Molecular bases of myelodysplastic syndromes: lessons from animal models.
Myelodysplastic syndrome (MDS) is a clonal disorder of hematopietic stem cells characterized by ineffective hematopoiesis, peripheral blood cytopenia, morphologic dysplasia, and susceptibility to acute myeloid leukemia. Several mechanisms have been suggested as causes of MDS: unbalanced chromosomal abnormalities reflecting a gain or loss of chromosomal material, point mutations of transcription factors, and inactivation of p53. However, appropriate animal models that mimic MDS have long been lacking. We recently reported a novel murine model of MDS that recapitulates trilineage dysplasia and transformation to AML. In this review, we summarize the animal models of MDS and discuss the molecular bases of MDS as well as those of leukemia and myeloproliferative disorders (MPD). J. Cell. Physiol. 219: 529-534, 2009. (c) 2009 Wiley-Liss, Inc.
Komeno
Yukiko
Y
Division of Cellular Therapy, Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
Kitaura
Jiro
J
Kitamura
Toshio
T
D000818:Animals; D016026:Bone Marrow Transplantation; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000235:genetics / Q000473:pathology; D000074008:MDS1 and EVI1 Complex Locus Protein; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D028861:Nuclear Pore Complex Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D011519:Proto-Oncogenes / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C499305:Mecom protein, mouse; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; C465451:Nup98 protein, human; D014157:Transcription Factors; D000090243:Nucleophosmin; C073547:HOXA4 protein, human