Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The thrombocytic beta-thromboglobulin (beta-TG) level--a specific globulin secreted by the alpha-granules--is an important criterion in the contemporary diagnosis of acquired thrombocytopathies. The beta-TG was determined by the radioimmunologic test of the firm "Amersham" in thrombocytic lysates and thrombocyte-poor plasma of 54 persons: 24 patients with acute leukemia, 14 patients with chronic myeloid leukemia and 15 healthy controls. The leukemic patients were with a preliminary proved thrombocytopathy type "empty thrombocytic pool disease" which had been proved via aggregation measurement by the ATP and ADP levels in the thrombocytes and by the thrombocytic factor 4 level. While the intraplatelet beta-TG concentration in acute leukemia and chronic myeloid leukemia was found unchanged, in the patients with acute leukemia its secretion in the plasma was decreased (154.71 + 16.77 ng/10(5) platelets). The data interpretation shows that in these malignant hemopathies the alpha-granules do not take part in the "empty pool disease". In acute leukemia the pathogenesis of the thrombocytopathy is determined by the so-called "thrombocytic secretion paresis" which is confirmed by the thrombocytic factor 4 low level.
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PMID:[The thrombocytic beta-thromboglobulin level of patients with blastic leukemia and chronic myeloleukemia]. 297 86

Acute leukemia (AL) is a relatively uncommon, but dreaded, complication occurring with increased frequency in individuals with Down syndrome (DS). This selective update includes aspects of AL in DS in which a change or advancement in our understanding of this disease has occurred. Despite previous reports describing a worse outcome for these individuals, more recent studies have suggested an improved response to current treatment strategies (including high-dose AraC) equaling, or even surpassing, the survival of non-DS individuals with AL. An increased toxicity to methotrexate in DS patients has also been recognized. While the leukemia of DS infants has been described as megakaryoblastic, the spectrum of in vitro differentiation is much broader including (in addition to megakaryocytic colonies) various myeloid, macrophage, and even erythroid colonies. Although the cause(s) of DS-AL remains unknown, potential candidate genes include those encoded on chromosome 21 that play a role in other defined leukemias in non-DS individuals. The AML1/PEBP2alpha gene maps to the DS critical region and is characteristically associated with two leukemia-associated chromosomal translocations: 1) the 8;21 translocation involving an AML1/ETO fusion transcript commonly seen in acute myelogenous leukemia (AML) and; 2) a 3;21 translocation identified in certain chemotherapy-related myelodysplasias/leukemias and occasionally in the blast crisis of chronic myelogenous leukemia cells. Similarly, the ETS-related gene, ERG, involved in the AML 16;21 maps to the q22 region of chromosome 21. Lastly, a familial platelet disorder with a propensity to develop myeloid leukemia has been linked to 21q22.1-22.2 and conceivably might involve AML1, ERG or yet another gene.
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PMID:Down syndrome and leukemia, an update. 854 49

Monoallelic RUNX1 mutations cause familial platelet disorder with predisposition for acute myelogenous leukemia (FPD/AML). Sporadic mono- and biallelic mutations are found at high frequencies in AML M0, in radiation-associated and therapy-related myelodysplastic syndrome and AML, and in isolated cases of AML M2, M5a, M3 relapse, and chronic myelogenous leukemia in blast phase. Mutations in RUNX2 cause the inherited skeletal disorder cleidocranial dysplasia (CCD). Most hematopoietic missense mutations in Runx1 involve DNA-contacting residues in the Runt domain, whereas the majority of CCD mutations in Runx2 are predicted to impair CBFbeta binding or the Runt domain structure. We introduced different classes of missense mutations into Runx1 and characterized their effects on DNA and CBFbeta binding by the Runt domain, and on Runx1 function in vivo. Mutations involving DNA-contacting residues severely inactivate Runx1 function, whereas mutations that affect CBFbeta binding but not DNA binding result in hypomorphic alleles. We conclude that hypomorphic RUNX2 alleles can cause CCD, whereas hematopoietic disease requires more severely inactivating RUNX1 mutations.
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PMID:Disease mutations in RUNX1 and RUNX2 create nonfunctional, dominant-negative, or hypomorphic alleles. 1729 Feb 19