title: Molecular pathology of myelodysplastic syndromes: biology of medullary stromal and hematopoietic cells (review).
abstract: Myelodysplastic syndromes (MDS) have been defined as a disease entity based on clinical features and morphological findings. Despite similarities in clinical manifestations, genetic abnormalities occurring in hematopoietic cells are heterogeneous among the syndromes. However, recent investigations have revealed that there are common biological events in the bone marrow of MDS cases. Most notably, excessive apoptosis of hematopoietic cells was observed to be induced by the bone marrow microenvironment. The apoptosis was mediated by paracrine as well as autocrine factors, suggesting that medullary stromal and hematopoietic cells play a role in the pathology of disease. Pro-inflammatory cytokines, such as TNFα, in the bone marrow microenvironment are predominantly paracrine mediators of apoptosis. Regarding autocrine stimulation mechanisms, it has recently been shown that the deregulation of ribosomal protein is capable of initiating a stress response in the hematopoietic cell through a p53-mediated signaling pathway. Thus, both the stromal cells of the bone marrow microenvironment and hematopoietic cells themselves possess a common and characteristic biology in this heterogeneous disease entity.
authors.affiliation: Department of Comprehensive Pathology, Tokyo Medical and Dental University, Tokyo, Japan. masa.pth2@tmd.ac.jp
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kitagawa
authors.forename: Morito
authors.initials: M
authors.lastname: Kurata
authors.forename: Kouhei
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Shinya
authors.initials: S
authors.lastname: Abe
authors.forename: Shiho
authors.initials: S
authors.lastname: Suzuki
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Umeda
mesh_terms: D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018121:Receptors, Cytokine / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016207:Cytokines; D018121:Receptors, Cytokine; D016159:Tumor Suppressor Protein p53