An incomplete trafficking defect to the cell-surface leads to paradoxical thrombocytosis for human and murine MPL P106L

Blood

Volumn 128, Issue 26, 2016, Pages 3146-3158

  Favale, Fabrizia ^a,b,c,d   Messaoudi, Kahia ^a,b,c   Varghese, Leila N ^e,f   Boukour, Siham ^a,b,c   Pecquet, Christian ^e,f   Gryshkova, Vitalina ^e,f   Defour, Jean Philippe ^e,f   Albu, Roxana Irina ^e,f   Bluteau, Olivier ^a,b,c   Ballerini, Paola ^g   Leverger, Guy ^g   Plo, Isabelle ^a,b,c   Debili, Najet ^a,b,c   Raslova, Hana ^a,b,c   Favier, Remi ^a,b,c,g   Constantinescu, Stefan N ^e,f   Vainchenker, William ^a,b,c  

^a INSERM   (France)

^b INSTITUT GUSTAVE ROUSSY   (France)

^c Universite Paris Sud   (France)

^d HÔPITAL SAINT ANTOINE   (France)

^e DE DUVE INSTITUTE   (Belgium)

^f LUDWIG INSTITUTE FOR CANCER RESEARCH   (Belgium)

^g ARMAND TROUSSEAU HOSPITAL   (France)

Author keywords

[No Author keywords available]

Indexed keywords

CD34 ANTIGEN; THROMBOPOIETIN; MPL PROTEIN, HUMAN; MPL PROTEIN, MOUSE; THROMBOPOIETIN RECEPTOR;

ANIMAL CELL; ARTICLE; CELL FUNCTION; CELL MIGRATION; CELL SURFACE; CELLULAR DISTRIBUTION; CHILD; CONTROLLED STUDY; FLOW CYTOMETRY; HUMAN; HUMAN CELL; MEGAKARYOCYTE; MOUSE; NONHUMAN; PRESCHOOL CHILD; PRIORITY JOURNAL; THROMBOCYTE; THROMBOCYTOSIS; ANIMAL; CELL LINE; CELL MEMBRANE; DISEASE MODEL; ENDOPLASMIC RETICULUM STRESS; FAMILY; FEMALE; GENETIC TRANSDUCTION; GENETICS; MALE; METABOLISM; MUTATION; PATHOLOGY; PEDIGREE; PROTEIN TRANSPORT; RETROVIRIDAE;

ANIMALS; CELL LINE; CELL MEMBRANE; DISEASE MODELS, ANIMAL; ENDOPLASMIC RETICULUM STRESS; FAMILY; FEMALE; HUMANS; MALE; MEGAKARYOCYTES; MICE; MUTATION; PEDIGREE; PROTEIN TRANSPORT; RECEPTORS, THROMBOPOIETIN; RETROVIRIDAE; THROMBOCYTOSIS; TRANSDUCTION, GENETIC;

EID: 85015062705     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2016-06-722058     Document Type: Article

References (49)

