Abstract
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell malignancies characterized by abnormal hematopoietic cell maturation, increased apoptosis of bone marrow cells, and anemia. The full complement of gene mutations that contribute to the phenotypes or clinical symptoms in MDS is not fully understood. Approximately 10%–25% of MDS patients harbor an interstitial heterozygous deletion on the long arm of chromosome 5, known as del(5q), creating
haploinsufficiency for a large set of genes. Two distinct commonly deleted regions (CDRs) in del(5q), proximal and distal CDR, have been identified. A number of genes in the regions have been implicated in essential for hematopoiesis and pathogenesis of del(5q) MDS through haploinsufficiency. In this paper, we first reviewed the genetics of del(5q) MDS and roles of important genes located in the CDRs that may contribute to abnormal hemopoiesis in patients. Given anemia is one of the significant clinical symptoms presented in MDS patients, thus, we also discussed the possible pathophysiologic causes and currenttreatments of anemia. The HSPA9 gene, encoding the protein mortalin, is located in the proximal CDR. HSPA9/mortalin is heat shock chaperone belonging to the heat shock protein 70 family. Our laboratory has been studying the role of HSPA9 gene in hematopoiesis and erythroid maturation for years. We not only reviewed the scientific findings of HSPA9 that we have been investigated, but also provide perspective in the field. This paper will be helpful for readers to better understand the genetics and pathogenesis of del(5q) MDS, as well as the role of HSPA9/mortalin in diseases.
Keywords
Erythroid maturation, Myelodysplastic syndrome, del(5q), HSPA9/mortalin, TP53/p53