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MPL membrane domain sequencing goes deep.

Constantinescu SN, Varghese LN.

Blood. 2020 Jan 23;135(4):236-237. doi: 10.1182/blood.2019003482. No abstract available.


JAK2 ex13InDel drives oncogenic transformation and is associated with chronic eosinophilic leukemia and polycythemia vera.

Patel AB, Franzini A, Leroy E, Kim SJ, Pomicter AD, Genet L, Xiao M, Yan D, Ahmann JM, Agarwal AM, Clair P, Addada J, Lambert J, Salmon M, Gleich GJ, Cross NCP, Constantinescu SN, O'Hare T, Prchal JT, Deininger MW.

Blood. 2019 Dec 26;134(26):2388-2398. doi: 10.1182/blood.2019001385.


Mechanisms of Progression of Myeloid Preleukemia to Transformed Myeloid Leukemia in Children with Down Syndrome.

Labuhn M, Perkins K, Matzk S, Varghese L, Garnett C, Papaemmanuil E, Metzner M, Kennedy A, Amstislavskiy V, Risch T, Bhayadia R, Samulowski D, Hernandez DC, Stoilova B, Iotchkova V, Oppermann U, Scheer C, Yoshida K, Schwarzer A, Taub JW, Crispino JD, Weiss MJ, Hayashi Y, Taga T, Ito E, Ogawa S, Reinhardt D, Yaspo ML, Campbell PJ, Roberts I, Constantinescu SN, Vyas P, Heckl D, Klusmann JH.

Cancer Cell. 2019 Sep 16;36(3):340. doi: 10.1016/j.ccell.2019.08.014. No abstract available.


Knock-in of murine Calr del52 induces essential thrombocythemia with slow-rising dominance in mice and reveals key role of Calr exon 9 in cardiac development.

Balligand T, Achouri Y, Pecquet C, Gaudray G, Colau D, Hug E, Rahmani Y, Stroobant V, Plo I, Vainchenker W, Kralovics R, Van den Eynde BJ, Defour JP, Constantinescu SN.

Leukemia. 2019 Aug 30. doi: 10.1038/s41375-019-0538-1. [Epub ahead of print]


Prolonged inhibition and incomplete recovery of mitochondrial function in oxazolidinone-treated megakaryoblastic cell lines.

Milosevic TV, Vertenoeil G, Payen VL, Sonveaux P, Tulkens PM, Constantinescu SN, Van Bambeke F.

Int J Antimicrob Agents. 2019 Nov;54(5):661-667. doi: 10.1016/j.ijantimicag.2019.07.021. Epub 2019 Jul 30.


Mechanisms of Progression of Myeloid Preleukemia to Transformed Myeloid Leukemia in Children with Down Syndrome.

Labuhn M, Perkins K, Matzk S, Varghese L, Garnett C, Papaemmanuil E, Metzner M, Kennedy A, Amstislavskiy V, Risch T, Bhayadia R, Samulowski D, Hernandez DC, Stoilova B, Iotchkova V, Oppermann U, Scheer C, Yoshida K, Schwarzer A, Taub JW, Crispino JD, Weiss MJ, Hayashi Y, Taga T, Ito E, Ogawa S, Reinhardt D, Yaspo ML, Campbell PJ, Roberts I, Constantinescu SN, Vyas P, Heckl D, Klusmann JH.

Cancer Cell. 2019 Aug 12;36(2):123-138.e10. doi: 10.1016/j.ccell.2019.06.007. Epub 2019 Jul 11. Erratum in: Cancer Cell. 2019 Sep 16;36(3):340.


The role of the thrombopoietin receptor MPL in myeloproliferative neoplasms: recent findings and potential therapeutic applications.

Vainchenker W, Plo I, Marty C, Varghese LN, Constantinescu SN.

Expert Rev Hematol. 2019 Jun;12(6):437-448. doi: 10.1080/17474086.2019.1617129. Epub 2019 May 22.


Calreticulin mutants as oncogenic rogue chaperones for TpoR and traffic-defective pathogenic TpoR mutants.

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.

Blood. 2019 Jun 20;133(25):2669-2681. doi: 10.1182/blood-2018-09-874578. Epub 2019 Mar 22.


Rare type 1-like and type 2-like calreticulin mutants induce similar myeloproliferative neoplasms as prevalent type 1 and 2 mutants in mice.

Toppaldoddi KR, da Costa Cacemiro M, Bluteau O, Panneau-Schmaltz B, Pioch A, Muller D, Villeval JL, Raslova H, Constantinescu SN, Plo I, Vainchenker W, Marty C.

