Does primary myelofibrosis involve a defective stem cell niche? From concept to evidence.

Primary myelofibrosis (PMF) is the rarest and the most severe Philadelphia-negative chronic myeloproliferative syndrome. By associating a clonal proliferation and a mobilization of hematopoietic stem cells from bone marrow to spleen with profound alterations of the stroma, PMF is a remarkable model in which deregulation of the stem cell niche is of utmost importance for the disease development. This paper reviews key data suggesting that an imbalance between endosteal and vascular niches participates in the development of clonal stem cell proliferation.

Cellular and molecular mechanisms underlying bone marrow and liver fibrosis: a review.

Chronic fibroproliferative diseases are an important cause of morbidity and mortality in the world. Fibrotic diseases occur in a large variety of vital organs, and the process of fibrosis seems common to all tissues. In all of fibrotic reactions, the underlying cellular and molecular mechanisms involve leukocyte infiltration, the persistence of inflammation in the tissue, and the proliferation of cells with a myofibroblast phenotype.

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.

Altered transcription of the stem cell leukemia gene in myelofibrosis with myeloid metaplasia.

An increased number of circulating CD34+ hematopoietic progenitors with a prominent proliferation of the megakaryocytic (MK) population are the hallmarks of the myeloproliferation in myelofibrosis with myeloid metaplasia (MMM). Analyzing the potential contribution of the stem cell leukemia (SCL) gene in MMM myeloproliferation was doubly interesting for SCL is expressed both in primitive-uncommitted progenitor cells and erythroid/MK cells, its transcription differentially initiating from promoter 1b and 1a, respectively. Our results show that: (i) the expression of SCL transcript is increased in peripheral blood mononuclear cells (PBMCs) from patients; (ii) SCL gene transcription is altered in MMM CD34+ progenitor cells sorted into CD34+CD41+ and CD34+CD41- subpopulations.

Critical review of pathogenetic mechanisms in myelofibrosis with myeloid metaplasia.

Myelofibrosis with myeloid metaplasia is an uncommon chronic myeloproliferative disorder characterized by extramedullary hematopoiesis associated with varying degrees of bone marrow fibrosis (hematopoiesis is clonal and fibrosis is a polyclonal reactive process). The primary defect in a pluripotent stem cell is still unknown. However, advances have been made during the past few years in the knowledge of the pathogenetic mechanisms in this disorder.