Metabolic Effects of JAK1/2 Inhibition in Patients with Myeloproliferative Neoplasms.

Autor: Sapre M; Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA., Tremblay D; Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA., Wilck E; Department of Radiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA., James A; Division of Endocrinology, Diabetes and Bone Disease, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA., Leiter A; Division of Endocrinology, Diabetes and Bone Disease, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA., Coltoff A; Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA., Koshy AG; Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA., Kremyanskaya M; Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.; Tisch Cancer Institute at Mount Sinai, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA., Hoffman R; Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.; Tisch Cancer Institute at Mount Sinai, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA., Mascarenhas JO; Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.; Tisch Cancer Institute at Mount Sinai, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA., Gallagher EJ; Division of Endocrinology, Diabetes and Bone Disease, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA. Emily.Gallagher@mssm.edu.; Tisch Cancer Institute at Mount Sinai, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA. Emily.Gallagher@mssm.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2019 Nov 12; Vol. 9 (1), pp. 16609. Date of Electronic Publication: 2019 Nov 12.
DOI: 10.1038/s41598-019-53056-x
Abstrakt: Ruxolitinib is an FDA approved janus kinase (JAK)1/2 inhibitor used to treat myeloproliferative neoplasms (MPNs), including myelofibrosis and polycythemia vera. We aimed to determine the metabolic consequences of ruxolitinib treatment in patients with MPNs. We performed a retrospective single-center cohort study utilizing an electronic medical record based database of patients who began treatment with ruxolitinib for MPNs from January 2010 to March 2017. We also examined the effects of ruxolitinib on adipose tissue JAK/STAT signaling in a mouse model. 127 patients were identified, of which 69 had data available for weight, and at least one other parameter of interest before, and 72 weeks after starting ruxolitinib. Mean baseline weight was 73.9 ± 17.0 kg, and 78.54 ± 19.1 kg at 72 weeks (p < 0.001). 50% of patients gained >5% body weight. Baseline body mass index (BMI) was 25.8 ± 4.8 kg/m 2 , and 27.5 ± 5.5 kg/m 2 at 72 weeks (p < 0.001). Patients treated with ruxolitinib had a higher systolic blood pressure, serum AST, and ALT at 72 weeks, compared with baseline (p = 0.03, p = 0.01, p = 0.04, respectively). In mice, ruxolitinib decreased basal and GH-stimulated STAT5 phosphorylation in adipose tissue. As pharmacological JAK1/2 inhibitors are being developed and used in clinical practice, it is important to understand their long-term metabolic consequences.
Databáze: MEDLINE
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