The phosphodiesterase PDE4B limits cAMP-associated PI3K/AKT-dependent apoptosis in diffuse large B-cell lymphoma.

Blood
Peter G SmithRicardo C T Aguiar

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a common and often fatal malignancy. Advances in the treatment of this disease will require the identification of novel therapeutic targets. We previously defined an expression signature of outcome in DLBCL and found that the phosphodiesterase PDE4B was overexpressed in fatal/refractory tumors. Phosphodiesterase 4B (PDE4B) inactivates the second messenger cyclic adenosine 3',5' monophosphate (cAMP) and abrogates its inhibitory effects in B lymphocytes. Hence, DLBCLs that express high PDE4B levels may be resistant to cAMP-induced apoptosis, contributing to their less favorable outcome. Herein, we confirmed the risk-related expression of PDE4B in an independent series of primary DLBCLs and defined the enzyme's role in modulating cAMP-induced apoptosis in parental DLBCL cell lines or those reconstituted with wild-type or mutant PDE4B. The cAMP-mediated apoptosis of DLBCLs was largely independent of the previously described cAMP effectors, protein kinase A (PKA) and exchange protein directly activated by cAMP (EPAC), but associated with inhibition of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. The central role of AKT in this process was confirmed by expressing constitutively active...Continue Reading

References

Mar 14, 2000·Current Opinion in Cell Biology·S H Soderling, J A Beavo
Mar 30, 2001·The Journal of Biological Chemistry·S KimJ Chung
Jul 27, 2001·Current Opinion in Chemical Biology·Z HuangA Robichaud
Aug 8, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·K J StaplesR Newton
May 16, 2002·Chest·Graham Sturton, Mary Fitzgerald
Jun 4, 2002·Current Opinion in Hematology·R Eric Davis, Louis M Staudt
Jun 18, 2002·The Journal of Pharmacology and Experimental Therapeutics·Marina S FeschenkoKathleen J Sweadner
Jun 21, 2002·The New England Journal of Medicine·Andreas RosenwaldUNKNOWN Lymphoma/Leukemia Molecular Profiling Project
Jul 3, 2002·Nature Reviews. Cancer·Igor Vivanco, Charles L Sawyers
Nov 5, 2002·Immunology Letters·Rachel L RoperRichard P Phipps
Dec 21, 2002·The Journal of Biological Chemistry·Marco ContiCatherine Jin
Jan 2, 2003·Molecular and Cellular Biology·Andrew P WengJon C Aster
Feb 27, 2003·Proceedings of the National Academy of Sciences of the United States of America·Ulf KleinRiccardo Dalla-Favera
Mar 26, 2003·Journal of Cellular Physiology·Yoshihide Tsujimoto
Apr 3, 2003·Nature Reviews. Cancer·Clemens A Schmitt
Jun 28, 2003·FEBS Letters·S DremierC Maenhaut
Jul 24, 2003·Proceedings of the National Academy of Sciences of the United States of America·Ann M RangerStanley J Korsmeyer
Oct 31, 2003·Cancer Cell·Ji LuoLewis C Cantley
Feb 6, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jonathan K IvinsDorothy A Long
Jul 21, 2004·Molecular Cell·Kam Y J ZhangGideon Bollag

❮ Previous
Next ❯

Citations

Aug 19, 2006·Current Treatment Options in Oncology·Thomas E Witzig, Scott H Kaufmann
Feb 16, 2010·Nature Genetics·Yuejuan QinPatricia L M Dahia
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Deepak RaiRicardo C T Aguiar
Jun 14, 2008·The Journal of Biological Chemistry·Kyoungja HongDaniel L Altschuler
Apr 2, 2009·The Journal of Biological Chemistry·Sanjeev KumarYury Ladilov
Oct 20, 2010·The Journal of Experimental Medicine·Ana V MileticRobert C Rickert
Mar 10, 2011·Acta Physiologica·P A InselA C Zambon
Feb 2, 2006·Molecular and Cellular Biology·Jiyan ZhangAnning Lin
Nov 16, 2011·Biochemistry. Biokhimii︠a︡·S V Shirshev
Apr 17, 2009·Blood·Sang-Woo KimRicardo C T Aguiar
Jan 1, 2008·Annals of Vascular Diseases·Tiffany T FancherAlan Dardik
Aug 3, 2007·Proceedings of the National Academy of Sciences of the United States of America·Przemyslaw JuszczynskiMargaret A Shipp
Apr 25, 2007·Leukemia & Lymphoma·Daniel MorgenszternIzidore S Lossos
Jun 7, 2005·Expert Review of Molecular Diagnostics·Kai FuWing C Chan
Feb 12, 2008·Cancer Genetics and Cytogenetics·Deepak RaiRicardo C T Aguiar
Sep 27, 2014·Biochimica Et Biophysica Acta·Avinash AppukuttanYury Ladilov
Jun 10, 2008·British Journal of Haematology·Alfred Reiter, Wolfram Klapper
Nov 28, 2008·British Journal of Haematology·Jeremy S AbramsonMargaret A Shipp
Jul 16, 2010·The Journal of Pathology·Azhar R HussainKhawla S Al-Kuraya
Apr 3, 2016·Glia·Damien D Pearse, Zoë A Hughes
Aug 9, 2011·Advances in Hematology·Pinelopi ArgyriouSotirios Papageorgiou
Nov 1, 2005·Drug Discovery Today·Miles D HouslayKam Y J Zhang
Apr 12, 2015·Reproduction : the Official Journal of the Society for the Study of Fertility·Tonny Studsgaard PetersenClaus Yding Andersen

❮ Previous
Next ❯

Related Concepts

Related Feeds

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

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

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.

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.

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.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.