Antiapoptotic BCL-2 is required for maintenance of a model leukemia

Cancer Cell
Anthony LetaiStanley J Korsmeyer

Abstract

Resistance to apoptosis, often achieved by the overexpression of antiapoptotic proteins, is common and perhaps required in the genesis of cancer. However, it remains uncertain whether apoptotic defects are essential for tumor maintenance. To test this, we generated mice expressing a conditional BCL-2 gene and constitutive c-myc that develop lymphoblastic leukemia. Eliminating BCL-2 yielded rapid loss of leukemic cells and significantly prolonged survival, formally validating BCL-2 as a rational target for cancer therapy. Loss of this single molecule resulted in cell death, despite or perhaps attributable to the presence of other oncogenic events. This suggests a generalizable model in which aberrations inherent to cancer generate tonic death signals that would otherwise kill the cell if not opposed by a requisite apoptotic defect(s).

References

Nov 21, 1998·Leukemia·N HaradaH Mitsuya
Sep 17, 1999·Molecular Cell·D W Felsher, J M Bishop
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Jun 22, 2000·Proceedings of the National Academy of Sciences of the United States of America·J L WangZ Huang
Jun 27, 2000·Archives of Dermatological Research·U LeiterG Krähn
Feb 26, 2003·Genes & Development·Edward J GuntherLewis A Chodosh
Apr 3, 2003·Nature Reviews. Cancer·Clemens A Schmitt
Jan 28, 2004·Cell·Nika N Danial, Stanley J Korsmeyer

❮ Previous
Next ❯

Citations

Apr 25, 2007·Apoptosis : an International Journal on Programmed Cell Death·Brian LeberDavid W Andrews
Jun 22, 2010·Apoptosis : an International Journal on Programmed Cell Death·Joanna SkommerSubhadip Raychaudhuri
Sep 9, 2010·Expert Reviews in Molecular Medicine·Brian LeberDavid W Andrews
Mar 19, 2011·Cell Death and Differentiation·P N Kelly, A Strasser
May 20, 2005·Nature·Tilman OltersdorfSaul H Rosenberg
Jul 31, 2009·Oncogene·T Ni Chonghaile, A Letai
Jun 10, 2006·Cell Death and Differentiation·L D Walensky
Aug 8, 2006·Oncogene·M FontenayE Solary
Mar 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Katrina PodsypaninaHarold E Varmus
Nov 14, 2008·Proceedings of the National Academy of Sciences of the United States of America·Kylie D MasonAndrew W Roberts
Jan 5, 2011·The Journal of Biological Chemistry·Peter E CzabotarPeter M Colman
Mar 20, 2010·Carcinogenesis·Inés González-HerreroIsidro Sánchez-García
May 17, 2012·Cancer Research·Kelly C GoldsmithMichael D Hogarty
Jun 21, 2008·Molecular Cancer Therapeutics·Dayong ZhaiJohn C Reed
Oct 4, 2005·The Journal of Clinical Investigation·Anthony Letai
Oct 4, 2005·The Journal of Clinical Investigation·Lisa Bouchier-HayesDonald D Newmeyer
Jan 4, 2007·The Journal of Clinical Investigation·Victoria Del Gaizo MooreAnthony Letai
Jun 5, 2008·The Journal of Clinical Investigation·Avi Ashkenazi, Roy S Herbst
May 25, 2012·The Journal of Clinical Investigation·James L LaBelleLoren D Walensky
Dec 7, 2007·Blood·Victoria Del Gaizo MooreAnthony Letai
May 24, 2011·World Journal of Clinical Oncology·Subhadip Raychaudhuri
Mar 5, 2010·EMBO Molecular Medicine·Andrea HoelblVeronika Sexl
Aug 19, 2014·Mitochondrion·Giovanni SorrentinoGiannino Del Sal
May 31, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mohammad Aminur RahmanDong M Shin
Dec 2, 2009·The Journal of Cell Biology·Joslyn K BrunelleAnthony Letai
Dec 23, 2015·Cancer Investigation·Sichuang TanWeilin Zhang
Mar 19, 2013·Journal of Healthcare Engineering·Subhadip Raychaudhuri, Somkanya C Das
Jul 24, 2015·Clinical and Experimental Immunology·R NewmanM Turner
Dec 3, 2014·Journal of Molecular Biology·Sanjib DuttaAmy E Keating
Dec 13, 2006·Experimental Hematology·Clara CampàsJoan Gil

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

B-Cell Leukemia (Keystone)

B-cell leukemia includes various types of lymphoid leukemia that affect B cells. Here is the latest research on B-cell leukemia.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis