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)

Elevated levels of haemoglobin F (Hb F) have been foudn in a wide range of haematological malignancies, but very high levels were found only in juvenile chronic myeloid leukaemia (JCML), and erythroleukaemia occurring in infancy. In both these disorders a reversion to a fetal form of erythropoiesis may occur, as judged by both the structure of the Hb F and by the disappearance of Hb A2 and the carbnoic-anhydrase isozymes during the course of the illness. The clinical picture of JCML is not always associated with a reversion to fetal erythropoiesis; there appears to be a heterogeneity of conditions with this clinical label. Thus the reversion to a completely fetal pattern of erythropoiesis seems to occur in a variety of leukaemias which start in early life. This change is associated with a uniformly bad prognosis. Of a group of 17 patients with acute myeloid leukaemia 15 developed an increase in the level of Hb F about 60 days after the commencement of treatment; significantly greater increases were observed in those achieving a clinical remission. The level of Hb F usually declined during remission but high levels persisted in a few cases. Increased levels of Hb F were found also in patients with other haematological malignancies who had undergone periods of marrow aplasia during treatment. In all cases the Hb F was heterogeneously distributed throughout the red cells. Analysis of gamma15 or gammaCB3 peptides of Hb F from a variety of leukaemias gave glycine compositions ranging from 0.20 to 0.85 residues with many values in the fetal range; all cases with a reversion to fetal erythropoiesis had values in the fetal range. Attempts to confirm the 'fetal' origin of the cells containing Hb F by means of other markers was possible only in the cases of JCML and in one child with erythroleukaemia. These studies indicate that in some forms of leukaemia there may be a genuine reversion to fetal erythropoiesis while in others the emergence of cells containing Hb F appears to be part of a rapid regeneration process occurring after a period of marrow aplasia. The diagnostic and prognostic value of these observations is discussed.
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PMID:The patterns of fetal haemoglobin production in leukaemia. 81 70

Nine cases of early erythroblastic leukemia, unidentified by usual criteria, have been diagnosed using a panel of antibodies. Three cases arose in patients with Down's syndrome, one in a patient with therapy-related leukemia, and four patients were in blast crisis of chronic myeloid leukemia; only one case arose de novo. Blast cells could be assigned to two main stages of erythroid differentiation: presence of all erythroid-specific proteins in two patients, a phenotype corresponding to an immature erythroblast; absence of the erythroid markers such as glycophorin A and spectrin in the presence of carbonic anhydrase isoenzyme I, ABH group antigens, and the antigen defined by FA6 152 monoclonal antibody in six patients, a phenotype related to a late erythroid progenitor (CFU-E). One patient had an intermediate phenotype. All patients except one demonstrated a megakaryocytic component. In three patients, chromosomal abnormalities were present, detected both in blasts and in erythroid colonies. In conclusion, these findings indicate that most "cryptic erythroleukemias" are blocked at a "CFU-E-like" stage of differentiation, it may be a frequent event in Down's syndrome and chronic myeloid leukemia, and these erythroleukemias are phenotypically heterogeneous.
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PMID:Phenotype of early erythroblastic leukemias. 294 4

In silico target fishing is an emerging tool in drug discovery, which is mostly used for primary target or off-target prediction and drug repositioning. In this work, we developed an in silico target fishing protocol to identify the primary target of GV2-20, a false-positive hit highlighted in a cell-based screen for 14-3-3 modulators. Although GV2-20 does not bind to 14-3-3 proteins, it showed remarkable antiproliferative effects in CML cells, thus raising interest toward the identification of its primary target. Six potential targets of GV2-20 were prioritized in silico and tested in vitro. Our results show that the molecule is a potent inhibitor of carbonic anhydrase 2 (CA2), thus confirming the predictive capability of our protocol. Most notably, GV2-20 experienced a remarkable selectivity for CA2, CA7, CA9, and CA12, and its scaffold was never explored before as a chemotype for CA inhibition, thus becoming an interesting lead candidate for further development.
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PMID:Hit Recycling: Discovery of a Potent Carbonic Anhydrase Inhibitor by in Silico Target Fishing. 2612 9