NDLI: MCL-1 but not BCL-XL is critical for the development and sustained expansion of thymic lymphoma in p53-deficient mice

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MCL-1 but not BCL-XL is critical for the development and sustained expansion of thymic lymphoma in p53-deficient mice

Content Provider	Scilit
Author	Grabow, Stephanie Delbridge, Alex R. D. Valente, Liz J. Strasser, Andreas
Copyright Year	2014
Description	Apoptosis plays a role in normal lymphopoiesis and lymphoid malignancies. Pro-survival MCL-1 is essential for survival of T cell progenitors, BCL-XL for immature thymocytes and BCL-2 for mature T cells. Conversely, only little is known about the regulators that are required for the survival of T cell lymphomas. We used constitutive and conditionally gene-targeted mice to investigate which pro-survival BCL-2 family member is required for the sustained survival of thymic lymphomas initiated by loss of p53. Constitutive loss of a single Mcl-1 allele delayed tumor onset and lymphomas emerging in $p53^{-/-}$ mice in which Mcl-1 could be conditionally deleted had been selected for retention of MCL-1 expression. In contrast, complete loss of BCL-XL had no impact on lymphoma development in $p53^{-/-}$ mice. These results demonstrate that thymic lymphomas elicited by loss of p53 must arise from cancer initiating cells that require MCL-1 for their survival. Acute deletion of both Mcl-1 alleles abrogated the expansion of $p53^{-/-}$ lymphomas in mice whereas inducible loss of BCL-XL had little impact. This reveals that MCL-1 is essential for the sustained survival of these malignant cells and suggests that targeting MCL-1 may be an attractive strategy for the treatment of T cell lymphoma.
Related Links	https://ashpublications.org/blood/article-pdf/124/26/3939/1465875/3939.pdf
Ending Page	3946
Page Count	8
Starting Page	3939
DOI	10.1182/blood-2014-09-601567
Journal	Blood
Issue Number	26
Volume Number	124
Language	English
Publisher	American Society of Hematology
Publisher Date	2014-12-18
Access Restriction	Open
Subject Keyword	Hematology Research and Experimental Medicine Survival Apoptosis Lymphomas Bcl Xl P53 Expansion Mcl Treatment Journal: Blood (Vol- 2017, Issue- 26)
Content Type	Text
Resource Type	Article

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