1. Grozovsky R, Giannini S, Falet H, Hoffmeister KM. Regulating billions of blood platelets: glycans and beyond. Blood. 2015;126(16):1877-1884.
2. Kaushansky K. The molecular mechanisms that control thrombopoiesis. J Clin Invest. 2005;115(12):3339-3347.
3. Skoda RC. Thrombocytosis. Hematology Am Soc Hematol Educ Program. 2009:159-167.
4. Skoda RC. Hereditary myeloproliferative disorders. Haematologica. 2010;95(1):6-8.
5. Marty C, Saint-Martin C, Pecquet C, et al. Germline JAK2 mutations in the kinase domain are responsible for hereditary thrombocytosis and are resistant to JAK2 and HSP90 inhibitors. Blood. 2014;123(9):1372-1383.
6. Mead AJ, Chowdhury O, Pecquet C, et al. Impact of isolated germline JAK2V617I mutation on human hematopoiesis. Blood. 2013;121(20):4156-4165.
7. Etheridge SL, Cosgrove ME, Sangkhae V, et al. A novel activating, germline JAK2 mutation, JAK2R564Q, causes familial essential thrombocytosis. Blood. 2014;123(7):1059-1068.
8. Ding J, Komatsu H, Wakita A, et al. Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin. Blood. 2004;103(11):4198-4200.
9. Pasquier F, Cabagnols X, Secardin L, Plo I, Vainchenker W. Myeloproliferative neoplasms: JAK2 signaling pathway as a central target for therapy. Clin Lymphoma Myeloma Leuk. 2014;14(suppl):S23-S35.
10. Wiestner A, Schlemper RJ, van der Maas AP, Skoda RC. An activating splice donor mutation in the thrombopoietin gene causes hereditary thrombocythaemia. Nat Genet. 1998;18(1):49-52.
11. Tiedt R, Coers J, Ziegler S, et al. Pronounced thrombocytosis in transgenic mice expressing reduced levels of Mpl in platelets and terminally differentiated megakaryocytes. Blood. 2009;113(8):1768-1777.
12. Fielder PJ, Gurney AL, Stefanich E, et al. Regulation of thrombopoietin levels by c-mpl-mediated binding to platelets. Blood. 1996;87(6):2154-2161.
13. Fielder PJ, Hass P, Nagel M, et al. Human platelets as a model for the binding and degradation of thrombopoietin. Blood. 1997;89(8):2782-2788.
14. Grozovsky R, Begonja AJ, Liu K, et al. The Ashwell-Morell receptor regulates hepatic thrombopoietin production via JAK2-STAT3 signaling. Nat Med. 2015;21(1):47-54.
15. Meyer SC, Keller MD, Woods BA, et al. Genetic studies reveal an unexpected negative regulatory role for Jak2 in thrombopoiesis. Blood. 2014;124(14):2280-2284.
16. Ng AP, Kauppi M, Metcalf D, et al. Mpl expression on megakaryocytes and platelets is dispensable for thrombopoiesis but essential to prevent myeloproliferation. Proc Natl Acad Sci USA. 2014;111(16):5884-5889.
17. Lannutti BJ, Epp A, Roy J, Chen J, Josephson NC. Incomplete restoration of Mpl expression in the mpl-/- mouse produces partial correction of the stem cell-repopulating defect and paradoxical thrombocytosis. Blood. 2009;113(8):1778-1785.
18. Ihara K, Ishii E, Eguchi M, et al. Identification of mutations in the c-mpl gene in congenital amegakaryocytic thrombocytopenia. Proc Natl Acad Sci USA. 1999;96(6):3132-3136.
19. Ballmaier M, Germeshausen M. Congenital amegakaryocytic thrombocytopenia: clinical presentation, diagnosis, and treatment. Semin Thromb Hemost. 2011;37(6):673-681.
20. Moliterno AR, Williams DM, Gutierrez-Alamillo LI, Salvatori R, Ingersoll RG, Spivak JL. Mpl Baltimore: a thrombopoietin receptor polymorphism associated with thrombocytosis. Proc Natl Acad Sci USA. 2004;101(31):11444-11447.
21. El-Harith el-HA, Roesl C, Ballmaier M, et al. Familial thrombocytosis caused by the novel germ-line mutation p.Pro106Leu in the MPL gene. Br J Haematol. 2009;144(2):185-194.
22. Germeshausen M, Ballmaier M, Welte K. MPL mutations in 23 patients suffering from congenital amegakaryocytic thrombocytopenia: the type of mutation predicts the course of the disease. Hum Mutat. 2006;27(3):296.
23. Fox NE, Lim J, Chen R, Geddis AE. F104S c-Mpl responds to a transmembrane domain-binding thrombopoietin receptor agonist: proof of concept that selected receptor mutations in congenital amegakaryocytic thrombocytopenia can be stimulated with alternative thrombopoietic agents. Exp Hematol. 2010;38(5):384-391.
24. Stockklausner C, Klotter AC, Dickemann N, et al. The thrombopoietin receptor P106L mutation functionally separates receptor signaling activity from thrombopoietin homeostasis. Blood. 2015;125(7):1159-1169.
25. Chachoua I, Pecquet C, El-Khoury M, et al. Thrombopoietin receptor activation by myeloproliferative neoplasm associated calreticulin mutants. Blood. 2016;127(10):1325-1335.
