The JAK inhibitor ruxolitinib impairs dendritic cell migration via off-target inhibition of ROCK

Leukemia

Volumn 30, Issue 10, 2016, Pages 2119-2123

  Rudolph, J ^a   Heine, A ^a   Quast, T ^b   Kolanus, W ^b   Trebicka, J ^a   Brossart, P ^a   Wolf, D ^a  

^a UNIVERSITY HOSPITAL BONN   (Germany)

^b UNIVERSITY OF BONN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIN; CHEMOKINE RECEPTOR CCR7; PHOSPHOTRANSFERASE; RHO ASSOCIATED COILED COIL KINASE; RUXOLITINIB; TUBULIN; UNCLASSIFIED DRUG; PROTEIN KINASE INHIBITOR; PYRAZOLE DERIVATIVE; RHO KINASE;

ACTIN FILAMENT; CELL ADHESION; CELL BODY; CELL DEDIFFERENTIATION; CELL MATURATION; CELL MIGRATION; CHEMOTAXIS; DENDRITIC CELL; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; EX VIVO STUDY; EXTRACELLULAR MATRIX; FLOW CYTOMETRY; HUMAN; LETTER; LONG TERM EXPOSURE; LYMPH VESSEL; MONOCYTE; POLYMERIZATION; PRIORITY JOURNAL; ANTAGONISTS AND INHIBITORS; CELL MOTION; DRUG EFFECTS; PATHOLOGY;

CELL MOVEMENT; DENDRITIC CELLS; HUMANS; PROTEIN KINASE INHIBITORS; PYRAZOLES; RHO-ASSOCIATED KINASES;

EID: 84976328159     PISSN: 08876924     EISSN: 14765551     Source Type: Journal    
DOI: 10.1038/leu.2016.155     Document Type: Letter

References (15)

1. Tefferi A. Myelofibrosis with myeloid metaplasia. N Engl J Med 2000; 342: 1255-1265.
2. Percy MJ, McMullin MF. The V617F JAK2 mutation and the myeloproliferative disorders. Hematol Oncol 2005; 23: 91-93.
3. Zeiser R, Burchert A, Lengerke C, Verbeek M, Maas-Bauer K, Metzelder SK et al. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: A multicenter survey. Leukemia 2015; 29: 2062-2068.
4. Spoerl S, Mathew NR, Bscheider M, Schmitt-Graeff A, Chen S, Mueller T et al. Activity of therapeutic JAK 1/2 blockade in graft-versus-host disease. Blood 2014; 123: 3832-3842.
5. Parampalli Yajnanarayana S, Stübig T, Cornez I, Alchalby H, Schönberg K, Rudolph J et al. JAK1/2 inhibition impairs T cell function in vitro and in patients with myeloproliferative neoplasms. Br J Haematol 2015; 169: 824-833.
6. Schönberg K, Rudolph J, Vonnahme M, Parampalli Yajnanarayana S, Cornez I, Hejazi M et al. JAK inhibition impairs NK cell function in myeloproliferative neoplasms. Cancer Res 2015; 75: 2187-2199.
7. Heine A, Held SAE, Daecke SN, Wallner S, Yajnanarayana SP, Kurts C et al. The JAKinhibitor ruxolitinib impairs dendritic cell function in vitro and in vivo. Blood 2013; 122: 1192-1202.
8. Randolph GJ, Angeli V, Swartz MA. Dendritic-cell trafficking to lymph nodes through lymphatic vessels. Nat Rev Immunol 2005; 5: 617-628.
9. Sallusto F, Schaerli P, Loetscher P, Schaniel C, Lenig D, Mackay CR et al. Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation. Eur J Immunol 1998; 28: 2760-2769.
10. Förster R, Schubel A, Breitfeld D, Kremmer E, Renner-Müller I, Wolf E et al. CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell 1999; 99: 23-33.
11. Stein JV, Soriano SF, M'Rini C, Nombela-Arrieta C, De Buitrago GG, Rodríguez-Frade JM et al. CCR7-mediated physiological lymphocyte homing involves activation of a tyrosine kinase pathway. Blood 2003; 101: 38-44.
12. Lämmermann T, Bader BL, Monkley SJ, Worbs T, Wedlich-Söldner R, Hirsch K et al. Rapid leukocyte migration by integrin-independent flowing and squeezing. Nature 2008; 453: 51-55.
13. Zhou T, Georgeon S, Moser R, Moore DJ, Caflisch A, Hantschel O. Specificity and mechanism-of-action of the JAK2 tyrosine kinase inhibitors ruxolitinib and SAR302503 (TG101348). Leukemia 2014; 28: 404-407.
14. Vicente-Manzanares M, Ma X, Adelstein RS, Horwitz AR. Non-muscle myosin II takes centre stage in cell adhesion and migration. Nat Rev Mol Cell Biol 2009; 10: 778-790.
15. Nitschké M, Aebischer D, Abadier M, Haener S, Lucic M, Vigl B et al. Differential requirement for ROCK in dendritic cell migration within lymphatic capillaries in steady-state and inflammation. Blood 2012; 120: 2249-2258.