Myelodysplastic Syndromes
Wojciech Gorczyca in Atlas of Differential Diagnosis in Neoplastic Hematopathology, 2014
Pure red cell aplasia is a rare disease that can be congenital or acquired. The congenital form, called Diamond–Blackfan anemia, seen in childhood is associated with physical abnormalities, such as craniofacial abnormalities and renal or cardiac defects. The acquired chronic form of pure red cell aplasia can be primary or secondary to various factors, including infections, malignancies, collagen vascular disease, or drugs. Large granular lymphocytes (T-LGL) leukemia is the most common underlying hematological malignancy (an associated thymoma is found in up to 22% of patients). The BM is pure red cell aplasia and either hypocellular or normocellular, and typically shows selective decrease or absence of red cell precursors beyond the proerythroblast stage (the maturation of the granulocytic and megakaryocytic series is normal). Iron storage is often increased (due to blood transfusions). There is frequently an increase in hematogones. In parvovirus infections, enlarged proerythroblasts with intranuclear inclusions may be seen and the dyserythropoiesis might very prominent.
Hematological problems in the neonate
Prem Puri in Newborn Surgery, 2017
Diamond–Blackfan anemia frequently presents in infancy with an isolated macrocytic anemia due to pure red cell aplasia. It classically causes reticulocytopenia. About half of these infants also have a variety of congenital anomalies. It is inherited in an autosomal dominant fashion, and the first causative gene, RPS19, was discovered more than 15 years ago. To date, 13 mutations in ribosomal genes have been identified. Red blood cell transfusions are the mainstay of treatment with careful monitoring of iron status to avoid visceral iron overload. HSCT may be considered.14
The White Spotting and Steel Hereditary Anemias of the Mouse
Stephen A. Feig, Melvin H. Freedman in Clinical Disorders and Experimental Models of Erythropoietic Failure, 2019
The administration of Steel factor in vivo results in an increase in the number of hematopoietic cells within a broad range of hematopoietic cell lineages. In rats, for example, Steel factor alone causes an increase in myeloblasts and promyelocytes after a single intravenous injection.79 The combination of Steel factor and G-CSF causes a synergistic myeloid hyperplasia in the bone marrow and spleen and a synergistic increase in circulating neutrophils. The in vivo injection of Steel factor plus GM-CSF results in an increase in marrow neutrophils. In primates Steel factor stimulates an increase in the number of erythrocytes, neutrophils, eosinophils, basophils, monocytes, and lymphocytes in the peripheral blood.80 Taken together, these results demonstrate that Steel factor is a potent cytokine that can stimulate increase in the number of progenitor cells and mature cells of both myeloid and lymphoid lineages in peripheral blood and marrow. These results suggest that Steel factor may play an important clinical role in the treatment of a number of hematopoietic disorders. In this regard, it has been recently observed that the growth of hematopoietic progenitor cells from most, but not all, patients with Diamond-Blackfan anemia, can be stimulated by the addition of Steel factor, together with IL-3 and EPO.72,81,82 Diamond-Blackfan anemia is a congenital disorder of erythropoiesis, associated with macrocytic anemia and other physical anomalies. Steel factor can also induce an increase in the levels of fetal hemoglobin in human BFU-E from sickle cells patients in vitro.3 Thus, if Steel factor is capable of stimulating the growth of erythroid cells in vivo from Diamond-Blackfan patients or increasing the levels of fetal hemoglobin in patients with sickle cell anemia, it might provide an entirely new approach, either alone or in combination with other factors, for the treatment of these and other hematopoietic disorders.
