William Vainchenker

William Vainchenker, born on 16 December 1947, is a French medical doctor and researcher. He is considered a specialist in hematopoiesis.[1]

William Vainchenker, Member of the French Academy of sciences

Biography

William Vainchenker is Director of Research at Inserm, Hematopoiesis and Stem Cells Unit, Gustave Roussy Institute, Villejuif.

William Vainchenker is best known for his discoveries in the field of malignant blood diseases and the genetic mechanisms responsible for predisposition to myeloproliferative syndromes and leukaemias.

William Vainchenker studied medicine from 1966-1971 in Paris VII University and passed his medical thesis in 1977. At the same time he completed his bachelor's degree in science, then a DEA (master 2) and a postgraduate thesis in science in 1978 in Paris VI University.

He was appointed to the Paris Hospital Boarding School in 1971 and did his hospital internships from 1971 to 1978 with an interruption as a technical assistance cooperator. William Vainchenker then worked as an intern at the Inserm unit headed by Professor Jean Rosa at Henri Mondor Hospital (Créteil) in the team of Mrs Jeanine Breton Gorius where he started working on megacaryocyte differentiation. In 1981 he returned to a university hospital activity in hemato-immunology as head of the clinic in the department of Professor Maxime Seligmann. In 1983 William Vainchenker was recruited as research director at Inserm in Professor Jean Rosa's unit.  In 1993, he took over the management of an Inserm unit at the Gustave Roussy Institute on the theme of experimental haematology, which he managed until 2010. William Vainchenker then remained until now as a researcher in the same Inserm unit at Gustave Roussy. Until now, he has kept a hematology consultation at Saint Louis Hospital.

Scientific contributions

William Vainchenker has always worked on megacaryocyte differentiation with the objective of characterizing the mechanisms that regulate this normal that leads to platelet formation and then transposing these data to human pathology. This allowed him to be the first team to identify and characterize the progenitor of the megacaryocyte line,[2] then to define its different steps and apply these data to the characterization of leukaemias. In parallel, his team has shown that GATA1 is a transcription factor that plays a key role not only in erythroblast but also in megacaryocyte differentiation.[3]

A major theme of his team was to characterize the regulatory factors of megacaryopoiesis. They were able to show with Françoise Wendling that the orphan MPL receptor had as ligand a megacaryopoiesis stimulating factor that had all the characteristics of thrombopoietin, a presumptive humoral factor that physiologically regulates platelet production.[4][5] Thrombopoietin in plasma could then be isolated from its MPL binding by other teams. This allowed them to study in detail: 1) the mechanisms of regulation of plasma thrombopoietin level by the number of platelets in the blood and 2) its function on differentiation, in particular on polyploidization of megacaryocytes.[6][7] These fundamental results have allowed them to better understand the pathophysiology of different hereditary thrombocytopenia.[8]

Having shown that overexpression of thrombopoietin in mice gave a picture similar to myeloproliferative neoplasm,[9] they focused their research on the pathophysiology of these malignant diseases.  This led to the discovery of the JAK2V617F mutation that causes more than 60% of these diseases, in particular more than 90% of Vaquez's Polyglobulias. JAK2 is a kinase associated with cytokine receptors such as MPL or the erythropoietin receptor essential for signalling these receptors and the V617F mutation results in constitutive signalling and is capable of inducing a disease similar to Vaquez's ployglobulia in mice[10][11][12][13] or the erythropoietin receptor essential for the signalling of these receptors and the V617F mutation results in constitutive signalling and is capable of inducing a disease similar to Vaquez's ployglobulia in mice or the erythropoietin receptor essential for the signalling of these receptors and the V617F mutation results to constitutive signalling and is capable of inducing a disease close to Vaquez's ployglobulia in mice or the erythropoietin receptor essential for signalling these receptors and the V617F mutation results in constitutive signalling and is capable of inducing a disease close to Vaquez's ployglobulia in mice. His team then helped to characterize other motor mutations, particularly those of MPL.[14] Most importantly, it has identified the TET2 gene, which can be mutated in association with JAK2V617F in myeloproliferative neoplasms and plays a major role in normal hematopoiesis and in many pathologies.[15][16] With Stefan Constantinescu's team (Brussels), they showed that calreticulin mutations associated with certain myeloproliferative neoplasms modify the function of this chaperone that binds to MPL to activate signaling via JAK2.[17][18]

Finally, working on familial myeloproliferative syndromes,[19] they characterized one of the first locus responsible for the predisposition to myeloproliferative neoplasms and leukaemias with high penetration.[20] William Vainchenker and his collaborators are studying the mechanism of this predisposition linked to the duplication of 5 genes.

