Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colony assays in methylcellulose (semisolid medium) of erythroid precursors and granulocyte-macrophage precursors from the peripheral blood of 34 patients with beta-thalassemia major and 31 age-matched normal controls were studied. In patients homozygous for beta-thalassemia, a significant increase of circulating erythroid progenitor cells to 3-5 times of normal controls was observed. Furthermore, the number of circulating colony forming units-granulocyte-macrophage (CFU-GM) and colony forming units-mixed (CFU-Mixed) also increased significantly. In these subjects, there was a linear relationship between the number of burst forming units-erythroid (BFU-E) and CFU-GM. The serum level of erythropoietin (EPO) was also significantly higher than that of normal controls (p < 0.05). The increased hematopoiesis, indicated by an increased number of circulating hematopoietic progenitor cells and an elevated serum level of EPO, suggests that the physiologic regulation of erythropoiesis still operated in patients with beta-thalassemia major.
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PMID:Peripheral blood hematopoietic progenitor cells in beta-thalassemia major. 146 Mar 23

Reactivation of fetal hemoglobin (HbF, alpha 2 gamma 2) synthesis was previously reported in normal human adult erythroblast colonies ("bursts") generated by erythroid progenitors (BFU-E) in fetal calf serum-supplemented (FCS+) semisolid cultures stimulated with erythropoietin (Ep). Our studies focused on the reactivation of HbF synthesis in normal adult erythroid bursts generated by peripheral blood mononuclear cells (PBMCs) seeded in FCS+ methylcellulose culture. Reactivation is almost totally suppressed when (a) PBMCs are grown in optimized FCS- culture, or (b) PBMCs are first stringently depleted of monocytes and then plated in FCS+ medium (ie, BFU-E growth in FCS+ Mo- culture). In both experimental conditions, the proliferation of lymphocytes and macrophages interspersed among colonies is drastically reduced, and the cloning efficiency of granulocyte-macrophage (GM) progenitors is sharply diminished. In either case, addition of biosynthetic GM colony-stimulating factor (GM-CSF) induces a dose-related increase of HbF synthesis up to the level in FCS+ culture, with even more elevated values on delayed addition of Ep. A dose-related increase was also observed in erythroblast clones generated by highly purified BFU-E. These results suggest that reactivation of HbF synthesis in normal adults is at least in part mediated by GM-CSF. Furthermore, they imply intriguing hypotheses on the mechanism(s) of perinatal Hb switching. Finally, they raise the possibility of reactivation of HbF synthesis in beta-thalassemia and sickle cell anemia by GM-CSF therapy.
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PMID:Granulocyte-macrophage colony-stimulating factor reactivates fetal hemoglobin synthesis in erythroblast clones from normal adults. 247 26

Molecular genetic techniques permit sensitive assessment of host hematopoiesis after marrow transplantation for thalassemia. Information on this persistence and the cell lines in which it occurs may permit therapeutic intervention in patients at high risk for rejection and/or relapse. The objective of this study, therefore, was to determine the evolution and cell line distribution of persistent mixed chimerism detected in 55 patients treated for beta thalassemia. Our findings indicated that rejection occurred in 20 patients, the host component disappeared in 20, and mixed chimerism without transfusion need persisted for 1 to 7 years in 15. In three patients with stable mixed chimerism for 4, 5, and 7 years, host hematopoiesis fluctuated between 25% and 75%. Despite this, donor pattern beta-globin chain synthesis maintained hemoglobin levels between 10 and 13.5 g/dL without transfusion. In these three patients, the polymerase chain reaction of the VNTR and the fluorescent in situ hybridization analysis revealed the coexistence of donor and host cells in the different peripheral blood cell subpopulations and precursors studied (CD2+, CD4+, CD8+, and CD19+ granulocytes; glycophorin-A+, erythroid burst-forming units, CD33+, granulocyte-macrophage colony-forming units). We found that rejection and disease recurrence occur in approximately one third of patients with early mixed chimerism. High levels of host type hematopoiesis can be present in patients not requiring transfusion.
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PMID:Persistence of mixed chimerism in patients transplanted for the treatment of thalassemia. 860 69

Thalassemia is widely distributed throughout the world and is one of the major public health problems. The use of bone marrow transplantation, the only curative therapy for thalassemia, is limited because less than 30% of the patients have unaffected and HLA-identical siblings as donors. Cord blood stem cells, an alternative source of stem cells for transplantation, have been successfully transplanted into patients with several diseases after myeloablative therapy. Twenty cord blood samples from unaffected neonates whose siblings had severe thalassemia were collected. The median volume was 80 ml. The median number of cells and colony forming units-granulocyte-macrophage in cord blood was 9.2 x 10(8) and 3.4 x 10(5), respectively. Four of 20 cord blood samples had HLA-matched to the affected siblings. One patient underwent cord blood transplantation with success; one patient is waiting for transplantation.
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PMID:Collection of cord blood stem cells for transplantation in thalassemic patients. 874 91

Hematopoietic progenitor cells are present in the blood and the bone marrow. Changes in the numbers of hematopoietic progenitor cells reflect alteration of pluripotent stem cells. We discuss such changes in common hematologic diseases including aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH) and thalassemia. In aplastic anemia, the numbers of burst forming units-erythroid (BFU-E) and colony-forming units-granulocyte-macrophage (CFU-GM) are much decreased; the decrease still exists after recovery from therapy. In PNH, the numbers of progenitor cells are low, even in the presence of marrow hypercellularity. In thalassemia, the numbers of progenitor cells are much increased; more pronounced in splenectomized patients.
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PMID:Hematopoietic progenitor cells in the blood and bone marrow in various hematologic disorders. 1101 54