Yvon E. Cayre is a professor of hematology at the University Pierre and Marie Curie, in Paris, France. He was director of research at the National Institute of Health and Medical Research (INSERM) from 1995 to 2007.
He gained extensive clinical and biological experience and developed many researches, in the field of onco-hematology.
Besides his activities in France, Yvon Cayre was a Head of several laboratories in the United States (successively at Memorial Sloan -Kettering Cancer Center / Cornell Medical, Columbia University in New York and the Kimmel Cancer Institute at Thomas Jefferson University in Philadelphia. He was also appointed as a professor ("Ordinario") at the University "La Sapienza" in Rome (Italy) where he was teaching onco-hematology to pediatricians . Yvon Cayre has always been involved in teaching activities. As a professor, he is very concerned with issues of bioethics and is a member of the “Commission de Bioethique Medicale” (Medical Bioethical Committee) at the Central Consistory of Jewish institutions in France.
- At the clinical level, he has always been an active practitioner in France and the United States. Temporarily, he took the administrative responsibility of the clinical hematology department at the Robert Debré University Hospital in Paris.
- At the biological level, he created in 1995 the first laboratory for molecular diagnosis of leukemia at the Armand Trousseau Hospital in Paris. Under his leadership, this laboratory has been designated a reference center for the treatment of leukemia children.
- In research, Yvon Cayre is the author of numerous articles published mainly in journals of excellence. His main work was first developed in the field of immunology: (i) demonstrating for the first time that the T lymphocyte receptor was not formed by the rearrangement of immunoglobulin genes but was organized through a different system; (ii) achieving the first cloning of the Beta 2 microglobulin gene. Subsequently, Yvon Cayre was the first to develop a research strategy for identifying molecular targets for the treatment of leukemia. This work allowed the identification of several important genes in myeloid leukemia, using a subtraction cloning approach. Below are a few examples of such genes.
Myeloblastin /proteinase 3. Myeloblastin/proteinase 3 has been identified as: (i) an important factor in inflammation (more than 400 scientific articles have been published on this protease by various groups ); (ii) contributing to the diagnosis of vasculitis; (iii)a main leukemia antigen which is been used (through a specific peptide, PR1 ) to develop a vaccine against leukemia of the myeloid lineage. It was approved by the FDA for the Phase III clinical trial. Recent publication showed that myeloblastin activity is significantly altered in biopsies of lung adenocarcinoma harboring a KRAS gene mutation. This suggests that myeloblastin is a potential therapeutic target in this type of cancer.
The "Junctional Adhesion Molecule - Like (JAML) protein". We have identified JAML and produced an antibody, HL4E10 which binds to JAML protein expressed on the surface T yδ cells which are key players in tissue homeostasis including anti-tumor surveillance and tissue repair. This leads to an important co-stimulatory signaling through the activation of MAP kinase and the production of cytokines. This results in cell proliferation. Because the HL4E10 antibody is only a co-stimulator for the Tyδ cells , the humanized version could be important clinically to treat diseases associated with dysfunction of Tyδ cells such as chronic non-healing wounds and cancer.
ASB2 (ankyrin -repeat SOCS box containing protein 2). We have cloned and identified ASB-2 as inhibiting growth and promoting commitment in myeloid leukemia cells. ASB2 is a retinoic acid (RA)-induced gene in acute promyelocytic leukemia (APL) cells. The PML-RARalpha translocation which is expressed in APL, strongly enhanced RA-induced ASB-2 mRNA expression. In myeloid leukemia cells, ASB-2 expression induced growth inhibition and chromatin condensation recapitulating early events critical to RA-induced differentiation of APL cells. We have showed that ASB2 is an Elongin BC-interacting protein that can assemble with Cullin 5 and Rbx1 to reconstitute an E3 ubiquitin ligase complex. Mixed Lineage Leukemia (MLL) is a key epigenetic regulator of normal hematopoietic development and chromosomal alterations involving MLL are one of the most common genetic alterations in human leukemia. ASB2, which is a component of the ASB E3 ubiquitin ligase complex, mediates MLL degradation through interaction with PHD/Bromodomain region of MLL. Forced expression of ASB2 degrades MLL and reduces its transactivation activity. In contrast, the MLL-AF9 fusion protein does not interact with ASB2 and is resistant to ASB2 mediated degradation. Increased expression of ASB2 during hematopoietic differentiation is associated with decreased levels of MLL protein and down-regulation of MLL target gens. Knockdown of ASB2 leads to increased expression of HOXA9 and delayed cell differentiation. Data support a model whereby ASB2 contributes to hematopoietic differentiation, in part through MLL degradation and may contribute to leukemogenesis (extracts from “Issues in Hematology/2013 Edition, Published by Scholarly Editions, Atlanta, Georgia).