Oncogene. 2019 Mar;38(10):1651-1660. doi: 10.1038/s41388-018-0538-z. Epub 2018 Oct 19.


Influence of the familial Alzheimer's disease-associated T43I mutation on the transmembrane structure and γ-secretase processing of the C99 peptide.

Tang TC, Kienlen-Campard P, Hu Y, Perrin F, Opsomer R, Octave JN, Constantinescu SN, Smith SO.

J Biol Chem. 2019 Apr 12;294(15):5854-5866. doi: 10.1074/jbc.RA118.006061. Epub 2019 Feb 12.


Differential effect of inhibitory strategies of the V617 mutant of JAK2 on cytokine receptor signaling.

Leroy E, Balligand T, Pecquet C, Mouton C, Colau D, Shiau AK, Dusa A, Constantinescu SN.

J Allergy Clin Immunol. 2019 Jul;144(1):224-235. doi: 10.1016/j.jaci.2018.12.1023. Epub 2019 Jan 29.


The S505A thrombopoietin receptor mutation in childhood hereditary thrombocytosis and essential thrombocythemia is S505N: single letter amino acid code matters.

Defour JP, Levy G, Leroy E, Smith SO, Constantinescu SN.

Leukemia. 2019 Feb;33(2):563-564. doi: 10.1038/s41375-018-0356-x. Epub 2019 Jan 11. No abstract available.


Cooccurring JAK2 V617F and R1063H mutations increase JAK2 signaling and neutrophilia in myeloproliferative neoplasms.

Mambet C, Babosova O, Defour JP, Leroy E, Necula L, Stanca O, Tatic A, Berbec N, Coriu D, Belickova M, Kralova B, Lanikova L, Vesela J, Pecquet C, Saussoy P, Havelange V, Diaconu CC, Divoky V, Constantinescu SN.

Blood. 2018 Dec 20;132(25):2695-2699. doi: 10.1182/blood-2018-04-843060. Epub 2018 Oct 30. No abstract available.


Phenotypic Screening for Inhibitors of a Mutant Thrombopoietin Receptor.

Ngo A, Koay A, Pecquet C, Diaconu CC, Jenkins DA, Shiau AK, Constantinescu SN, Choong ML.

Methods Mol Biol. 2018;1787:53-66. doi: 10.1007/978-1-4939-7847-2_4.


Implications of STAT3 and STAT5 signaling on gene regulation and chromatin remodeling in hematopoietic cancer.

Wingelhofer B, Neubauer HA, Valent P, Han X, Constantinescu SN, Gunning PT, Müller M, Moriggl R.

Leukemia. 2018 Aug;32(8):1713-1726. doi: 10.1038/s41375-018-0117-x. Epub 2018 Mar 27. Review.


Thrombopoietin protects hematopoietic stem cells from retrotransposon-mediated damage by promoting an antiviral response.

Barbieri D, Elvira-Matelot E, Pelinski Y, Genève L, de Laval B, Yogarajah G, Pecquet C, Constantinescu SN, Porteu F.

J Exp Med. 2018 May 7;215(5):1463-1480. doi: 10.1084/jem.20170997. Epub 2018 Apr 3.


JAK inhibitors for the treatment of myeloproliferative neoplasms and other disorders.

Vainchenker W, Leroy E, Gilles L, Marty C, Plo I, Constantinescu SN.

F1000Res. 2018 Jan 17;7:82. doi: 10.12688/f1000research.13167.1. eCollection 2018. Review.


New pathogenic mechanisms induced by germline erythropoietin receptor mutations in primary erythrocytosis.

Pasquier F, Marty C, Balligand T, Verdier F, Grosjean S, Gryshkova V, Raslova H, Constantinescu SN, Casadevall N, Vainchenker W, Bellanné-Chantelot C, Plo I.

Haematologica. 2018 Apr;103(4):575-586. doi: 10.3324/haematol.2017.176370. Epub 2017 Dec 21.


β-Sheet Structure within the Extracellular Domain of C99 Regulates Amyloidogenic Processing.

Hu Y, Kienlen-Campard P, Tang TC, Perrin F, Opsomer R, Decock M, Pan X, Octave JN, Constantinescu SN, Smith SO.

Sci Rep. 2017 Dec 7;7(1):17159. doi: 10.1038/s41598-017-17144-0.


Rethinking JAK2 inhibition: towards novel strategies of more specific and versatile Janus kinase inhibition.

Leroy E, Constantinescu SN.

Leukemia. 2017 Dec;31(12):2853. doi: 10.1038/leu.2017.158.


