The spleen of patients with myelofibrosis harbors defective mesenchymal stromal cells

Maria Antonietta Avanzini, Vittorio Abbonante, Paolo Catarsi, Irene Dambruoso, Melissa Mantelli, Valentina Poletto, Elisa Lenta, Paola Guglielmelli, Stefania Croce, Lorenzo Cobianchi, Basilio Jemos, Rita Campanelli, Elisa Bonetti, Christian Andrea Di Buduo, Silvia Salmoiraghi, Laura Villani, Margherita Massa, Marina Boni, Rita Zappatore, Alessandra IurloAlessandro Rambaldi, Alessandro Maria Vannucchi, Paolo Bernasconi, Alessandra Balduini, Giovanni Barosi, Vittorio Rosti

Research output: Contribution to journalArticle

Abstract

Splenic hematopoiesis is a major feature in the course of myelofibrosis (MF). In fact, the spleen of patients with MF contains malignant hematopoietic stem cells retaining a complete differentiation program, suggesting both a pivotal role of the spleen in maintaining the disease and a tight regulation of hematopoiesis by the splenic microenvironment, in particular by mesenchymal stromal cells (MSCs). Little is known about splenic MSCs (Sp-MSCs), both in normal and in pathological context. In this work, we have in vitro expanded and characterized Sp-MSCs from 25 patients with MF and 13 healthy subjects (HS). They shared similar phenotype, growth kinetics, and differentiation capacity. However, MF Sp-MSCs expressed significant lower levels of nestin, and favored megakaryocyte (Mk) differentiation in vitro at a larger extent than their normal counterpart. Moreover, they showed a significant upregulation of matrix metalloprotease 2 (MMP2) and fibronectin 1 (FN1) genes both at mRNA expression and at protein level, and, finally, developed genetic abnormalities which were never detected in HS-derived Sp-MSCs. Our data point toward the existence of a defective splenic niche in patients with MF that could be responsible of some pathological features of the disease, including the increased trafficking of CD34+ cells and the expansion of the megakaryocytic lineage.

Original languageEnglish
Pages (from-to)615-622
JournalAmerican Journal of Hematology
Volume93
Issue number5
DOIs
Publication statusPublished - 2018

ASJC Scopus subject areas

  • Hematology

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