Awards and honours

William Vainchenker is the 1994 winner of the European Haematology Association (EHA) Award and the National Cancer League Award. In 2007, he received the William Dameshek Prize from the American Society of Hematology (ASH)[21] and the Allianz-Institut de France Foundation Research Prize.[22] Finally, in 2014, he received, for his entire career, the Inserm honorary prize of [1][23]

He was elected a member of the French Academy of Sciences in December 2013, in the Human Biology and Medical Sciences section.[24] He is Chevalier of the Légion d'Honneur.

References
  1. "Histoire de l'Inserm".
  2. Vainchenker W, Bouguet J, Guichard J, Breton-Gorius J., « Megakaryocyte colony formation from human bone marrow precursors », Blood, 1979 oct;54(4), p. 940-5
  3. Romeo PH, Prandini MH, Joulin V, Mignotte V, Prenant M, Vainchenker W, Marguerie G, Uzan G., « Megakaryocytic and erythrocytic lineages share specific transcription factors », Nature, 1990 mar 29;344(6265), p. 447-9
  4. Wendling F, Maraskovsky E, Debili N, Florindo C, Teepe M, Titeux M, Methia N, Breton-Gorius J, Cosman D, Vainchenker W., « Mpl ligand is a humoral regulator of megakaryocytopoiesis », Nature, 1994 jun 16;369(6481), p. 571-4
  5. Methia N, Louache F, Vainchenker W, Wendling F., « Oligodeoxynucleotides antisense to the proto-oncogene c-mpl specifically inhibit in vitro megakaryocytopoiesis », Blood, 1993 sep 1;82(5), p. 1395-401
  6. Lordier L, Bluteau D, Jalil A, Legrand C, Pan J, Rameau P, Jouni D, Bluteau O, Mercher T, Leon C, Gachet C, Debili N, Vainchenker W, Raslova H, Chang Y., « RUNX1-induced silencing of non-muscle myosin heavy chain IIB contributes to megakaryocyte polyploidization », Nat Commun., 2012 mar 6;3, p. 717
  7. Lordier L, Jalil A, Aurade F, Larbret F, Larghero J, Debili N, Vainchenker W, Chang Y., « Megakaryocyte endomitosis is a failure of late cytokinesis related to defects in the contractile ring and Rho/Rock signaling », Blood, 2008 oct 15;112(8), p. 3164-74
  8. Raslova H, Komura E, Le Couédic JP, Larbret F, Debili N, Feunteun J, Danos O, Albagli O, Vainchenker W, Favier R., « FLI1 monoallelic expression combined with its hemizygous loss underlies Paris-Trousseau/Jacobsen thrombopenia », J Clin Invest., 2004 jul;114(1), p. 77-84
  9. Villeval JL, Cohen-Solal K, Tulliez M, Giraudier S, Guichard J, Burstein SA, Cramer EM, Vainchenker W, Wendling F., « High thrombopoietin production by hematopoietic cells induces a fatal myeloproliferative syndrome in mice », Blood, 1997 dec 1;90(11), p. 4369-83
  10. Hasan S, Lacout C, Marty C, Cuingnet M, Solary E, Vainchenker W, Villeval JL., « JAK2V617F expression in mice amplifies early hematopoietic cells and gives them a competitive advantage that is hampered by IFNα », Blood, 2013 aug 22;122(8), p. 1464-77
  11. Marty C, Lacout C, Martin A, Hasan S, Jacquot S, Birling MC, Vainchenker W, Villeval JL., « Myeloproliferative neoplasm induced by constitutive expression of JAK2V617F in knock-in mice », Blood, 2010 aug 5;116(5), p. 783-7
  12. Dupont S, Massé A, James C, Teyssandier I, Lécluse Y, Larbret F, Ugo V, Saulnier P, Koscielny S, Le Couédic JP, Casadevall N, Vainchenker W, Delhommeau F., « The JAK2 617V>F mutation triggers erythropoietin hypersensitivity and terminal erythroid amplification in primary cells from patients with polycythemia vera », Blood, 2007 aug 1;110(3), p. 1013-21