Mutant JAK3 signaling is increased by loss of wild-type JAK3 or by acquisition of secondary JAK3 mutations in T-ALL.

Degryse S, Bornschein S, de Bock CE, Leroy E, Vanden Bempt M, Demeyer S, Jacobs K, Geerdens E, Gielen O, Soulier J, Harrison CJ, Constantinescu SN, Cools J.

Blood. 2018 Jan 25;131(4):421-425. doi: 10.1182/blood-2017-07-797597. Epub 2017 Nov 29.


An unusual, activating insertion/deletion MPL mutant in primary myelofibrosis.

Defour JP, Hoade Y, Reuther AM, Callaway A, Ward D, Chen F, Constantinescu SN, Cross NCP.

Leukemia. 2017 Aug;31(8):1838-1839. doi: 10.1038/leu.2017.153. Epub 2017 May 22. No abstract available.


The Thrombopoietin Receptor: Structural Basis of Traffic and Activation by Ligand, Mutations, Agonists, and Mutated Calreticulin.

Varghese LN, Defour JP, Pecquet C, Constantinescu SN.

Front Endocrinol (Lausanne). 2017 Mar 31;8:59. doi: 10.3389/fendo.2017.00059. eCollection 2017. Review.


Journal of Cellular and Molecular Medicine: the Future.

Constantinescu SN.

J Cell Mol Med. 2017 Feb;21(2):206-207. doi: 10.1111/jcmm.13075. No abstract available.


Rethinking JAK2 inhibition: towards novel strategies of more specific and versatile Janus kinase inhibition.

Leroy E, Constantinescu SN.

Leukemia. 2017 May;31(5):1023-1038. doi: 10.1038/leu.2017.43. Epub 2017 Jan 25. Review. Erratum in: Leukemia. 2017 Dec;31(12 ):2853.


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

Favale F, Messaoudi K, Varghese LN, Boukour S, Pecquet C, Gryshkova V, Defour JP, Albu RI, Bluteau O, Ballerini P, Leverger G, Plo I, Debili N, Raslova H, Favier R, Constantinescu SN, Vainchenker W.

Blood. 2016 Dec 29;128(26):3146-3158. doi: 10.1182/blood-2016-06-722058. Epub 2016 Nov 10.


A Phenotypic Screen for Small-Molecule Inhibitors of Constitutively Active Mutant Thrombopoietin Receptor Implicated in Myeloproliferative Neoplasms.

Ngo A, Koay AZ, Pecquet C, Diaconu CC, Ould-Amer Y, Huang Q, Kang C, Poulsen A, Lee MA, Jenkins D, Shiau A, Constantinescu SN, Choong ML.

Comb Chem High Throughput Screen. 2016;19(10):824-833. doi: 10.2174/1386207319666161010163825.


Cooperation of germ line JAK2 mutations E846D and R1063H in hereditary erythrocytosis with megakaryocytic atypia.

Kapralova K, Horvathova M, Pecquet C, Fialova Kucerova J, Pospisilova D, Leroy E, Kralova B, Milosevic Feenstra JD, Schischlik F, Kralovics R, Constantinescu SN, Divoky V.

Blood. 2016 Sep 8;128(10):1418-23. doi: 10.1182/blood-2016-02-698951. Epub 2016 Jul 7.


Glycines from the APP GXXXG/GXXXA Transmembrane Motifs Promote Formation of Pathogenic Aβ Oligomers in Cells.

Decock M, Stanga S, Octave JN, Dewachter I, Smith SO, Constantinescu SN, Kienlen-Campard P.

Front Aging Neurosci. 2016 May 10;8:107. doi: 10.3389/fnagi.2016.00107. eCollection 2016.


Recent advances in understanding myelofibrosis and essential thrombocythemia.

Vainchenker W, Constantinescu SN, Plo I.

F1000Res. 2016 Apr 19;5. pii: F1000 Faculty Rev-700. doi: 10.12688/f1000research.8081.1. eCollection 2016. Review.


Uncoupling JAK2 V617F activation from cytokine-induced signalling by modulation of JH2 αC helix.

Leroy E, Dusa A, Colau D, Motamedi A, Cahu X, Mouton C, Huang LJ, Shiau AK, Constantinescu SN.

Biochem J. 2016 Jun 1;473(11):1579-91. doi: 10.1042/BCJ20160085. Epub 2016 Mar 30.


Pathologic activation of thrombopoietin receptor and JAK2-STAT5 pathway by frameshift mutants of mouse calreticulin.

Balligand T, Achouri Y, Pecquet C, Chachoua I, Nivarthi H, Marty C, Vainchenker W, Plo I, Kralovics R, Constantinescu SN.

