Publication Date:
2016-12-02
Description:
Primary cilia regulate hedgehog (Hh) signal transduction; these sensory organelles being present on most mammalian cells. Aberrant Hh activity has been implicated in malignancy with defective primary cilia expression linked to disease. The role the Hh pathway plays in AML has not been fully elucidated and it is unclear whether AML cells express primary cilia. Our aims were (1) to determine the presence of primary cilia and (2) further evaluate the role of Hh signalling in AML. Primary cilia were identified in all AML (n=23), and 20% of normal (n=10) bone marrow trephines (BMTs) by immunocytochemistry (ICC). Primary cilia were not identified in AML cell lines, primitive (n=4) or mature hematopoietic cells (n=6) isolated from peripheral blood, suggesting they are lost once cells migrate from the bone marrow (BM) microenvironment. Despite the heterogeneity of AML, analysis of 76 primary AML samples demonstrated clear evidence of Hh pathway activity with up regulation of SMO (p5-fold up regulation of genes associated with chemoresistance and poor survival, including MECOM and FOXM1 (both p=0.0001), ABCC1, HOXA3, HOXA9, TWIST1 and SNAIL1 (all p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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