title: Bone marrow niche in immune thrombocytopenia: a focus on megakaryopoiesis.
abstract: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by increased bleeding tendency and thrombocytopenia. In fact, the precise pathogenesis of this disease is still not clear. Megakaryopoiesis involves complete differentiation of megakaryocyte (MK) progenitors to functional platelets. This complex process occurs in specific bone marrow (BM) niches composed of several hematopoietic and non-hematopoietic cell types, soluble factors, and extracellular matrix proteins. These specialized microenvironments sustain MK maturation and localization to sinusoids as well as platelet release into circulation. However, MKs in ITP patients show impaired maturation and signs of degradation. Intrinsic defects in MKs and their extrinsic environment have been implicated in altered megakaryopoiesis in this disease. In particular, aberrant expression of miRNAs directing MK proliferation, differentiation, and platelet production; defective MK apoptosis; and reduced proliferation and differentiation rate of the MSC compartment observed in these patients may account for BM defects in ITP. Furthermore, insufficient production of thrombopoietin is another likely reason for ITP development. Therefore, identifying the signaling pathways and transcription factors influencing the interaction between MKs and BM niche in ITP patients will contribute to increased platelet production in order to prevent incomplete MK maturation and destruction as well as BM fibrosis and apoptosis in ITP. In this review, we will examine the interaction and role of BM niches in orchestrating megakaryopoiesis in ITP patients and discuss how these factors can be exploited to improve the quality of patient treatment and prognosis.
authors.affiliation: Health Research Institute, Thalassemia and Hemoglobinopathy Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Elaheh
authors.initials: E
authors.lastname: Khodadi
authors.affiliation: Health Research Institute, Thalassemia and Hemoglobinopathy Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Ali Amin
authors.initials: AA
authors.lastname: Asnafi
authors.affiliation: Department of Biochemistry and Hematology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
authors.forename: Saeid
authors.initials: S
authors.lastname: Shahrabi
authors.affiliation: Health Research Institute, Thalassemia and Hemoglobinopathy Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shahjahani
authors.affiliation: Health Research Institute, Thalassemia and Hemoglobinopathy Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. najmaldinsaki@gmail.com.
authors.forename: Najmaldin
authors.initials: N
authors.lastname: Saki
mesh_terms: D017209:Apoptosis; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division; D016207:Cytokines / Q000502:physiology; D005355:Fibrosis; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D055153:Stem Cell Niche; D034061:Thrombopoiesis; D013926:Thrombopoietin / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D035683:MicroRNAs; D014157:Transcription Factors; D013926:Thrombopoietin
keywords: Bone marrow niche; Immune thrombocytopenia; Megakaryopoiesis