- Since 2007, Yvon Cayre has developed several devices for isolation of fixed or live rare circulating cells from peripheral blood, as well as a full range of protocols for identifying such cells, i.e. circulating tumor cells (CTCs) from patients with cancer and fetal cells circulating in maternal peripheral blood for the development of prenatal diagnosis.
As a consultant with Biocarecell Technologies, Yvon Cayre has recently developed a new device and is further applications in the field of rare circulating cells.
Kongruttanachok N., Cayre Y.E., Knecht H., and Mai S. Rapid separation of mononuclear Hodgkin from multinuclear Reed-Sternberg cells. Laboratory Hematology, In Press
Adebayo Awe J, Chu Xu1 M,Wechsler J, Benali-Furet N, Cayre YE, Saranchuk J, Drachenberg D, Sabine Mai S. 3D telomeric analysis of isolated circulating tumor cells (CTCs). Translational Oncology, 2013 Feb.; 6(1): 51–65.
Desitter I, Guerrouahen BS, Benali-Furet N, Wechsler J, Jänne PA, Kuang Y, Yanagita M, Wang L, Berkowitz JA, Distel RJ, Cayre YE. A new device for rapid isolation by size and characterization of rare circulating tumor cells. Anticancer Res. 2011 Feb;31(2):427-41.
Guerrouahen, B.S., Futami, M., Vaklavas, C., Kanerva, J., Whichard, Z., Nwawka, K., Blanchard, E.G., Lee, F.Y., Robinson, L.J., Arceci, R., Kornblau, S.M., Wieder, E., Cayre, Y.E., and Corey, S.J. Dasatinib Inhibits The Growth Of Molecularly Heterogeneous Myeloid Leukemias. Clin Cancer Res. 2010;16(4):1149-58.
Gavard L, Beghin D, Forestier F, Cayre Y, Peytavin G, Mandelbrot L, Farinotti R, Gil S. Contribution and limit of the model of perfused cotyledon to the study of placental transfer of drugs. Example of a protease inhibitor of HIV: nelfinavir. Eur J Obstet Gynecol Reprod Biol. 2009 Dec;147(2):157-60.
Denis FM, Benecke A, Di Gioia Y, Touw IP, Cayre YE, Lutz PG. PRAM-1 potentiates arsenic trioxide-induced JNK activation. J Biol Chem. 2005 Mar 11;280(10):9043-8.
Heuze ML, Guibal FC, Banks CA, Conaway JW, Conaway RC, Cayre YE, Benecke A, Lutz PG. ASB2 is an Elongin BC-interacting protein that can assemble with Cullin 5 and Rbx1 to reconstitute an E3 ubiquitin ligase complex. J Biol Chem. 2005 Feb 18;280(7):5468-74
Nguyen M, Trubert CL, Rizk-Rabin M, Rehan VK, Besancon F, Cayre YE, Garabedian M. 1,25-Dihydroxyvitamin D3 and fetal lung maturation: immunogold detection of VDR expression in pneumocytes type II cells and effect on fructose 1,6 bisphosphatase. J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):93-7
Moog-Lutz C, Cave-Riant F, Guibal FC, Breau MA, Di Gioia Y, Couraud PO, Cayre YE, Bourdoulous S, Lutz PG. JAML, a novel protein with characteristics of a junctional adhesion molecule, is induced during differentiation of myeloid leukemia cells. Blood. 2003 Nov 1;102(9):3371-8
Lutz PG, Moog-Lutz C, Cayre YE. Signaling revisited in acute promyelocytic leukemia.
Leukemia. 2002 Oct;16(10):1933-9. Review.
Guibal FC, Moog-Lutz C, Smolewski P, Di Gioia Y, Darzynkiewicz Z, Lutz PG, Cayre YE. ASB-2 inhibits growth and promotes commitment in myeloid leukemia cells. J Biol Chem. 2002 Jan 4;277(1):218-24;
Firat H, Favier R, Adam M, Leverger G, Landman-Parker J, Cayre Y, Douay L. Determination of myeloid antigen expression on childhood acute lymphoblastic leukaemia cells: discrepancies using different monoclonal antibody clones. Leuk Lymphoma. 2001 Jun;42(1-2):75-82.
