المؤلفون: Barosi, G, Tefferi, A, Besses, C, Birgegard, G, Cervantes, F, Finazzi, G, Gisslinger, H, Griesshammer, M, Harrison, C, Hehlmann, R, Hermouet, S, Kiladjian, JJ, Kroger, N, Mesa, R, Mc Mullin, MF, Pardanani, A, Passamonti, F, Samuelsson, J, Vannucchi, AM, Reiter, A, Silver, RT, Verstovsek, S, Tognoni, G, Barbui, T

المصدر: Leukemia. 29(1):20-26

مصطلحات موضوعية: Medicin och hälsovetenskap

الوصول الحر: http://kipublications.ki.se/Default.aspx?queryparsed=id:130480588Test

المؤلفون: Barosi, G, Mesa, R, Finazzi, G, Harrison, C, Kiladjian, JJ, Lengfelder, E, McMullin, MF, Passamonti, F, Vannucchi, AM, Besses, C, Gisslinger, H, Samuelsson, J, Verstovsek, S, Hoffman, R, Pardanani, A, Cervantes, F, Tefferi, A, Barbui, T

المصدر: Blood. 121(23):4778-4781

مصطلحات موضوعية: Medicin och hälsovetenskap

الوصول الحر: http://kipublications.ki.se/Default.aspx?queryparsed=id:127146964Test

المؤلفون: Pecquet, C, Papadopoulos, N, Balligand, T, Chachoua, I, Tisserand, A, Vertenoeil, G, Nédélec, A, Vertommen, D, Roy, A, Marty, C, Nivarthi, H, Defour, J-P, El-Khoury, M, Hug, E, Majoros, A, Xu, E, Zagrijtschuk, O, Fertig, TE, Marta, DS, Gisslinger, H, Gisslinger, B, Schalling, M, Casetti, I, Rumi, E, Pietra, D, Cavalloni, C, Arcaini, L, Cazzola, M, Komatsu, N, Kihara, Y, Sunami, Y, Edahiro, Y, Araki, M, Lesyk, R, Buxhofer-Ausch, V, Heibl, S, Pasquier, F, Havelange, V, Plo, I, Vainchenker, W, Kralovics, R, Constantinescu, SN

الوصف: Mutant calreticulin (CALR) proteins resulting from a −1/+2 frameshifting mutation of the CALR exon 9 carry a novel C-terminal amino acid sequence and drive the development of myeloproliferative neoplasms (MPNs). Mutant CALRs were shown to interact with and activate the thrombopoietin receptor (TpoR/MPL) in the same cell. We report that mutant CALR proteins are secreted and can be found in patient plasma at levels up to 160 ng/mL, with a mean of 25.64 ng/mL. Plasma mutant CALR is found in complex with soluble transferrin receptor 1 (sTFR1) that acts as a carrier protein and increases mutant CALR half-life. Recombinant mutant CALR proteins bound and activated the TpoR in cell lines and primary megakaryocytic progenitors from patients with mutated CALR in which they drive thrombopoietin-independent colony formation. Importantly, the CALR-sTFR1 complex remains functional for TpoR activation. By bioluminescence resonance energy transfer assay, we show that mutant CALR proteins produced in 1 cell can specifically interact in trans with the TpoR on a target cell. In comparison with cells that only carry TpoR, cells that carry both TpoR and mutant CALR are hypersensitive to exogenous mutant CALR proteins and respond to levels of mutant CALR proteins similar to those in patient plasma. This is consistent with CALR-mutated cells that expose TpoR carrying immature N-linked sugars at the cell surface. Thus, secreted mutant CALR proteins will act more specifically on the MPN clone. In conclusion, a chaperone, CALR, can turn into a rogue cytokine through somatic mutation of its encoding gene.

العلاقة: https://ora.ox.ac.uk/objects/uuid:5996735f-454d-4fec-a05a-aa6e3aa252ccTest; https://doi.org/10.1182/blood.2022016846Test

الإتاحة: https://doi.org/10.1182/blood.2022016846Test
https://ora.ox.ac.uk/objects/uuid:5996735f-454d-4fec-a05a-aa6e3aa252ccTest

المؤلفون: Vospernik, L., Agis, H., Ay, C., Rüsing, L. Z., Gisslinger, H., Simonitsch-Klupp, I., Krauth, M. T., Riedl, J.

