequence. We analyzed 60 AML samples for p16 protein expression by Western blot analysis. A reduced level of p16 was observed in six cases, however none of them showed methylation of the 5'-CPG island. Over-expression of p16 protein was detected in six cases. Studies in cell lines have suggested a feedback loop between p16 and pRb with a futile overproduction of p16 protein in cells containing abnormal pRb. In accordance with these findings, four of the AML cases with high levels of p16 had abnormal pRb (two alteration in band size, two absent). From our data we suggest that gross abnormalities in the p16 gene are rare in AML, but that p16 levels are variable and high levels are associated with pRb abnormalities in a subset of cases.

AB - The p16 protein is an inhibitor of cyclin-dependent kinases (cdk) 4 and 6. Both cdk4 and cdk6 phosphorylate the retinoblastoma protein (pRb) and are thought to be required for cell proliferation. Mutations and homozygous deletions in the p16 gene have been found in a number of cell lines but the incidence of abnormalities in primary tumours is controversial. We have studied the p16 gene in 76 cases of acute myeloid leukemia (AML) and 18 hematologically normal controls by quantitative Southern blotting. No deletions or rearrangements were detected. Twenty-five cases also showed no abnormal band patterns by RT-PCR-SSCP analysis of the coding sequence. We analyzed 60 AML samples for p16 protein expression by Western blot analysis. A reduced level of p16 was observed in six cases, however none of them showed methylation of the 5'-CPG island. Over-expression of p16 protein was detected in six cases. Studies in cell lines have suggested a feedback loop between p16 and pRb with a futile overproduction of p16 protein in cells containing abnormal pRb. In accordance with these findings, four of the AML cases with high levels of p16 had abnormal pRb (two alteration in band size, two absent). From our data we suggest that gross abnormalities in the p16 gene are rare in AML, but that p16 levels are variable and high levels are associated with pRb abnormalities in a subset of cases.

KW - Acute myeloid leukemia

KW - p16

UR - http://www.scopus.com/inward/record.url?scp=0029911750&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029911750&partnerID=8YFLogxK

M3 - Article

C2 - 8618439

AN - SCOPUS:0029911750

VL - 10

SP - 629

EP - 636

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 4

ER -