Stem cell dysregulation in myelofibrosis with myeloid metaplasia: current data on growth factor and transcription factor involvement.

Myelofibrosis with myeloid metaplasia (MMM), the rarest Philadelphia chromosome-negative chronic myeloproliferative disorder (MPD), is characterized by extramedullary hematopoiesis and myelofibrosis. The primary molecular defect leading to the clonal amplification of the hematopoietic progenitors is still unknown. In this review, we will focus on current data in favor of a pivotal role for hematopoietic and fibrogenic growth factors and of transcription factors in the dysregulation of the hematopoietic compartment. These data shed novel insight into the genesis of MMM myeloproliferation and led us to propose a model, integrating alterations in the expression and function of nuclear regulatory factors and in the hierarchical and complex network of interactions between hematopoietic cells and stroma in the pathogenetic mechanisms of the disease.