Src, Akt, NF-κB, BCL-2 and c-IAP1 may be involved in an anti-apoptotic effect in patients with BCR-ABL positive and BCR-ABL negative acute lymphoblastic leukemia

José E Vázquez-Franco; Elba Reyes-Maldonado; Jorge Vela-Ojeda; Maria L Domínguez-López; Ruth A Lezama

doi:10.1016/j.leukres.2012.03.020

Src, Akt, NF-κB, BCL-2 and c-IAP1 may be involved in an anti-apoptotic effect in patients with BCR-ABL positive and BCR-ABL negative acute lymphoblastic leukemia

Leuk Res. 2012 Jul;36(7):862-7. doi: 10.1016/j.leukres.2012.03.020. Epub 2012 May 14.

Authors

José E Vázquez-Franco¹, Elba Reyes-Maldonado, Jorge Vela-Ojeda, Maria L Domínguez-López, Ruth A Lezama

Affiliation

¹ Department of morphology, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, México city, Mexico.

PMID: 22591684
DOI: 10.1016/j.leukres.2012.03.020

Abstract

BCR-ABL kinase has been observed to be potentially related to leukemic cell development. Adult patients with acute lymphoblastic leukemia (ALL) were evaluated to determine whether presence/absence of BCR-ABL induced differences in activation of Src, PI3K/Akt and NF-κB or in the expression of anti-apoptotic proteins such as BCL-2 and c-IAP1. BCR-ABL positive patients showed a significantly higher activation of Src and Akt compared with BCR-ABL negative patients and healthy donors. BCR-ABL negative patients also showed a significant activation of Src and low levels of Akt activation compared with healthy donors. Both patient groups had increased NF-κB activation and overexpression of BCL-2 and c-IAP1. This is the first study to evaluate concurrently in ALL patients presence/absence of BCR-ABL in relation to activation of Src, Akt and NF-κB and the expression of anti-apoptotic proteins. Results suggest that these proteins may be involved in an anti-apoptotic signaling pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Apoptosis / genetics*
Apoptosis Regulatory Proteins / genetics
Apoptosis Regulatory Proteins / metabolism
Apoptosis Regulatory Proteins / physiology
Bone Marrow Examination
Case-Control Studies
Female
Fusion Proteins, bcr-abl / genetics
Fusion Proteins, bcr-abl / metabolism*
Gene Expression Regulation, Leukemic
Humans
Inhibitor of Apoptosis Proteins / genetics
Inhibitor of Apoptosis Proteins / metabolism
Inhibitor of Apoptosis Proteins / physiology*
Male
NF-kappa B / genetics
NF-kappa B / metabolism
NF-kappa B / physiology*
Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
Proto-Oncogene Proteins c-akt / genetics
Proto-Oncogene Proteins c-akt / metabolism
Proto-Oncogene Proteins c-akt / physiology*
Proto-Oncogene Proteins c-bcl-2 / genetics
Proto-Oncogene Proteins c-bcl-2 / metabolism
Proto-Oncogene Proteins c-bcl-2 / physiology*
Proto-Oncogene Proteins pp60(c-src) / genetics
Proto-Oncogene Proteins pp60(c-src) / metabolism
Proto-Oncogene Proteins pp60(c-src) / physiology*
Signal Transduction / genetics

Substances

Apoptosis Regulatory Proteins
Inhibitor of Apoptosis Proteins
NF-kappa B
Proto-Oncogene Proteins c-bcl-2
Fusion Proteins, bcr-abl
Proto-Oncogene Proteins pp60(c-src)
Proto-Oncogene Proteins c-akt