Pathological interactions between hematopoietic stem cells and their niche revealed by mouse models of primary myelofibrosis.
Primary myelofibrosis (PMF) belongs to the Philadelphia-negative myeloproliferative neoplasms and is a hematological disorder caused by abnormal function of the hematopoietic stem cells. The disease manifests itself with a plethora of alterations, including anemia, splenomegaly and extramedullary hematopoiesis. Its hallmarks are progressive marrow fibrosis and atypical megakaryocytic hyperplasia, two distinctive features used to clinically monitor disease progression. In an attempt to investigate the role of abnormal megakaryocytopoiesis in the pathogenesis of PMF, several transgenic mouse models have been generated. These models are based either on mutations that interfere with the extrinsic (thrombopoietin and its receptor, MPL) and intrinsic (the GATA1 transcription factor) control of normal megakaryocytopoiesis, or on known genetic lesions associated with the human disease. Here we provide an up-to-date review on the insights into the pathobiology of human PMF achieved by studying these animal models, with particular emphasis on results obtained with Gata1(low) mice.
Varricchio
Lilian
L
Department of Medicine, Division of Hematology/Oncology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1079, New York, NY 10029, USA Tel.: +1 212 241 6974 lilian.varricchio@mssm.edu.
Mancini
Annalisa
A
Migliaccio
Anna Rita
AR