title: Does primary myelofibrosis involve a defective stem cell niche? From concept to evidence.
abstract: 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. Mechanisms by which bone marrow niches are altered with ensuing mobilization and homing of neoplastic hematopoietic stem cells in new or reinitialized niches in the spleen and liver are examined. Differences between signals delivered by both endosteal and vascular niches in the bone marrow and spleen of patients as well as the responsiveness of PMF stem cells to their specific signals are discussed. A proposal for integrating a potential role for the JAK2 mutation in their altered sensitivity is made. A better understanding of the cross talk between stem cells and their niche should imply new therapeutic strategies targeting not only intrinsic defects in stem cell signaling but also regulatory hematopoietic niche-derived signals and, consequently, stem cell proliferation.
authors.affiliation: Laboratoire de Recherche, Center de Transfusion Sanguine des Armeés (CTSA), Hôpital Percy, Clamart, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Lataillade
authors.forename: Olivier
authors.initials: O
authors.lastname: Pierre-Louis
authors.forename: Hans Carl
authors.initials: HC
authors.lastname: Hasselbalch
authors.forename: Georges
authors.initials: G
authors.lastname: Uzan
authors.forename: Claude
authors.initials: C
authors.lastname: Jasmin
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Martyré
authors.forename: Marie-Caroline
authors.initials: MC
authors.lastname: Le Bousse-Kerdilès
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D002450:Cell Communication; D002465:Cell Movement; D049109:Cell Proliferation; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006413:Hematopoietic System; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D051379:Mice; D008954:Models, Biological; D055728:Primary Myelofibrosis / Q000097:blood* / Q000175:diagnosis*; D015398:Signal Transduction
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2