  13. James C, Ugo V, Le Couédic JP, Staerk J, Delhommeau F, Lacout C, Garçon L, Raslova H, Berger R, Bennaceur-Griscelli A, Villeval JL, Constantinescu SN, Casadevall N, Vainchenker W., « A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera », Nature, 2005 apr 28;434(7037), p. 1144-8
  14. Cabagnols X, Favale F, Pasquier F, Messaoudi K, Defour JP, Ianotto JC, Marzac C, Le Couédic JP, Droin N, Chachoua I, Favier R, Diop MK, Ugo V, Casadevall N, Debili N, Raslova H, Bellanné-Chantelot C, Constantinescu SN, Bluteau O, Plo I, Vainchenker W., « Presence of atypical thrombopoietin receptor (MPL) mutations in triple-negative essential thrombocythemia patients », Blood, 2016 jan 21;127(3), p. 333-42
  15. Quivoron C, Couronné L, Della Valle V, Lopez CK, Plo I, Wagner-Ballon O, Do Cruzeiro M, Delhommeau F, Arnulf B, Stern MH, Godley L, Opolon P, Tilly H, Solary E, Duffourd Y, Dessen P, Merle-Beral H, Nguyen-Khac F, Fontenay M, Vainchenker W, Bastard C, Mercher T, Bernard OA., « TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis », Cancer Cell., 2011 jul 12;20(1), p. 25-38
  16. Delhommeau F, Dupont S, Della Valle V, James C, Trannoy S, Massé A, Kosmider O, Le Couedic JP, Robert F, Alberdi A, Lécluse Y, Plo I, Dreyfus FJ, Marzac C, Casadevall N, Lacombe C, Romana SP, Dessen P, Soulier J, Viguié F, Fontenay M, Vainchenker W, Bernard OA. ., « Mutation in TET2 in myeloid cancers », N Engl J Med., 2009 may 28;360(22), p. 2289-30
  17. Pecquet C, Chachoua I, Roy A, Balligand T, Vertenoeil G, Leroy E, Albu RI, Defour JP, Nivarthi H, Hug E, Xu E, Ould-Amer Y, Mouton C, Colau D, Vertommen D, Shwe MM, Marty C, Plo I, Vainchenker W, Kralovics R, Constantinescu SN., « Calreticulin mutants as oncogenic rogue chaperones for TpoR and traffic-defective pathogenic TpoR mutants », Blood, 2019 mar 22
  18. Marty C, Pecquet C, Nivarthi H, El-Khoury M, Chachoua I, Tulliez M, Villeval JL, Raslova H, Kralovics R, Constantinescu SN, Plo I, Vainchenker W., « Calreticulin mutants in mice induce an MPL-dependent thrombocytosis with frequent progression to myelofibrosis », Blood, 2016 mar 10;127(10), p. 1317-24
  19. Plo I, Zhang Y, Le Couédic JP, Nakatake M, Boulet JM, Itaya M, Smith SO, Debili N, Constantinescu SN, Vainchenker W, Louache F, de Botton S., « An activating mutation in the CSF3R gene induces a hereditary chronic neutrophilia », J Exp Med., 2009 aug 3;206(8), p. 1701-7
  20. Saliba J, Saint-Martin C, Di Stefano A, Lenglet G, Marty C, Keren B, Pasquier F, Valle VD, Secardin L, Leroy G, Mahfoudhi E, Grosjean S, Droin N, Diop M, Dessen P, Charrier S, Palazzo A, Merlevede J, Meniane JC, Delaunay-Darivon C, Fuseau P, Isnard F, Casadevall N, Solary E, Debili N, Bernard OA, Raslova H, Najman A, Vainchenker W, Bellanné-Chantelot C, Plo I., « Germline duplication of ATG2B and GSKIP predisposes to familial myeloid malignancies », Nat Genet., 2015 oct;47(10), p. 1131-40
  21. 18 décembre 2007 - Cancer
  22. Allianz s’engage depuis 30 ans dans la recherche médicale
  23. "Vidéo Prix d'honneur".
  24. "Académie des sciences".
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.