Moog-Lutz C, Peterson EJ, Lutz PG, Eliason S, Cave-Riant F, Singer A, Di Gioia Y, Dmowski S, Kamens J, *Cayre YE, *Koretzky G. PRAM-1 is a novel adaptor protein regulated by retinoic acid (RA) and promyelocytic leukemia (PML)-RA receptor alpha in acute promyelocytic leukemia cells.J Biol Chem. 2001 Jun 22;276(25):22375-81. (* indicates equal last authors)
Lutz PG, Houzel-Charavel A, Moog-Lutz C, Cayre YE. Myeloblastin is an Myb target gene: mechanisms of regulation in myeloid leukemia cells growth-arrested by retinoic acid. Blood. 2001 Apr 15;97(8):2449-56
Ballerini P, Landman Parker J, Laurendeau I, Olivi M, Vidaud M, Adam M, Leverger G, Gerota I, Cayre YE, Bieche I. Quantitative analysis of TEL/AML1 fusion transcripts by real-time RT-PCR assay in childhood acute lymphoblastic leukemia. Leukemia. 2000 Aug;14(8):1526-8
Ye F, Bourgeade MF, Cayre YE, Thang MN. A protein kinase C-independent pathway leading to c-Jun-dependent expression of 100-kDa Ras GTPase-activating protein in JEG-3 human choriocarcinoma cells. Eur J Biochem. 2000 Mar;267(6):1589-97.
Lutz PG, Moog-Lutz C, Coumau-Gatbois E, Kobari L, Di Gioia Y, Cayre YE. Myeloblastin is a granulocyte colony-stimulating factor-responsive gene conferring factor-independent growth to hematopoietic cells. Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1601-6.
Ye F, Cayre YE, Thang MN. Evidence for a novel RasGAP-associated protein of 105 kDa in both mature trophoblasts and differentiating choriocarcinoma cells. Biochem Biophys Res Commun. 1999 Sep 24;263(2):523-7.
Just J, Moog-Lutz C, Houzel-Charavel A, Canteloup S, Grimfeld A, Witko-Sarsat V, Cayre YE. Proteinase 3 mRNA expression is induced in monocytes but not in neutrophils of patients with cystic fibrosis. FEBS Lett. 1999 Sep 3;457(3):437-40.
Atfi A, Prunier C, Mazars A, Defachelles AS, Cayre Y, Gespach C, Bourgeade MF. The oncogenic TEL/PDGFR beta fusion protein induces cell death through JNK/SAPK pathway. Oncogene. 1999 Jul 1;18(26):3878-85.
Favier R, Neonato MG, Maillet F, Feingold J, Cayre Y, Girot R. Incidence of G20210A mutation in severe vaso-occlusive events complicating sickle cell anemia. Blood Coagul Fibrinolysis. 1999 Mar;10(2):111-2.
Belaaouaj A, Moog-Lutz C, Just J, Houzel-Charavel A, Shapiro SD, Cayre Y. Genomic organization and chromosomal localization of mouse proteinase 3 (Myeloblastin). Mamm Genome. 1999 Mar;10(3):210-2.
Besancon F, Atfi A, Gespach C, Cayre YE, Bourgeade MF. Evidence for a role of NF-kappaB in the survival of hematopoietic cells mediated by interleukin 3 and the oncogenic TEL/platelet-derived growth factor receptor beta fusion protein. Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8081-6.
Bourgeade MF, Defachelles AS, Cayre YE. Myc is essential for transformation by TEL/platelet-derived growth factor receptor beta (PDGFRbeta). Blood. 1998 May 1;91(9):3333-9.
Baruchel A, Cayuela JM, Ballerini P, Landman-Parker J, Cezard V, Firat H, Haddad E, Auclerc MF, Valensi F, Cayre YE, Macintyre EA, Sigaux F. The majority of myeloid-antigen-positive (My+) childhood B-cell precursor acute lymphoblastic leukaemias express TEL-AML1 fusion transcripts. Br J Haematol. 1997 Oct;99(1):101-6.
Besancon F, Just J, Bourgeade MF, Van Weyenbergh J, Solomon D, Guillozo H, Wietzerbin J, Cayre YE. HIV-1 p17 and IFN-gamma both induce fructose 1,6-bisphosphatase. J Interferon Cytokine Res. 1997 Aug;17(8):461-7.
Ballerini P, Besancon F, Cayre YE. [Effect of translocation t(15;17) on the gene expression regulation of myeloblastin during all trans retinoic acid induced myeloid differentiation in human leukemic cells] C R Seances Soc Biol Fil. 1995;189(4):521-30.
Labbaye C, Valtieri M, Testa U, Giampaolo A, Meccia E, Sterpetti P, Parolini I, Pelosi E, Bulgarini D, Cayre YE. Retinoic acid downmodulates erythroid differentiation and GATA1 expression in purified adult-progenitor culture. Blood. 1994 Feb 1;83(3):651-6.
Labbaye C, Zhang J, Casanova JL, Lanotte M, Teng J, Miller WH Jr, Cayre YE. Regulation of myeloblastin messenger RNA expression in myeloid leukemia cells treated with all-trans retinoic acid. Blood. 1993 Jan 15;81(2):475-81.
