Primary cilia are present on human blood and bone marrow cells and mediate Hedgehog signaling.
Primary cilia are nonmotile, microtubule-based organelles that are present on the cellular membrane of all eukaryotic cells. Functional cilia are required for the response to developmental signaling pathways such as Hedgehog (Hh) and Wnt/β-catenin. Although the Hh pathway has been shown to be active in leukemia and other blood cancers, there have been no reports describing the presence of primary cilia in human blood or leukemia cells. In the present study, we show that nearly all human blood and bone marrow cells have primary cilia (97-99%). In contrast, primary cilia on AML cell lines (KG1, KG1a, and K562) were less frequent (10-36% of cells) and were often shorter and dysmorphic, with less well-defined basal bodies. Finally, we show that treatment of blood cells with the Hh pathway ligand Sonic Hedgehog (SHh) causes translocation of Smoothened (SMO) to the primary cilia and activation of Hh target genes, demonstrating that primary cilia in blood cells are functional and participate in Hh signaling. Loss of primary cilia on leukemia cells may have important implications for aberrant pathway activation and response to SMO inhibitors currently in clinical development.
Department of Medicine, Division of Hematology, and Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Mohan
M
Singh
Department of Medicine, Division of Hematology, and Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Parvesh
P
Chaudhry
Department of Medicine, Division of Hematology, and Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: akilmerc@usc.edu.
Akil A
AA
Merchant
D000818:Animals; D001773:Blood Cells / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism*; D002460:Cell Line; D002923:Cilia / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D015398:Signal Transduction
D053823:Hedgehog Proteins