دورية أكاديمية
The Variation in the Traits Ameliorated by Inhibitors of JAK1/2, TGF-β, P-Selectin, and CXCR1/CXCR2 in the Gata1 low Model Suggests That Myelofibrosis Should Be Treated by These Drugs in Combination.
| العنوان: | The Variation in the Traits Ameliorated by Inhibitors of JAK1/2, TGF-β, P-Selectin, and CXCR1/CXCR2 in the Gata1 low Model Suggests That Myelofibrosis Should Be Treated by These Drugs in Combination. |
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| المؤلفون: | Gobbo F; Department of Veterinary Medical Sciences, Alma Mater Studiorum University, 40126 Bologna, Italy., Martelli F; National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, 00161 Rome, Italy., Di Virgilio A; National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, 00161 Rome, Italy., Demaria E; Department of Medical and Surgical Sciences, Alma Mater Studiorum University, 40126 Bologna, Italy., Sarli G; Department of Veterinary Medical Sciences, Alma Mater Studiorum University, 40126 Bologna, Italy., Migliaccio AR; Altius Institute for Biomedical Sciences, Seattle, WA 98121, USA.; Institute of Nanotechnology, National Research Council (Cnr-NANOTEC), c/o Campus Ecotekne, 73100 Lecce, Italy. |
| المصدر: | International journal of molecular sciences [Int J Mol Sci] 2024 Jul 13; Vol. 25 (14). Date of Electronic Publication: 2024 Jul 13. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI, [2000- |
| مواضيع طبية MeSH: | Primary Myelofibrosis*/drug therapy , Primary Myelofibrosis*/metabolism , Primary Myelofibrosis*/pathology , Transforming Growth Factor beta*/metabolism , Janus Kinase 1*/antagonists & inhibitors , Janus Kinase 1*/metabolism , P-Selectin*/metabolism , Receptors, Interleukin-8B*/antagonists & inhibitors , Receptors, Interleukin-8B*/metabolism , Pyrimidines*/pharmacology , Pyrimidines*/therapeutic use, Animals ; Receptors, Interleukin-8A/antagonists & inhibitors ; Receptors, Interleukin-8A/metabolism ; Mice ; Janus Kinase 2/metabolism ; Janus Kinase 2/antagonists & inhibitors ; Nitriles/therapeutic use ; Nitriles/pharmacology ; Disease Models, Animal ; Drug Therapy, Combination ; GATA1 Transcription Factor/metabolism ; GATA1 Transcription Factor/genetics ; Pyrazoles/pharmacology ; Pyrazoles/therapeutic use ; Humans |
| مستخلص: | Studies conducted on animal models have identified several therapeutic targets for myelofibrosis, the most severe of the myeloproliferative neoplasms. Unfortunately, many of the drugs which were effective in pre-clinical settings had modest efficacy when tested in the clinic. This discrepancy suggests that treatment for this disease requires combination therapies. To rationalize possible combinations, the efficacy in the Gata1 low model of drugs currently used for these patients (the JAK1/2 inhibitor Ruxolitinib) was compared with that of drugs targeting other abnormalities, such as p27kip1 (Aplidin), TGF-β (SB431542, inhibiting ALK5 downstream to transforming growth factor beta (TGF-β) signaling and TGF-β trap AVID200), P-selectin (RB40.34), and CXCL1 (Reparixin, inhibiting the CXCL1 receptors CXCR1/2). The comparison was carried out by expressing the endpoints, which had either already been published or had been retrospectively obtained for this study, as the fold change of the values in the corresponding vehicles. In this model, only Ruxolitinib was found to decrease spleen size, only Aplidin and SB431542/AVID200 increased platelet counts, and with the exception of AVID200, all the inhibitors reduced fibrosis and microvessel density. The greatest effects were exerted by Reparixin, which also reduced TGF-β content. None of the drugs reduced osteopetrosis. These results suggest that future therapies for myelofibrosis should consider combining JAK1/2 inhibitors with drugs targeting hematopoietic stem cells (p27Kip1) or the pro-inflammatory milieu (TGF-β or CXCL1). |