26. Araki M, Yang Y, Masubuchi N, et al. Activation of the thrombopoietin receptor by mutant calreticulin in CALR-mutant myeloproliferative neoplasms. Blood. 2016;127(10):1307-1316.
27. Elf S, Abdelfattah NS, Chen E, et al. Mutant calreticulin requires both its mutant C-terminus and the thrombopoietin receptor for oncogenic transformation. Cancer Discov. 2016;6(4):368-381.
28. Ali A, Bluteau O, Messaoudi K, et al. Thrombocytopenia induced by the histone deacetylase inhibitor abexinostat involves p53-dependent and -independent mechanisms. Cell Death Dis. 2013;4:e738.
29. Pecquet C, Staerk J, Chaligné R, et al. Induction of myeloproliferative disorder and myelofibrosis by thrombopoietin receptor W515 mutants is mediated by cytosolic tyrosine 112 of the receptor. Blood. 2010;115(5):1037-1048.
30. Lacout C, Pisani DF, Tulliez M, Gachelin FM, Vainchenker W, Villeval JL. JAK2V617F expression in murine hematopoietic cells leads to MPD mimicking human PV with secondary myelofibrosis. Blood. 2006;108(5):1652-1660.
31. Gurney AL, Carver-Moore K, de Sauvage FJ, Moore MW. Thrombocytopenia in c-mpl-deficient mice. Science. 1994;265(5177):1445-1447.
32. Abbott C, Huang G, Ellison AR, et al. Mouse monoclonal antibodies against human c-Mpl and characterization for flow cytometry applications. Hybridoma (Larchmt). 2010;29(2):103-113.
33. Besancenot R, Chaligné R, Tonetti C, et al. A senescence-like cell-cycle arrest occurs during megakaryocytic maturation: implications for physiological and pathological megakaryocytic proliferation. PLoS Biol. 2010;8(9):e1000476.
34. Gratama JW, D'hautcourt JL, Mandy F, et al; European Working Group on Clinical Cell Analysis. Flow cytometric quantitation of immunofluorescence intensity: problems and perspectives. Cytometry. 1998;33(2):166-178.
35. Palacios R, Steinmetz M. Il-3-dependent mouse clones that express B-220 surface antigen, contain Ig genes in germ-line configuration, and generate B lymphocytes in vivo. Cell. 1985;41(3):727-734.
36. Pecquet C, Diaconu CC, Staerk J, et al. Thrombopoietin receptor down-modulation by JAK2 V617F: restoration of receptor levels by inhibitors of pathologic JAK2 signaling and of proteasomes. Blood. 2012;119(20):4625-4635.
37. Royer Y, Staerk J, Costuleanu M, Courtoy PJ, Constantinescu SN. Janus kinases affect thrombopoietin receptor cell surface localization and stability. J Biol Chem. 2005;280(29):27251-27261.
38. Varghese LN, Zhang JG, Young SN, et al. Functional characterization of c-Mpl ectodomain mutations that underlie congenital amegakaryocytic thrombocytopenia. Growth Factors. 2014;32(1):18-26.
39. Kuter DJ. New thrombopoietic growth factors. Blood. 2007;109(11):4607-4616.
40. Leroy E, Defour JP, Sato T, et al. His499 regulates dimerization and prevents oncogenic activation by asparagine mutations of the human thrombopoietin receptor. J Biol Chem. 2016; 291(6):2974-2987.
41. Cleyrat C, Darehshouri A, Steinkamp MP, et al. Mpl traffics to the cell surface through conventional and unconventional routes. Traffic. 2014;15(9):961-982.
42. Ding J, Komatsu H, Iida S, et al. The Asn505 mutation of the c-MPL gene, which causes familial essential thrombocythemia, induces autonomous homodimerization of the c-Mpl protein due to strong amino acid polarity. Blood. 2009;114(15):3325-3328.
43. Shkalim-Zemer V, Dgany O, Krasnov T, Yacobovich J, Tamary H. MPL Baltimore mutation and thrombocytosis: case report and literature review. J Pediatr Hematol Oncol. 2013;35(3):e112-e114.
44. Heckl D, Wicke DC, Brugman MH, et al. Lentiviral gene transfer regenerates hematopoietic stem cells in a mouse model for Mpl-deficient aplastic anemia. Blood. 2011;117(14):3737-3747.
45. Wicke DC, Meyer J, Buesche G, et al. Gene therapy of MPL deficiency: challenging balance between leukemia and pancytopenia. Mol Ther. 2010;18(2):343-352.
46. Moliterno AR, Hankins WD, Spivak JL. Impaired expression of the thrombopoietin receptor by platelets from patients with polycythemia vera. N Engl J Med. 1998;338(9):572-580.
47. Moliterno AR, Spivak JL. Posttranslational processing of the thrombopoietin receptor is impaired in polycythemia vera. Blood. 1999;94(8):2555-2561.
48. Moliterno AR, Williams DM, Rogers O, Spivak JL. Molecular mimicry in the chronic myeloproliferative disorders: reciprocity between quantitative JAK2 V617F and Mpl expression. Blood. 2006;108(12):3913-3915.
49. Wang X, Haylock D, Hu CS, et al. A thrombopoietin receptor antagonist is capable of depleting myelofibrosis hematopoietic stem and progenitor cells. Blood. 2016;127(26):3398-3409.