Polymorphonuclear neutrophil and megakaryocyte mutual involvement in myelofibrosis pathogenesis
ABSTRACT The study presented here, performed on the bone marrow from patients with idiopathic myelofibrosis (MF) and on a murine model of MF, demonstrates a pathological interaction between PMN leukocytes and megakaryocyte (Mk), correlated with MF development. The data obtained revealed abnormal subcellular P-selectin distribution, which appeared to correlate with excessive and pathological emperipolesis of PMN leukocytes within Mk, leading to the destruction of Mk storage organelles and leakage of alpha-granular contents into the bone marrow microenvironment. The prominent role of growth factors, PDGF and TGFbeta, stored in the Mk alpha-granular compartment in the generation of MF has been previously largely documented. Both growth factors are essential for the Mk-dependent fibroblast proliferation. The destructive mutual cellular interaction of Mk and PMN leading to the pathological release of PDGF and TGFbeta within the bone marrow microenvironment may participate, through fibroblast activation, to the generation of MF. Therefore, this study provides insight into the possible pathophysiological mechanisms for the genesis of MF.
Leukemia & lymphoma 05/2013; 55(2). DOI:10.3109/10428194.2013.805329 · 2.61 Impact Factor
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ABSTRACT: Although cell-in-cell structure was noted 100 years ago, the molecular mechanisms of 'entering' and the destination of cell-in-cell remain largely unclear. It takes place among the same type of cells (homotypic cell-in-cell) or different types of cells (heterotypic cell-in-cell). Cell-in-cell formation affects both effector cells and their host cells in multiple aspects, while cell-in-cell death is under more intensive investigation. Given that cell-in-cell has an important role in maintaining homeostasis, aberrant cell-in-cell process contributes to the etiopathology in humans. Indeed, cell-in-cell is observed in many pathological processes of human diseases. In this review, we intend to discuss the biological models of cell-in-cell structures under physiological and pathological status.Cell Death & Disease 05/2013; 4:e630. DOI:10.1038/cddis.2013.147 · 5.18 Impact Factor
Chapter: Chronic Idiopathic Myelofibrosis[Show abstract] [Hide abstract]
ABSTRACT: Chronic idiopathic myelofibrosis (CIMF) is a clinico-pathological entity characterized by a stem-cell- derived clonal myeloproliferation, extramedullary hematopoiesis, proliferation of bone marrow stromal components, splenomegaly, and ineffective erythropoiesis. It is the least common of the chronic myeloproliferative disorders and carries the worst prognosis with a median survival of only 4 years. Treatment for most cases is supportive, while androgens, recombinant erythropoietin, steroids and immuno-modulatory drugs are effective approaches for the management of anemia. Splenectomy and involved field irradiation may also be beneficial in carefully selected patients. Cure is only possible following bone marrow transplantation and a number of practical prognostic scores are available for identifying patients that would benefit from this approach. Recently, the use of low intensity conditioning has resulted in prolonged survival and lower transplant- related mortality. Finally, the recent reports of the association of CIMF with a gain-of-function JAK2 mutation opens the door to targeted therapies as well as molecular monitoring of treatment response.03/2007: pages 253-276;