Leukemia. 2016 Aug;30(8):1775-8. doi: 10.1038/leu.2016.47. Epub 2016 Feb 29. No abstract available.


Thrombopoietin receptor is required for the oncogenic function of CALR mutants.

Nivarthi H, Chen D, Cleary C, Kubesova B, Jäger R, Bogner E, Marty C, Pecquet C, Vainchenker W, Constantinescu SN, Kralovics R.

Leukemia. 2016 Aug;30(8):1759-63. doi: 10.1038/leu.2016.32. Epub 2016 Feb 17. No abstract available.


Thrombopoietin receptor activation by myeloproliferative neoplasm associated calreticulin mutants.

Chachoua I, Pecquet C, El-Khoury M, Nivarthi H, Albu RI, Marty C, Gryshkova V, Defour JP, Vertenoeil G, Ngo A, Koay A, Raslova H, Courtoy PJ, Choong ML, Plo I, Vainchenker W, Kralovics R, Constantinescu SN.

Blood. 2016 Mar 10;127(10):1325-35. doi: 10.1182/blood-2015-11-681932. Epub 2015 Dec 14.


His499 Regulates Dimerization and Prevents Oncogenic Activation by Asparagine Mutations of the Human Thrombopoietin Receptor.

Leroy E, Defour JP, Sato T, Dass S, Gryshkova V, Shwe MM, Staerk J, Constantinescu SN, Smith SO.

J Biol Chem. 2016 Feb 5;291(6):2974-87. doi: 10.1074/jbc.M115.696534. Epub 2015 Dec 1.


Calreticulin mutants in mice induce an MPL-dependent thrombocytosis with frequent progression to myelofibrosis.

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.

Blood. 2016 Mar 10;127(10):1317-24. doi: 10.1182/blood-2015-11-679571. Epub 2015 Nov 25.


Analysis by a highly sensitive split luciferase assay of the regions involved in APP dimerization and its impact on processing.

Decock M, El Haylani L, Stanga S, Dewachter I, Octave JN, Smith SO, Constantinescu SN, Kienlen-Campard P.

FEBS Open Bio. 2015 Sep 6;5:763-73. doi: 10.1016/j.fob.2015.09.002. eCollection 2015.


Presence of atypical thrombopoietin receptor (MPL) mutations in triple-negative essential thrombocythemia patients.

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.

Blood. 2016 Jan 21;127(3):333-42. doi: 10.1182/blood-2015-07-661983. Epub 2015 Oct 8.


Distinct Acute Lymphoblastic Leukemia (ALL)-associated Janus Kinase 3 (JAK3) Mutants Exhibit Different Cytokine-Receptor Requirements and JAK Inhibitor Specificities.

Losdyck E, Hornakova T, Springuel L, Degryse S, Gielen O, Cools J, Constantinescu SN, Flex E, Tartaglia M, Renauld JC, Knoops L.

J Biol Chem. 2015 Nov 27;290(48):29022-34. doi: 10.1074/jbc.M115.670224. Epub 2015 Oct 7.


Oncogenic activation of MPL/thrombopoietin receptor by 17 mutations at W515: implications for myeloproliferative neoplasms.

Defour JP, Chachoua I, Pecquet C, Constantinescu SN.

Leukemia. 2016 May;30(5):1214-6. doi: 10.1038/leu.2015.271. Epub 2015 Oct 6. No abstract available.


Whole-exome sequencing identifies novel MPL and JAK2 mutations in triple-negative myeloproliferative neoplasms.

Milosevic Feenstra JD, Nivarthi H, Gisslinger H, Leroy E, Rumi E, Chachoua I, Bagienski K, Kubesova B, Pietra D, Gisslinger B, Milanesi C, Jäger R, Chen D, Berg T, Schalling M, Schuster M, Bock C, Constantinescu SN, Cazzola M, Kralovics R.

Blood. 2016 Jan 21;127(3):325-32. doi: 10.1182/blood-2015-07-661835. Epub 2015 Sep 30.


Infection Exposure is a Causal Factor in B-cell Precursor Acute Lymphoblastic Leukemia as a Result of Pax5-Inherited Susceptibility.

Martín-Lorenzo A, Hauer J, Vicente-Dueñas C, Auer F, González-Herrero I, García-Ramírez I, Ginzel S, Thiele R, Constantinescu SN, Bartenhagen C, Dugas M, Gombert M, Schäfer D, Blanco O, Mayado A, Orfao A, Alonso-López D, Rivas Jde L, Cobaleda C, García-Cenador MB, García-Criado FJ, Sánchez-García I, Borkhardt A.

