TY - JOUR AU - Beatrice Drexler, AU - Jakob R. Passweg, AU - Alexandar Tzankov, AU - Martin Bigler, AU - Alexandre PA Theocharides, AU - Nathan Cantoni, AU - Peter Keller, AU - Georg Stussi, AU - Axel Ruefer, AU - Rudolf Benz, AU - Geneviève Favre, AU - Pontus Lundberg, AU - Ronny Nienhold, AU - Andrea Fuhrer, AU - Christine Biaggi, AU - Markus G. Manz, AU - Mario Bargetzi, AU - Simon Mendez-Ferrer, AU - Radek C. Skoda, PY - 2019/03/31 Y2 - 2024/03/29 TI - The sympathomimetic agonist mirabegron did not lower JAK2-V617F allele burden, but restored nestin-positive cells and reduced reticulin fibrosis in patients with myeloproliferative neoplasms: results of phase II study SAKK 33/14 JF - Haematologica JA - haematol VL - 104 IS - 4 SE - Articles DO - 10.3324/haematol.2018.200014 UR - https://haematologica.org/article/view/8845 SP - 710-716 AB - The β-3 sympathomimetic agonist BRL37344 restored nestin-positive cells within the stem cell niche, and thereby normalized blood counts and improved myelofibrosis in a mouse model of JAK2-V617F-positive myeloproliferative neoplasms. We therefore tested the effectiveness of mirabegron, a β-3 sympathomimetic agonist, in a phase II trial including 39 JAK2-V617F-positive patients with myeloproliferative neoplasms and a mutant allele burden more than 20%. Treatment consisted of mirabegron 50 mg daily for 24 weeks. The primary end point was reduction of JAK2-V617F allele burden of 50% or over, but this was not reached in any of the patients. One patient achieved a 25% reduction in JAK2-V617F allele burden by 24 weeks. A small subgroup of patients showed hematologic improvement. As a side study, bone marrow biopsies were evaluated in 20 patients. We found an increase in the nestin+ cells from a median of 1.09 (interquartile range 0.38-3.27)/mm2 to 3.95 (interquartile range 1.98-8.79)/mm2 (P