Labbaye C, Musette P, Cayre YE. Wegener autoantigen and myeloblastin are encoded by a single mRNA. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9253-6.
Solomon DH, O'Driscoll K, Sosne G, Weinstein IB, Cayre YE. 1 alpha,25-dihydroxyvitamin D3-induced regulation of protein kinase C gene expression during HL-60 cell differentiation.
Cell Growth Differ. 1991 Apr;2(4):187-94.
Musette P, Labbaye C, Dorner MH, Cayre YE, Casanova JL, Kourilsky P. Wegener's autoantigen and leukemia. Blood. 1991 Mar 15;77(6):1398-9.
Mabondzo A, Le Naour R, Raoul H, Clayette P, Lafuma C, Barre-Sinoussi FC, Cayre Y, Dormont D. In vitro infection of macrophages by HIV: correlation with cellular activation, synthesis of tumour necrosis factor alpha and proteolytic activity. Res Virol. 1991 Mar-Jun;142(2-3):205-12.
Bories D, Raynal MC, Solomon DH, Darzynkiewicz Z, Cayre YE. Down-regulation of a serine protease, myeloblastin, causes growth arrest and differentiation of promyelocytic leukemia cells.
Cell. 1989 Dec 22;59(6):959-68.
Marker AJ, Colosia AD, Tauler A, Solomon DH, Cayre Y, Lange AJ, el-Maghrabi MR, Pilkis SJ. Glucocorticoid regulation of hepatic 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene expression. J Biol Chem. 1989 Apr 25;264(12):7000-4.
Solomon DH, Raynal MC, Tejwani GA, Cayre YE. Activation of the fructose 1,6-bisphosphatase gene by 1,25-dihydroxyvitamin D3 during monocytic differentiation. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6904-8.
Makowske M, Ballester R, Cayre Y, Rosen OM. Immunochemical evidence that three protein kinase C isozymes increase in abundance during HL-60 differentiation induced by dimethyl sulfoxide and retinoic acid. J Biol Chem. 1988 Mar 5;263(7):3402-10.
Steffen M, Cayre Y, Manogue KR, Moore MA. 1,25-Dihydroxyvitamin D3 transcriptionally regulates tumour necrosis factor mRNA during HL-60 cell differentiation. Immunology. 1988 Jan;63(1):43-6.
Cayre Y, Raynal MC, Darzynkiewicz Z, Dorner MH. Model for intermediate steps in monocytic differentiation: c-myc, c-fms, and ferritin as markers. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7619-23.
Silverstone AE, Cayre Y. Phenotyping the prothymocyte. Surv Immunol Res. 1985;4(1):11-8.
Blouquit Y, Delanoe-Garin J, Lacombe C, Arous N, Cayre Y, Peduzzi J, Braconnier F, Galacteros F. Structural study of hemoglobin Hazebrouck, beta 38(C4)Thr----Pro. A new abnormal hemoglobin with instability and low oxygen affinity. FEBS Lett. 1984 Jul 9;172(2):155-8.
Daniel F, Morello D, Le Bail O, Chambon P, Cayre Y, Kourilsky P. Structure and expression of the mouse beta 2-microglobulin gene isolated from somatic and non-expressing teratocarcinoma cells. EMBO J. 1983;2(7):1061-5.
Morello D, Daniel F, Baldacci P, Cayre Y, Gachelin G, Kourilsky P. Absence of significant H-2 and beta 2-microglobulin mRNA expression by mouse embryonal carcinoma cells. Nature. 1982 Mar 18;296(5854):260-2.
Koo GC, Cayre Y, Mittl LR. Comparative study of splenic natural killer cells and prothymocytes.
Cell Immunol. 1981 Jul 15;62(1):164-71.
Cayre Y, Palladino MA, Marcu KB, Stavnezer J. Expression of an antigen receptor on T cells does not require recombination at the immunoglobulin JH-C mu locus. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3814-8.
Cayre Y, de Sostoa A, Silverstone AE. Isolation of a subset of thymocytes inducible for terminal transferase biosynthesis. J Immunol. 1981 Feb;126(2):553-6.
Chenal C, Binet JL, Dighiero G, Leporrier M, Debre P, Merle Beral H, Cayre Y, Guerin RA. Total body irradiation in eight cases of advanced chronic lymphocytic leukamia. Biomedicine. 1979 Apr;31(2):31-2.
Kongruttanachok N., Cayre Y.E., Knecht H., and Mai S. Rapid separation of mononuclear Hodgkin from multinuclear Reed-Sternberg cells. In Press, Laboratory Hematology