Targeting the RAF/MEK/ERK, PI3K/AKT and P53 pathways in hematopoietic drug resistance

James A. McCubrey, Linda S. Steelman, Richard A. Franklin, Steven L. Abrams, William H. Chappell, Ellis W T Wong, Brian D. Lehmann, David M. Terrian, Jorg Basecke, Franca Stivala, Massimo Libra, Camilla Evangelisti, Alberto M. Martelli

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

We have presented data which documents the importance of the Raf>MEK>ERK and PI3K>Akt pathways in the development of drug resistance in hematopoietic cells. Further understanding of how these pathways interact and induce drug resistance could result in the identification of novel approaches to treat drug resistance in leukemia. Furthermore, p53 played a role in drug resistance in these cells as introduction of a DN-p53 construct increased the resistance of the cells to chemotherapeutic drugs. The drug-sensitive and drug-resistant FL/ΔAkt:ER+ΔRaf-1:AR cells will allow us the ability to determine not only which downstream components are induced by either Raf>MEK>ERK or PI3K>Akt that are necessary for proliferation and prevention of apoptosis, but also which components are important in drug resistance and how these two pathways can interact to influence drug resistance.

Original languageEnglish
Pages (from-to)64-103
Number of pages40
JournalAdvances in Enzyme Regulation
Volume47
DOIs
Publication statusPublished - 2007

Fingerprint

Mitogen-Activated Protein Kinase Kinases
Phosphatidylinositol 3-Kinases
Drug Resistance
Pharmaceutical Preparations
Leukemia
Apoptosis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

McCubrey, J. A., Steelman, L. S., Franklin, R. A., Abrams, S. L., Chappell, W. H., Wong, E. W. T., ... Martelli, A. M. (2007). Targeting the RAF/MEK/ERK, PI3K/AKT and P53 pathways in hematopoietic drug resistance. Advances in Enzyme Regulation, 47, 64-103. https://doi.org/10.1016/j.advenzreg.2006.12.013

Targeting the RAF/MEK/ERK, PI3K/AKT and P53 pathways in hematopoietic drug resistance. / McCubrey, James A.; Steelman, Linda S.; Franklin, Richard A.; Abrams, Steven L.; Chappell, William H.; Wong, Ellis W T; Lehmann, Brian D.; Terrian, David M.; Basecke, Jorg; Stivala, Franca; Libra, Massimo; Evangelisti, Camilla; Martelli, Alberto M.

In: Advances in Enzyme Regulation, Vol. 47, 2007, p. 64-103.

