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

TY - JOUR

T1 - Does primary myelofibrosis involve a defective stem cell niche? From concept to evidence

AU - Lataillade, J.J.

AU - Pierre-Louis, O.

AU - Uzan, G.

AU - Jasmin, C.

AU - Martyre, M.C.

AU - Bousse-Kerdiles, M.C. Le

AU - Hasselbalch, Hans K

N1 - Times Cited: 0ReviewEnglishLe Bousse-Kerdiles, M. CHop Paul Brousse, INSERM, U602, Andre Lwoff Inst, 14 Ave Paul Vaillant Couturier, F-94807 Villejuif, FranceCited References Count: 108357SHAMER SOC HEMATOLOGY1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USAWASHINGTON

PY - 2008

Y1 - 2008

N2 - 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 Udgivelsesdato: 2008/10/15

AB - 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 Udgivelsesdato: 2008/10/15

M3 - Journal article

SN - 0006-4971

VL - 112

SP - 3026

EP - 3035

JO - Blood

JF - Blood

IS - 8

ER -