| References: | Clin Lymphoma Myeloma Leuk. 2020 Jul;20(7):415-421. (PMID: 32199764) Haematologica. 2016 Sep;101(9):1065-73. (PMID: 27247324) Clin Cancer Res. 2012 Jun 1;18(11):3008-14. (PMID: 22474318) Blood Cancer J. 2015 Mar 13;5:e286. (PMID: 25768401) Cancers (Basel). 2020 Aug 23;12(9):. (PMID: 32842500) Nat Med. 2000 Nov;6(11):1235-40. (PMID: 11062534) N Engl J Med. 2017 Feb 2;376(5):429-439. (PMID: 27959701) Exp Hematol. 2023 Jan;117:43-61. (PMID: 36191885) Blood Adv. 2022 Jun 14;6(11):3321-3328. (PMID: 35358295) J Cell Physiol. 2010 Nov;225(2):490-9. (PMID: 20458749) Mol Biol Cell. 2005 Mar;16(3):1469-80. (PMID: 15647380) Blood Adv. 2023 Mar 28;7(6):943-952. (PMID: 36355805) Biomolecules. 2022 Jan 30;12(2):. (PMID: 35204735) J Histochem Cytochem. 2007 Jul;55(7):745-52. (PMID: 17371937) Development. 2018 Jan 22;145(2):. (PMID: 29358215) Am J Blood Res. 2015 Dec 25;5(2):34-61. (PMID: 27069753) Blood. 2013 Apr 25;121(17):3345-63. (PMID: 23462118) Blood. 2013 Dec 12;122(25):4047-53. (PMID: 24174625) Blood. 2022 May 5;139(18):2797-2815. (PMID: 35286385) Haematologica. 2015 Sep;100(9):1139-45. (PMID: 26069290) Haematologica. 2017 Jan;102(1):7-17. (PMID: 27909216) Nature. 2014 Aug 7;512(7512):78-81. (PMID: 25043017) Blood. 2020 Nov 12;136(20):2296-2307. (PMID: 32766876) Am J Pathol. 2005 Sep;167(3):849-58. (PMID: 16127162) Blood. 2023 May 18;141(20):2508-2519. (PMID: 36800567) Nat Rev Mater. 2021 Apr;6(4):351-370. (PMID: 34950512) Clin Cancer Res. 2019 Dec 1;25(23):6976-6985. (PMID: 31481511) Blood. 2002 Aug 15;100(4):1123-32. (PMID: 12149188) Am J Hematol. 2023 May;98(5):801-821. (PMID: 36680511) IUBMB Life. 2020 Jan;72(1):131-141. (PMID: 31749302) Hemasphere. 2021 Jun 28;5(7):e604. (PMID: 34235401) Am J Respir Cell Mol Biol. 2017 May;56(5):667-679. (PMID: 28459387) Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):7976-81. (PMID: 9223298) Mol Cell Biol. 2010 May;30(9):2229-40. (PMID: 20194624) Nature. 2013 Oct 31;502(7473):637-43. (PMID: 24107994) Bone Marrow Res. 2014;2014:128436. (PMID: 24822129) Am J Physiol Cell Physiol. 2022 Feb 1;322(2):C177-C184. (PMID: 34910601) J Bone Miner Res. 2004 Apr;19(4):652-60. (PMID: 15005853) Blood. 2019 Mar 28;133(13):1427-1435. (PMID: 30728145) Blood. 2022 May 26;139(21):3127-3137. (PMID: 34428274) Haematologica. 2005 Aug;90(8):1128-32. (PMID: 16079113) J Exp Med. 2016 Oct 17;213(11):2259-2267. (PMID: 27811054) Front Oncol. 2022 Mar 22;12:853484. (PMID: 35392239) Stem Cells. 2016 Jan;34(1):67-82. (PMID: 26439305) Br J Haematol. 2007 Nov;139(3):351-62. (PMID: 17910625) J Clin Invest. 2022 Jun 1;132(11):. (PMID: 35439167) EMBO J. 1997 Jul 1;16(13):3965-73. (PMID: 9233806) Blood. 2015 Jun 4;125(23):3542-50. (PMID: 25833962) Blood Cancer J. 2017 Jun 16;7(6):e572. (PMID: 28622305) Cell Stem Cell. 2019 Sep 5;25(3):407-418.e6. (PMID: 31303548) Biochem Pharmacol. 2022 Sep;203:115180. (PMID: 35853497) JCI Insight. 2021 Sep 22;6(18):. (PMID: 34383713) Nat Biotechnol. 2017 Dec;35(12):1202-1210. (PMID: 29131149) Clin Cancer Res. 2008 Nov 1;14(21):6735-41. (PMID: 18980965) Future Oncol. 2015;11(5):719-33. (PMID: 25757677) Front Med (Lausanne). 2023 Apr 28;10:1166758. (PMID: 37188088) Expert Opin Pharmacother. 2023 Apr;24(5):577-585. (PMID: 36922391) Blood. 2013 Jun 13;121(24):4832-7. (PMID: 23570800) Blood. 2007 Aug 1;110(3):986-93. (PMID: 17473062) Nat Cell Biol. 2020 Jan;22(1):38-48. (PMID: 31871321) Blood. 2004 Dec 1;104(12):3573-80. (PMID: 15292068) |
| معلومات مُعتمدة: | P01-CA108671 Natinall Cancer Institute; IG23525 AIRC (Associazione Italiana Ricerca Cancro) |
| فهرسة مساهمة: | Keywords: Gata1; IL-8; P-selectin; TGF-β; megakaryocytes; myelofibrosis |
| المشرفين على المادة: | 0 (Transforming Growth Factor beta) EC 2.7.10.2 (Janus Kinase 1) 0 (P-Selectin) 0 (Receptors, Interleukin-8B) 0 (Pyrimidines) 0 (Receptors, Interleukin-8A) EC 2.7.10.2 (Janus Kinase 2) 0 (Nitriles) 0 (GATA1 Transcription Factor) 82S8X8XX8H (ruxolitinib) 0 (Pyrazoles) |
| تواريخ الأحداث: | Date Created: 20240727 Date Completed: 20240727 Latest Revision: 20240905 |
| رمز التحديث: | 20240905 |
| مُعرف محوري في PubMed: | PMC11277099 |
| DOI: | 10.3390/ijms25147703 |
| PMID: | 39062946 |
| قاعدة البيانات: | MEDLINE |
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