Loss of PKR Activity in Chronic Lymphocytic Leukemia

Hii, S. I., Hardy, L., Crough, T., Payne, E. J., Grimmett, K., Gill, D. and McMillan, N. A. J. (2004) Loss of PKR Activity in Chronic Lymphocytic Leukemia. International Journal of Cancer, 109 3: 329-335. doi:10.1002/ijc.11714


Author Hii, S. I.
Hardy, L.
Crough, T.
Payne, E. J.
Grimmett, K.
Gill, D.
McMillan, N. A. J.
Title Loss of PKR Activity in Chronic Lymphocytic Leukemia
Journal name International Journal of Cancer   Check publisher's open access policy
ISSN 0020-7136
Publication date 2004
Sub-type Article (original research)
DOI 10.1002/ijc.11714
Volume 109
Issue 3
Start page 329
End page 335
Total pages 7
Editor H. zur Hausen (Editor-in-Chief)
Place of publication United States
Publisher John Wiley & Sons, Inc.
Collection year 2004
Language eng
Subject C1
320402 Medical Virology
730108 Cancer and related disorders
Abstract There are a number of observations that suggest the dsRNA-activated protein kinase, PKR, may play an active role in formation and maintenance of leukemia, including nonrandom chromosomal deletions in acute leukemia as well as truncations and deletions of the PKR gene in some leukemia cell lines. However, there is little direct evidence from patient material that this is so. Here we show that full-length PKR is present but not active in 21 of 28 patient samples from B-cell chronic lymphocytic leukemia (B-CLL). PKR from these patients was unable to auto-activate or phosphorylate substrates but was able to bind dsRNA. Furthermore, the lack of PKR activation was not due to differing levels of the PKR activator, PACT nor of the PKR inhibitor, p58(IPK). We compared PKR status with clinical parameters and disease staging. No differences were found between the 2 groups in terms of staging (modified Rai or Binet), age, CD38 status, p53 status, 11q23 deletion status or CEP12 deletion status. However, there was a significant correlation between deletion in 13q14.3 and lack of PKR activity. We show that B-CLL cells appear to contain a soluble inhibitor of PKR, as lysates from cells lacking PKR activity were able to inhibit exogenous PKR in mixing experiments. Finally, we show suppression of PKR activity was still present following ultrafilitration through a 10,000 Da cutoff filter but was lost upon extraction with phenol/chloroform or by high salt washing. This data suggests loss of PKR activity may contribute to the formation and/or maintenance of CLL. (C) 2004 Wiley-Liss, Inc.
Keyword Pkr
B-cll
Interferon
Dsrna
P58(ipk)
Pact
Dependent Protein-kinase
Tumor-suppressor Gene
B-cells
Malignant-transformation
Chromosomal Assignment
Induced Apoptosis
Rna
Death
Translation
Inhibition
Oncology
Q-Index Code C1
Additional Notes Published Online: 9 Jan 2004

 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 28 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 32 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 15 Aug 2007, 04:10:27 EST