المصدر: GTH Congress 2024 – 68th Annual Meeting of the Society of Thrombosis and Haemostasis Research – Building Bridges in Coagulation ; Hämostaseologie ; ISSN 2567-5761

الإتاحة: https://doi.org/10.1055/s-0044-1779097Test

المؤلفون: Tefferi, A, Al-Ali, H, Barosi, G, Devos, T, Gisslinger, H, Jiang, Q, Kiladjian, J-J, Mesa, R, Passamonti, F, McMullin, M, Ribrag, V, Schiller, G, Vannucchi, A, Zhou, D, Reiser, D, Zhong, J, Gale, R

المصدر: Leukemia. 31(4)

مصطلحات موضوعية: Adult, Aged, Aged, 80 and over, Biomarkers, Erythrocyte Transfusion, Female, Humans, Immunologic Factors, Male, Middle Aged, Myeloproliferative Disorders, Phenotype, Primary Myelofibrosis, Thalidomide, Treatment Outcome, Workflow

الوصف: RBC-transfusion dependence is common in persons with myeloproliferative neoplasm (MPN)-associated myelofibrosis. The objective of this study was to determine the rates of RBC-transfusion independence after therapy with pomalidomide vs placebo in persons with MPN-associated myelofibrosis and RBC-transfusion dependence. Two hundred and fifty-two subjects (intent-to-treat (ITT) population) including 229 subjects confirmed by central review (modified ITT population) were randomly assigned (2:1) to pomalidomide or placebo. Trialists and subjects were blinded to treatment allocation. Primary end point was proportion of subjects achieving RBC-transfusion independence within 6 months. One hundred and fifty-two subjects received pomalidomide and 77 placebo. Response rates were 16% (95% confidence interval (CI), 11, 23%) vs 16% (8, 26%; P=0.87). Response in the pomalidomide cohort was associated with ⩽4 U RBC/28 days (odds ratio (OR)=3.1; 0.9, 11.1), age ⩽65 (OR=2.3; 0.9, 5.5) and type of MPN-associated myelofibrosis (OR=2.6; 0.7, 9.5). Responses in the placebo cohort were associated with ⩽4 U RBC/28 days (OR=8.6; 0.9, 82.3), white blood cell at randomization >25 × 109/l (OR=4.9; 0.8, 28.9) and interval from diagnosis to randomization >2 years (OR=4.9; 1.1, 21.9). Pomalidomide was associated with increased rates of oedema and neutropenia but these adverse effects were manageable. Pomalidomide and placebo had similar RBC-transfusion-independence response rates in persons with MPN-associated RBC-transfusion dependence.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/68k2q7szTest

المؤلفون: Gisslinger, H., Klade, C., Georgiev, P., Krochmalczyk, D., Gercheva-Kyuchukova, L., Egyed, M., Dulicek, P., Illes, A., Pylypenko, H., Sivcheva, L., Mayer, J., Yablokova, V., Empson, V., Krejcy, K., Hasselbalch, H., Kralovics, R., Kiladjian, J.-J.

المصدر: HemaSphere ; volume 6, page 97-98 ; ISSN 2572-9241

الإتاحة: https://doi.org/10.1097/01.hs9.0000843676.80508.b5Test

المؤلفون: Cervantes F., Ross D. M., Radinoff A., Palandri F., Myasnikov A., Vannucchi A. M., Zachee P., Gisslinger H., Komatsu N., Foltz L., Mannelli F., Passamonti F., Gilotti G., Sadek I., Tiwari R., Zor E., Al-Ali H. K.

المساهمون: Cervantes, F., Ross, D. M., Radinoff, A., Palandri, F., Myasnikov, A., Vannucchi, A. M., Zachee, P., Gisslinger, H., Komatsu, N., Foltz, L., Mannelli, F., Passamonti, F., Gilotti, G., Sadek, I., Tiwari, R., Zor, E., Al-Ali, H. K.

الوصف: Anemia is a frequent manifestation of myelofibrosis (MF) and there is an unmet need for effective treatments in anemic MF patients. The REALISE phase 2 study (NCT02966353) evaluated the efficacy and safety of a novel ruxolitinib dosing strategy with a reduced starting dose with delayed up-titration in anemic MF patients. Fifty-one patients with primary MF (66.7%), post-essential thrombocythemia MF (21.6%), or post-polycythemia vera MF (11.8%) with palpable splenomegaly and hemoglobin <10 g/dl were included. Median age was 67 (45–88) years, 41.2% were female, and 18% were transfusion-dependent. Patients received 10 mg ruxolitinib b.i.d. for the first 12 weeks, then up-titrations of up to 25 mg b.i.d. were permitted, based on efficacy and platelet counts. Overall, 70% of patients achieved a ≥50% reduction in palpable spleen length at any time during the study. The most frequent adverse events leading to dose interruption/adjustment were thrombocytopenia (17.6%) and anemia (11.8%). Patients who had a dose increase had greater spleen size and higher white blood cell counts at baseline. Median hemoglobin levels remained stable and transfusion requirements did not increase compared with baseline. These results reinforce the notion that it is unnecessary to delay or withhold ruxolitinib because of co-existent or treatment-emergent anemia.

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34017073; info:eu-repo/semantics/altIdentifier/wos/WOS:000652451300002; volume:35; issue:12; firstpage:3455; lastpage:3465; numberofpages:11; journal:LEUKEMIA; https://hdl.handle.net/11383/2143464Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85106298764

الإتاحة: https://doi.org/10.1038/s41375-021-01261-xTest
https://hdl.handle.net/11383/2143464Test

المؤلفون: Barbui T., Carobbio A., Thiele J., Gangat N., Rumi E., Rambaldi A., Vannucchi A. M., Tefferi A., Jeryczynski G., Mullauer L., Vaidya R., Sulai N. H., Pardanani A., Larson D. R., Cazzola M., Casetti I., Finazzi G., Pieri L., Gisslinger H., Gisslinger B., Rodeghiero F., Ruggeri M., Randi M. L., Bertozzi I., Passamonti F.

