Vincristine activates c-Jun N-terminal kinase in chronic lymphocytic leukaemia in vivo

Darcy J P Bates, Lionel D. Lewis, Alan Eastman, Alexey Danilov

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Aims The authors' aim was to conduct a proof-of-principle study to test whether c-Jun N-terminal kinase (JNK) phosphorylation and Noxa induction occur in peripheral blood chronic lymphocytic leukaemia (CLL) cells in patients receiving a vincristine infusion. Methods Patients with CLL received 2 mg vincristine by a 5-min intravenous infusion. Blood samples were collected at baseline and up to 6 h after the vincristine infusion, and assayed for JNK activation, Noxa induction and vincristine plasma concentrations. Results Ex vivo treated peripheral CLL cells activated JNK in response to 10-100 nM vincristine in 6 h. Noxa protein expression, while variable, was also observed over this time frame. In CLL patients, vincristine infusion led to rapid (

Original languageEnglish (US)
Pages (from-to)493-501
Number of pages9
JournalBritish Journal of Clinical Pharmacology
Volume80
Issue number3
DOIs
StatePublished - Sep 1 2015
Externally publishedYes

Fingerprint

JNK Mitogen-Activated Protein Kinases
Vincristine
B-Cell Chronic Lymphocytic Leukemia
Noxae
Phosphotransferases
Intravenous Infusions
Phosphorylation
Proteins

Keywords

  • apoptosis
  • c-Jun N-terminal kinase
  • chronic lymphocytic leukaemia
  • Noxa
  • vincristine

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Vincristine activates c-Jun N-terminal kinase in chronic lymphocytic leukaemia in vivo. / Bates, Darcy J P; Lewis, Lionel D.; Eastman, Alan; Danilov, Alexey.

In: British Journal of Clinical Pharmacology, Vol. 80, No. 3, 01.09.2015, p. 493-501.

Research output: Contribution to journalArticle

Bates, Darcy J P ; Lewis, Lionel D. ; Eastman, Alan ; Danilov, Alexey. / Vincristine activates c-Jun N-terminal kinase in chronic lymphocytic leukaemia in vivo. In: British Journal of Clinical Pharmacology. 2015 ; Vol. 80, No. 3. pp. 493-501.
@article{096b1e3156b641f39fe5d8555ac149ab,
title = "Vincristine activates c-Jun N-terminal kinase in chronic lymphocytic leukaemia in vivo",
abstract = "Aims The authors' aim was to conduct a proof-of-principle study to test whether c-Jun N-terminal kinase (JNK) phosphorylation and Noxa induction occur in peripheral blood chronic lymphocytic leukaemia (CLL) cells in patients receiving a vincristine infusion. Methods Patients with CLL received 2 mg vincristine by a 5-min intravenous infusion. Blood samples were collected at baseline and up to 6 h after the vincristine infusion, and assayed for JNK activation, Noxa induction and vincristine plasma concentrations. Results Ex vivo treated peripheral CLL cells activated JNK in response to 10-100 nM vincristine in 6 h. Noxa protein expression, while variable, was also observed over this time frame. In CLL patients, vincristine infusion led to rapid (",
keywords = "apoptosis, c-Jun N-terminal kinase, chronic lymphocytic leukaemia, Noxa, vincristine",
author = "Bates, {Darcy J P} and Lewis, {Lionel D.} and Alan Eastman and Alexey Danilov",
year = "2015",
month = "9",
day = "1",
doi = "10.1111/bcp.12624",
language = "English (US)",
volume = "80",
pages = "493--501",
journal = "British Journal of Clinical Pharmacology",
issn = "0306-5251",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Vincristine activates c-Jun N-terminal kinase in chronic lymphocytic leukaemia in vivo

AU - Bates, Darcy J P

AU - Lewis, Lionel D.

AU - Eastman, Alan

AU - Danilov, Alexey

PY - 2015/9/1

Y1 - 2015/9/1

N2 - Aims The authors' aim was to conduct a proof-of-principle study to test whether c-Jun N-terminal kinase (JNK) phosphorylation and Noxa induction occur in peripheral blood chronic lymphocytic leukaemia (CLL) cells in patients receiving a vincristine infusion. Methods Patients with CLL received 2 mg vincristine by a 5-min intravenous infusion. Blood samples were collected at baseline and up to 6 h after the vincristine infusion, and assayed for JNK activation, Noxa induction and vincristine plasma concentrations. Results Ex vivo treated peripheral CLL cells activated JNK in response to 10-100 nM vincristine in 6 h. Noxa protein expression, while variable, was also observed over this time frame. In CLL patients, vincristine infusion led to rapid (

AB - Aims The authors' aim was to conduct a proof-of-principle study to test whether c-Jun N-terminal kinase (JNK) phosphorylation and Noxa induction occur in peripheral blood chronic lymphocytic leukaemia (CLL) cells in patients receiving a vincristine infusion. Methods Patients with CLL received 2 mg vincristine by a 5-min intravenous infusion. Blood samples were collected at baseline and up to 6 h after the vincristine infusion, and assayed for JNK activation, Noxa induction and vincristine plasma concentrations. Results Ex vivo treated peripheral CLL cells activated JNK in response to 10-100 nM vincristine in 6 h. Noxa protein expression, while variable, was also observed over this time frame. In CLL patients, vincristine infusion led to rapid (

KW - apoptosis

KW - c-Jun N-terminal kinase

KW - chronic lymphocytic leukaemia

KW - Noxa

KW - vincristine

UR - http://www.scopus.com/inward/record.url?scp=84940449337&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84940449337&partnerID=8YFLogxK

U2 - 10.1111/bcp.12624

DO - 10.1111/bcp.12624

M3 - Article

VL - 80

SP - 493

EP - 501

JO - British Journal of Clinical Pharmacology

JF - British Journal of Clinical Pharmacology

SN - 0306-5251

IS - 3

ER -