Research output: Contribution to journalArticle

McCubrey, JA, Steelman, LS, Franklin, RA, Abrams, SL, Chappell, WH, Wong, EWT, Lehmann, BD, Terrian, DM, Basecke, J, Stivala, F, Libra, M, Evangelisti, C & Martelli, AM 2007, 'Targeting the RAF/MEK/ERK, PI3K/AKT and P53 pathways in hematopoietic drug resistance', Advances in Enzyme Regulation, vol. 47, pp. 64-103. https://doi.org/10.1016/j.advenzreg.2006.12.013
McCubrey, James A. ; Steelman, Linda S. ; Franklin, Richard A. ; Abrams, Steven L. ; Chappell, William H. ; Wong, Ellis W T ; Lehmann, Brian D. ; Terrian, David M. ; Basecke, Jorg ; Stivala, Franca ; Libra, Massimo ; Evangelisti, Camilla ; Martelli, Alberto M. / Targeting the RAF/MEK/ERK, PI3K/AKT and P53 pathways in hematopoietic drug resistance. In: Advances in Enzyme Regulation. 2007 ; Vol. 47. pp. 64-103.
@article{25dd77dd49494849b6b62700e551d754,
title = "Targeting the RAF/MEK/ERK, PI3K/AKT and P53 pathways in hematopoietic drug resistance",
abstract = "We have presented data which documents the importance of the Raf>MEK>ERK and PI3K>Akt pathways in the development of drug resistance in hematopoietic cells. Further understanding of how these pathways interact and induce drug resistance could result in the identification of novel approaches to treat drug resistance in leukemia. Furthermore, p53 played a role in drug resistance in these cells as introduction of a DN-p53 construct increased the resistance of the cells to chemotherapeutic drugs. The drug-sensitive and drug-resistant FL/ΔAkt:ER+ΔRaf-1:AR cells will allow us the ability to determine not only which downstream components are induced by either Raf>MEK>ERK or PI3K>Akt that are necessary for proliferation and prevention of apoptosis, but also which components are important in drug resistance and how these two pathways can interact to influence drug resistance.",
author = "McCubrey, {James A.} and Steelman, {Linda S.} and Franklin, {Richard A.} and Abrams, {Steven L.} and Chappell, {William H.} and Wong, {Ellis W T} and Lehmann, {Brian D.} and Terrian, {David M.} and Jorg Basecke and Franca Stivala and Massimo Libra and Camilla Evangelisti and Martelli, {Alberto M.}",
year = "2007",
doi = "10.1016/j.advenzreg.2006.12.013",
language = "English",
volume = "47",
pages = "64--103",
journal = "Advances in Enzyme Regulation",
issn = "0065-2571",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Targeting the RAF/MEK/ERK, PI3K/AKT and P53 pathways in hematopoietic drug resistance

AU - McCubrey, James A.

AU - Steelman, Linda S.

AU - Franklin, Richard A.

AU - Abrams, Steven L.

AU - Chappell, William H.

AU - Wong, Ellis W T

AU - Lehmann, Brian D.

AU - Terrian, David M.

AU - Basecke, Jorg

AU - Stivala, Franca

AU - Libra, Massimo

AU - Evangelisti, Camilla

AU - Martelli, Alberto M.

PY - 2007

Y1 - 2007

N2 - We have presented data which documents the importance of the Raf>MEK>ERK and PI3K>Akt pathways in the development of drug resistance in hematopoietic cells. Further understanding of how these pathways interact and induce drug resistance could result in the identification of novel approaches to treat drug resistance in leukemia. Furthermore, p53 played a role in drug resistance in these cells as introduction of a DN-p53 construct increased the resistance of the cells to chemotherapeutic drugs. The drug-sensitive and drug-resistant FL/ΔAkt:ER+ΔRaf-1:AR cells will allow us the ability to determine not only which downstream components are induced by either Raf>MEK>ERK or PI3K>Akt that are necessary for proliferation and prevention of apoptosis, but also which components are important in drug resistance and how these two pathways can interact to influence drug resistance.

AB - We have presented data which documents the importance of the Raf>MEK>ERK and PI3K>Akt pathways in the development of drug resistance in hematopoietic cells. Further understanding of how these pathways interact and induce drug resistance could result in the identification of novel approaches to treat drug resistance in leukemia. Furthermore, p53 played a role in drug resistance in these cells as introduction of a DN-p53 construct increased the resistance of the cells to chemotherapeutic drugs. The drug-sensitive and drug-resistant FL/ΔAkt:ER+ΔRaf-1:AR cells will allow us the ability to determine not only which downstream components are induced by either Raf>MEK>ERK or PI3K>Akt that are necessary for proliferation and prevention of apoptosis, but also which components are important in drug resistance and how these two pathways can interact to influence drug resistance.

UR - http://www.scopus.com/inward/record.url?scp=34548124684&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548124684&partnerID=8YFLogxK

U2 - 10.1016/j.advenzreg.2006.12.013

DO - 10.1016/j.advenzreg.2006.12.013

M3 - Article

C2 - 17382374

AN - SCOPUS:34548124684

VL - 47

SP - 64

EP - 103

JO - Advances in Enzyme Regulation

JF - Advances in Enzyme Regulation

SN - 0065-2571

ER -