Cancer Discov. 2015 Dec;5(12):1328-43. doi: 10.1158/2159-8290.CD-15-0892. Epub 2015 Sep 25.


Oncogenic Drivers in Myeloproliferative Neoplasms: From JAK2 to Calreticulin Mutations.

Cahu X, Constantinescu SN.

Curr Hematol Malig Rep. 2015 Dec;10(4):335-43. doi: 10.1007/s11899-015-0278-x. Review.


Tuning cytokine receptor signaling by re-orienting dimer geometry with surrogate ligands.

Moraga I, Wernig G, Wilmes S, Gryshkova V, Richter CP, Hong WJ, Sinha R, Guo F, Fabionar H, Wehrman TS, Krutzik P, Demharter S, Plo I, Weissman IL, Minary P, Majeti R, Constantinescu SN, Piehler J, Garcia KC.

Cell. 2015 Mar 12;160(6):1196-208. doi: 10.1016/j.cell.2015.02.011. Epub 2015 Feb 26.


Presenilin transmembrane domain 8 conserved AXXXAXXXG motifs are required for the activity of the γ-secretase complex.

Marinangeli C, Tasiaux B, Opsomer R, Hage S, Sodero AO, Dewachter I, Octave JN, Smith SO, Constantinescu SN, Kienlen-Campard P.

J Biol Chem. 2015 Mar 13;290(11):7169-84. doi: 10.1074/jbc.M114.601286. Epub 2015 Jan 22.


Gathering support for critical mass: interleukin 4 receptor signaling requires clustering in endosomes.

Constantinescu SN.

Biophys J. 2014 Dec 2;107(11):2479-80. doi: 10.1016/j.bpj.2014.10.029. Epub 2014 Dec 2. No abstract available.


Cooperating JAK1 and JAK3 mutants increase resistance to JAK inhibitors.

Springuel L, Hornakova T, Losdyck E, Lambert F, Leroy E, Constantinescu SN, Flex E, Tartaglia M, Knoops L, Renauld JC.

Blood. 2014 Dec 18;124(26):3924-31. doi: 10.1182/blood-2014-05-576652. Epub 2014 Oct 28.


Differential association of calreticulin type 1 and type 2 mutations with myelofibrosis and essential thrombocytemia: relevance for disease evolution.

Cabagnols X, Defour JP, Ugo V, Ianotto JC, Mossuz P, Mondet J, Girodon F, Alexandre JH, Mansier O, Viallard JF, Lippert E, Murati A, Mozziconacci MJ, Saussoy P, Vekemans MC, Knoops L, Pasquier F, Ribrag V, Solary E, Plo I, Constantinescu SN, Casadevall N, Vainchenker W, Marzac C, Bluteau O.

Leukemia. 2015 Jan;29(1):249-52. doi: 10.1038/leu.2014.270. Epub 2014 Sep 12. No abstract available.


JAK2 and MPL protein levels determine TPO-induced megakaryocyte proliferation vs differentiation.

Besancenot R, Roos-Weil D, Tonetti C, Abdelouahab H, Lacout C, Pasquier F, Willekens C, Rameau P, Lecluse Y, Micol JB, Constantinescu SN, Vainchenker W, Solary E, Giraudier S.

Blood. 2014 Sep 25;124(13):2104-15. doi: 10.1182/blood-2014-03-559815. Epub 2014 Aug 20.


Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo.

Woll PS, Kjällquist U, Chowdhury O, Doolittle H, Wedge DC, Thongjuea S, Erlandsson R, Ngara M, Anderson K, Deng Q, Mead AJ, Stenson L, Giustacchini A, Duarte S, Giannoulatou E, Taylor S, Karimi M, Scharenberg C, Mortera-Blanco T, Macaulay IC, Clark SA, Dybedal I, Josefsen D, Fenaux P, Hokland P, Holm MS, Cazzola M, Malcovati L, Tauro S, Bowen D, Boultwood J, Pellagatti A, Pimanda JE, Unnikrishnan A, Vyas P, Göhring G, Schlegelberger B, Tobiasson M, Kvalheim G, Constantinescu SN, Nerlov C, Nilsson L, Campbell PJ, Sandberg R, Papaemmanuil E, Hellström-Lindberg E, Linnarsson S, Jacobsen SE.

Cancer Cell. 2014 Jun 16;25(6):794-808. doi: 10.1016/j.ccr.2014.03.036. Epub 2014 May 15. Erratum in: Cancer Cell. 2014 Jun 16;25(6):861. Cancer Cell. 2015 Apr 13;27(4):603-5.

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