Histone deacetylase inhibitors potently repress CXCR4 chemokine receptor expression and function in acute lymphoblastic leukaemia.
The chemokine receptor CXCR4 plays a crucial role in the survival and trafficking of leukaemia cells and requires further attention as human immunodeficiency virus type I (HIV-I) utilises CXCR4 as the major coreceptor for cellular entry. We demonstrated that inhibitors of histone deacetylases, currently being tested in clinical trials for the treatment of various tumours, extensively downregulated CXCR4 protein and mRNA levels in leukaemia cell lines and lymphoblasts from patients with childhood acute leukaemia. As a result, the ability of stromal cell-derived factor-1 to induce cellular migration was impaired. Repression of CXCR4 transcription by inhibitors of histone deacetylases might therefore represent a promising novel approach in the treatment of acute leukaemias.
Crazzolara
Roman
R
Tyrolean Cancer Research Institute (TCRI) at the University of Innsbruck, Department of Paediatrics, Innsbruck University Hospital, Innsbruck, Austria. roman.crazzolara@uibk.ac.at
Jöhrer
Karin
K
Johnstone
Ricky W
RW
Greil
Richard
R
Kofler
Reinhard
R
Meister
Bernhard
B
Bernhard
David
D
D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D002648:Child; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006655:Histone Deacetylases; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019718:Receptors, CXCR4; D006655:Histone Deacetylases