| Inducing apoptosis in chemotherapy-resistant B-lineage acute lymphoblastic leukaemia cells by targeting HSPA5, a master regulator of the anti-apoptotic unfolded protein response signalling network. | |
| | |
MedLine Citation:
|
PMID: 21517817 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
We present previously unknown evidence that the immunoglobulin heavy chain binding protein BIP/HSPA5, also known as glucose regulated protein (GRP)78, serving as a pivotal component of the pro-survival axis of the unfolded protein response (UPR) signalling network, is abundantly expressed in relapsed B-lineage acute lymphoblastic leukaemia (ALL) and contributes to chemotherapy resistance of leukaemic B-cell precursors. The resistance of B-lineage ALL cells to the standard anti-leukaemic drug vincristine was overcome by the HSPA5 inhibitor epigallocatechin gallate, which inhibits the anti-apoptotic function of HSPA5 by targeting its ATP-binding domain. Notably, chemotherapy-resistant B-lineage ALL cells underwent apoptosis within 48 h of exposure to a doxorubicin-conjugated cell-penetrating cyclic anti-HSPA5 peptide targeting surface-expressed HSPA5 molecules on leukaemia cells. The identification of the HSPA5 as a chemoresistance biomarker and molecular target for B-lineage ALL may lead to new anti-leukaemic treatment strategies that are much needed. |
| | |
Authors:
|
Fatih M Uckun; Sanjive Qazi; Zahide Ozer; Amanda L Garner; Jason Pitt; Hong Ma; Kim D Janda |
Related Documents
:
|
15343347 - Defective blood dendritic cells in chronic myeloid leukemia correlate with high plasmat... 18958667 - Drug-induced type 1 and type 2 immune responses are characterized by distinct profiles ... 20938757 - Comparative analysis of transduced primary human dendritic cells generated by the use o... 16893947 - Density of dendritic cells in the human tracheal mucosa is age dependent and site speci... 548257 - The effect of perinatal exposure to tetrachlorodibenzo-p-dioxin on the immune response ... 19890387 - A role for immune responses against non-cs components in the cross-species protection i... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-4-25 |
Journal Detail:
|
Title: British journal of haematology Volume: - ISSN: 1365-2141 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
|
Created Date: 2011-4-26 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0372544 Medline TA: Br J Haematol Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
© 2011 Blackwell Publishing Ltd. |
Affiliation:
|
Department of Pediatrics, Division of Hematology-Oncology, University of Southern California Keck School of Medicine, Los Angeles Developmental Therapeutics Program and Systems Immunobiology Laboratory, Childrens Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, CA Department of Biology and Bioinformatics Program, Gustavus Adolphus College, St. Peter, MN Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute of Medical Research (WIRM), The Scripps Research Institute, La Jolla, CA National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Diffusion-weighted imaging for non-invasive and quantitative monitoring of bone marrow infiltration ...
Next Document: Management of Paroxysmal Nocturnal Haemoglobinuria: a personal view.