المساهمون: Barbui, T., Carobbio, A., Thiele, J., Gangat, N., Rumi, E., Rambaldi, A., Vannucchi, A. M., Tefferi, A., Jeryczynski, G., Mullauer, L., Vaidya, R., Sulai, N. H., Pardanani, A., Larson, D. R., Cazzola, M., Casetti, I., Finazzi, G., Pieri, L., Gisslinger, H., Gisslinger, B., Rodeghiero, F., Ruggeri, M., Randi, M. L., Bertozzi, I., Passamonti, F.

الوصف: We applied a parametric Markov five-state model, on a well-characterized international cohort of 1,545 patients with polycythemia vera (PV; median age 61 years; females 51%), in order to examine the impact of incident thrombosis on the trajectory of death or disease progression. At a median follow-up of 6.9 years, 347 (23%) deaths, 50 (3%) blast phase (BP), and 138 (9%) fibrotic (post-PV MF) transformations were recorded. Incident thrombosis occurred at a rate of 2.62% pt/yr (arterial 1.59% and venous 1.05%). The probability of death, in the first 10 years, for 280 (18%) patients who developed thrombosis during follow-up was 40%, which was two-fold higher than that seen in the absence of thrombosis or any other transition state (20%; p < 0.01); the adverse impact from thrombosis was more apparent for arterial (HR 1.74; p < 0.01) vs venous thrombosis (p=NS) and was independent of other fixed (i.e., age, prior venous thrombosis, leukocytosis) or time-dependent (i.e., progression to BP or MF) risk variables. The transition probability to post-PV MF increased over time, in a linear fashion, with a rate of 5% capped at 5 and 10 years, in patients with or without incident thrombosis, respectively. The impact of thrombosis on transition probability to death or post-PV MF tapered off beyond 10 years and appeared to reverse direction of impact on MF evolution at the 12-year time point. These observations suggest thrombosis in PV to be a marker of aggressive disease biology or a disease-associated inflammatory state that is consequential to both thrombosis and disease progression.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/38102114; info:eu-repo/semantics/altIdentifier/wos/WOS:001125467800001; volume:13; issue:1; firstpage:187; journal:BLOOD CANCER JOURNAL; https://hdl.handle.net/11577/3508655Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85179700627

الإتاحة: https://doi.org/10.1038/s41408-023-00960-1Test
https://hdl.handle.net/11577/3508655Test

المؤلفون: Vannucchi, AM, te Boekhorst, Peter, Harrison, CN, He, GS, Caramella, M, Niederwieser, D, Boyer-Perrard, F, Duan, MH, Francillard, N, Molloy, B, Wroclawska, M, Gisslinger, H

المصدر: Vannucchi , AM , te Boekhorst , P , Harrison , CN , He , GS , Caramella , M , Niederwieser , D , Boyer-Perrard , F , Duan , MH , Francillard , N , Molloy , B , Wroclawska , M & Gisslinger , H 2019 , ' EXPAND, a dose-finding study of ruxolitinib in patients with myelofibrosis and low platelet counts: 48-week follow-up analysis ' , Haematologica , vol. 104 , no. 5 , pp. 947-954 . https://doi.org/10.3324/haematol.2018.204602Test

مصطلحات موضوعية: /dk/atira/pure/keywords/researchprograms/AFL001000/EMCMM024104, name=EMC MM-02-41-04

وصف الملف: application/pdf

العلاقة: https://pure.eur.nl/en/publications/b939f552-eafc-4232-b060-2d69f8feed8fTest

الإتاحة: https://doi.org/10.3324/haematol.2018.204602Test
https://pure.eur.nl/en/publications/b939f552-eafc-4232-b060-2d69f8feed8fTest
https://pure.eur.nl/ws/files/48192730/Repub_116826_O-A.pdfTest
http://hdl.handle.net/1765/116826Test

المؤلفون: Barbui T., Thiele J., Gisslinger H., Orazi A., Vannucchi A. M., Gianelli U., Beham-Schmid C., Tefferi A.

المساهمون: T. Barbui, J. Thiele, H. Gisslinger, A. Orazi, A.M. Vannucchi, U. Gianelli, C. Beham-Schmid, A. Tefferi

مصطلحات موضوعية: bone marrow morphology, clinical data, essential thrombocythaemia, pre-fibrotic myelofibrosi, prognosis, Settore MED/08 - Anatomia Patologica, Settore MED/15 - Malattie del Sangue

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/30847907; info:eu-repo/semantics/altIdentifier/wos/WOS:000474639800025; volume:186; issue:2; firstpage:358; lastpage:360; numberofpages:3; journal:BRITISH JOURNAL OF HAEMATOLOGY; http://hdl.handle.net/2434/677709Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85062787406

الإتاحة: https://doi.org/10.1111/bjh.15840Test
http://hdl.handle.net/2434/677709Test