Usefulness of functional splicing analysis to confirm precise disease pathogenesis in Diamond-Blackfan anemia caused by intronic variants in RPS19
Published in Pediatric Hematology and Oncology, 2021
Satoru Takafuji, Takeshi Mori, Noriyuki Nishimura, Nobuyuki Yamamoto, Suguru Uemura, Kandai Nozu, Kiminori Terui, Tsutomu Toki, Etsuro Ito, Hideki Muramatsu, Yoshiyuki Takahashi, Masafumi Matsuo, Tomohiko Yamamura, Kazumoto Iijima
Diamond–Blackfan anemia (DBA) is a rare inherited autosomal dominant bone marrow failure disorder, characterized by normocellular bone marrow with erythroid hypoplasia, congenital anomalies, and a predisposition for malignancies.1,2 Transcriptional abnormalities related to ribosomal dysfunction are the central mechanisms of DBA, and result in TP53 pathway activation.3 DBA is mainly caused by pathogenic variants in ribosomal proteins, and mutations in 20 ribosomal protein genes (RPS19, RPS24, RPS17, RPL35A, RPL5, RPL11, RPS7, RPL26, RPS10, RPS26, RPL15, RPL31, RPS29, RPS28, RPL27, RPS27, RPS15A, RPL35, RPL18, and RPL9) have been identified as responsible for DBA.4–18 Additionally, extremely rare variants in non-ribosomal proteins like TSR2 (a ribosomal maturation factor) and GATA1 (an erythroid transcription factor), have been identified as responsible for DBA.12,19 The most common causative gene of DBA is RPS19. RPS19 reads were mapped to the human reference sequence NM_001022.4. Haploinsufficiency-mediated reduced RPS19 expression causes selective activation of the p53 pathway in erythroid progenitor cells but not in cells from other hematopoietic lineages. Activation of the p53 pathway results in erythroid-specific cell cycle arrest and apoptosis in patients with DBA.20,21
Blessing in disguise; a case of Hereditary Persistence of Fetal Hemoglobin
Published in Journal of Community Hospital Internal Medicine Perspectives, 2018
Irfan Shaukat, Amrit Paudel, Sayf Yassin, Naseruddin Höti, Sadaf Mustafa
Variable increase in HbF with heterogeneous distribution is pathogenic when associated with drugs, chromosomal disorders, hemoglobinopathies, and malignancies. Drugs like hydroxyurea and thalidomide analog pomalidomide increase HbF production. A chromosomal disorder like trisomy 13 is associated with the delayed switch of HbF to HbA and persistently elevated HbF levels [2,3]. Patients with beta thalassemia have a variable increase in HbF determined by the degree of beta chain deficiency and co-inheritance of alpha thalassemia, protecting against the deleterious effects of alpha-globin chain precipitation [4]. Elevated levels may also be found in many patients with leukemias following chemotherapy, considered to be stressed erythropoiesis as observed in juvenile chronic myeloid leukemia (JCML) [5], erythroleukemia occurring in infancy [6], acute myeloblastic leukemia, lymphoblastic leukemia, chronic myeloid leukemia [4] and recipients of bone marrow when donor marrow proliferates [7,8]. Elevated levels of HbF can also be found after treating severe iron deficiency anemia due to acute blood loss [9]. Patients with inherited bone marrow failure syndromes (Diamond-Blackfan anemia, dyskeratosis congenita, Fanconi anemia, Shwachman-Diamond syndrome) often have increased HbF as part of their ‘stressed’ hematopoiesis that also includes macrocytosis and erythropoietin levels higher than predicted by their degree of anemia [10]. Rarely, increased HbF levels have been observed in solid tumors including choriocarcinoma, adenocarcinoma of the lung and hepatoma [11–14].
Sperm RNA elements as markers of health
Published in Systems Biology in Reproductive Medicine, 2018
Rayanne B. Burl, Stephanie Clough, Edward Sendler, Molly Estill, Stephen A. Krawetz
The remaining 10 of 11 SREs associated with a possible disease phenotype, described in Table 3, span a spectrum of diseases from gastrointestinal defects to epilepsy. For example, RPS24 a ribosomal protein that is assembled as part of the 40S ribosomal subunit has also been shown to have extraribosomal functions in vitro. These include, growth regulation, cell proliferation, migration, and invasion [Xu et al. 2016]. Mutations in RPS24 are associated with Diamond-Blackfan anemia (DBA), a rare bone marrow failure syndrome characterized by the absence or decreased number of erythroid bone marrow precursors [Badhai et al. 2009; Da Costa 2001; Lipton and Ellis 2009]. At least 40% of DBA patients present a developmental defect [Badhai et al. 2009; Lipton and Ellis 2009] and DBA is associated with an increased risk of developing malignancies [Badhai et al. 2009; Lipton et al. 2001; Lipton and Ellis 2009]. We are now at a juncture to ask the question: can a sperm RNA profile forecast the future?
Related Knowledge Centers
- Anemia
- Birth Defect
- White Blood Cell
- Platelet
- Bone Marrow
- Neutropenia
- Red Blood Cell
- Aplasia
- Infant
- Shwachman–Diamond Syndrome