Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A systematic study of dyserythropoietic conditions has been conducted in the light of present knowledge and the author's experience. Cytomorphologic and cytochemical investigations have been made of the following hemopathies: 1. primary idiopathic dyserythropoietic anemia morphologically similar to types I, II and III but noncongenital and without a positive acidified-serum test; 2. a special form of dyserythropoietic anemia associated with dyshemopoietic genotypical mucopolysaccharidosis, a new ly recognized from of inherited mucopolysaccharide storage; 3. dyserythropoietic anemia in a patient with homozygosity due to increased isolated HbA2, a Cooleg-like anemia characterized by very long survival without transfusion treatment; 4. dyserythropoietic changes prior to any treatment in the bone marrow of cases of promyelocytic, myelomonocytoid and basophilic leukemia. The cytomorphologic and serologic features of this clinical material are discussed. Particular reference is made to a new finding, i.e. phagocytosis of degenerated erythroblasts by Alder's granuloblasts, as a new form of congenital dyserythropoietic anemia. Finally, a further dyserythropoietic condition is pointed out which is related to human fetal erythropoiesis and characterized by a large number of reticuloerythroblast islets and a dyserythropoietic pattern. However, although it appears to point to ineffective erythropoiesis this last condition cannot be considered as pathologic but as a teleologic hemopoietic phenomenon.
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PMID:[Dyserythropoietic anemai]. 107 92

The clinical, hematologic, and histological characteristics of two patients who progressed from refractory anemia to acute leukemia are described. When first studied, nuclear bridging of erythroblasts, similar to that seen in congenital dyserythropoietic anemia type I and megakaryocytic dysplasia, were the only abnormalities. Within 6 years, both patients died, the first of acute nonlymphocytic leukemia, the second of erythroleukemia. Nuclear bridging of erythroblasts in the marrow of these patients was an early and transient phenomenon and was not observed during the terminal phase of leukemia.
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PMID:Nuclear bridging of erythroblasts in acquired dyserythropoiesis: an early and transient preleukemic marker. 394 11

GATA1 is mutated in patients with 2 different disorders. First, individuals with a GATA1 mutation that blocks the interaction between GATA-1 and its cofactor Friend of GATA-1 (FOG-1) suffer from dyserythropoietic anemia and thrombocytopenia. Second, children with Down syndrome who develop acute megakaryoblastic leukemia harbor mutations in GATA1 that lead to the exclusive expression of a shorter isoform named GATA-1s. To determine the effect of these patient-specific mutations on GATA-1 function, we first compared the gene expression profile between wild-type and GATA-1-deficient megakaryocytes. Next, we introduced either GATA-1s or a FOG-binding mutant (V205G) into GATA-1-deficient megakaryocytes and assessed the effect on differentiation and gene expression. Whereas GATA-1-deficient megakaryocytes failed to undergo terminal differentiation and proliferated excessively in vitro, GATA-1s-expressing cells displayed proplatelet formation and other features of terminal maturation, but continued to proliferate aberrantly. In contrast, megakaryocytes that expressed V205G GATA-1 exhibited reduced proliferation, but failed to undergo maturation. Examination of the expression of megakaryocyte-specific genes in the various rescued cells correlated with the observed phenotypic differences. These studies show that GATA-1 is required for both normal regulation of proliferation and terminal maturation of megakaryocytes, and further, that these functions can be uncoupled by mutations in GATA1.
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PMID:Differential requirements for the activation domain and FOG-interaction surface of GATA-1 in megakaryocyte gene expression and development. 1586 Jun 65

GATA family transcription factors play essential roles in broad developmental settings. GATA-1, one of the hematopoietically expressed members, is required for normal erythroid and megakaryocytic differentiation. Over the past few years, mutations in the gene encoding GATA-1 have been linked to several human hematologic disorders, including X-linked dyserythropoietic anemia and thrombocytopenia, X-linked thrombocytopenia and beta-thalassemia, and Down syndrome acute megakaryoblastic leukemia. This review summarizes the role of GATA-1 during normal hematopoiesis and discusses how disease-associated mutations may affect its function.
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PMID:GATA transcription factors in hematologic disease. 1615 17

Some familial platelet disorders are associated with predisposition to leukemia, myelodysplastic syndrome (MDS) or dyserythropoietic anemia. We identified a family with autosomal dominant thrombocytopenia, high erythrocyte mean corpuscular volume (MCV) and two occurrences of B cell-precursor acute lymphoblastic leukemia (ALL). Whole-exome sequencing identified a heterozygous single-nucleotide change in ETV6 (ets variant 6), c.641C>T, encoding a p.Pro214Leu substitution in the central domain, segregating with thrombocytopenia and elevated MCV. A screen of 23 families with similar phenotypes identified 2 with ETV6 mutations. One family also had a mutation encoding p.Pro214Leu and one individual with ALL. The other family had a c.1252A>G transition producing a p.Arg418Gly substitution in the DNA-binding domain, with alternative splicing and exon skipping. Functional characterization of these mutations showed aberrant cellular localization of mutant and endogenous ETV6, decreased transcriptional repression and altered megakaryocyte maturation. Our findings underscore a key role for ETV6 in platelet formation and leukemia predisposition.
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PMID:Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia. 2621 57