The 5q- syndrome is a myelodysplastic syndrome characterized by a defect in erythroid differentiation. Patients have severe macrocytic anemia, normal or elevated platelet counts, normal or reduced neutrophil counts, erythroid hypoplasia in the bone marrow, and hypolobated micromegakaryocytes ... The 5q- syndrome is a myelodysplastic syndrome characterized by a defect in erythroid differentiation. Patients have severe macrocytic anemia, normal or elevated platelet counts, normal or reduced neutrophil counts, erythroid hypoplasia in the bone marrow, and hypolobated micromegakaryocytes (Ebert et al., 2008).
Van den Berghe et al. (1974) first described refractory macrocytic anemia associated with deletion of the long arm of chromosome 5, which was known as Belgian disease or 'anemie refractaire de type belge.' It was, of course, found ... Van den Berghe et al. (1974) first described refractory macrocytic anemia associated with deletion of the long arm of chromosome 5, which was known as Belgian disease or 'anemie refractaire de type belge.' It was, of course, found not to be limited to Belgium and the 5q- change was found in other hematologic malignancies (see review of Van den Berghe et al., 1985 and Bunn, 1986). Tinegate et al. (1983) counted 34 recorded cases to the time of their report; 25 were female. A characteristic bone marrow finding is the presence of numerous unilobular nucleated megakaryocytes; the nucleus is often eccentric with copious granular cytoplasm exhibiting plentiful production of large platelets. The clinical course is relatively mild. Transformation into acute nonlymphocytic leukemia is rare when there is no other chromosome abnormality than 5q-. Desferrioxamine administration was recommended to lessen the complications of hemosiderosis. Stuart and Mangan (1986) described successful treatment with syngeneic bone marrow transplantation. When first seen at age 29 years, the patient had the picture of pure red cell aplasia and normal marrow karyotype but with hypolobulated megakaryocytic nuclei. The anemia did not respond to any medical therapy. Two years later he showed the 5q- abnormality in 70% and later 100% of marrow metaphases. Because of transfusion-induced hemosiderosis and the availability of a cytogenetically normal monozygotic twin, bone marrow transplantation was performed. The patient's marrow was ablated with a busulfan plus cyclophosphamide regimen used for patients with nonlymphocytic leukemia. Sustained engraftment of cytogenetically normal marrow ensued. The 5q- myelodysplastic syndrome typically occurs in older persons, particularly females. The deletion is usually interstitial; the distal breakpoint is usually in 5q32 and the proximal breakpoint in 5q12-q14. Mathew et al. (1993) reported the experience with 43 consecutive patients seen at the Mayo Clinic in whom the diagnosis was defined by strict morphologic criteria and the finding of a solitary 5q- cytogenetic defect. The median age at diagnosis was 68 years, with a female predominance (7:3). Transfusion-dependence was present in 80% of patients at the time of the diagnosis, and all untransfused patients had macrocytic indices. In contrast, significant neutropenia or thrombocytopenia was rare.
Somatic chromosomal deletions in cancer are thought to indicate the location of tumor suppressor genes, by which a complete loss of gene function occurs through biallelic inactivation. However, in the ... - Haploinsufficiency for Ribosomal Protein S14 Somatic chromosomal deletions in cancer are thought to indicate the location of tumor suppressor genes, by which a complete loss of gene function occurs through biallelic inactivation. However, in the 5q- syndrome, no biallelic inactivation had been identified. Ebert et al. (2008) described an RNA-mediated interference-based approach to discovery of the 5q- disease gene. They found that partial loss of function of the ribosomal subunit protein RPS14 (130620) phenocopied the disease in normal hematopoietic progenitor cells, and also that forced expression of RPS14 rescued the disease phenotype in patient-derived bone marrow cells. In addition, the authors identified a block in the processing of preribosomal RNA in RPS14-deficient cells that is functionally equivalent to the defect in Diamond-Blackfan anemia (105650), linking the molecular pathophysiology of the 5q- syndrome to a congenital syndrome causing bone marrow failure. Ebert et al. (2008) concluded that the 5q- syndrome is caused by defects in ribosomal protein function and suggested that RNA interference screening is an effective strategy for identifying causal haploinsufficiency disease genes. - Haploinsufficiency for MIR145 and MIR146A Starczynowski et al. (2010) postulated that loss of microRNAs (miRNAs) encoded within the CDR in 5q- syndrome may result in haploinsufficiency due to loss of inhibition of their targets. They found that expression of MIR145 (611795) and MIR146A (610566) was reduced in MDS patients with del(5q). Loss of both MIR145 and MIR146A resulted in activation of innate immune signaling due to elevated expression of their respective targets, TIRAP (606252) and TRAF6 (602355). Knockdown of both Mir145 and Mir146a or overexpression of Traf6 in mouse hematopoietic stem/progenitor cells (HSPCs) recapitulated several features of 5q- syndrome, including thrombocytosis, mild neutropenia, and megakaryocytic dysplasia. Starczynowski et al. (2010) concluded that inappropriate activation of innate immune signals in HSPCs due to loss of miRNA-mediated inhibition is involved in several features of 5q- syndrome.