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)

Because of recent developments in the study of vitamin B12-binding proteins, the levels of the three serum binders were compared in serum and plasma samples from subjects with various disorders. The results allow the following conclusions: (1) As previously reported, transcobalamin (TC) III and to a lesser extent TC I are artifactually elevated in serum. The appear to be released in vitro during the clotting process, presumably from granulocytes. (2) Blood cells of patients with polycythemia vera release exceedingly large amounts of TC I and TC III in vitro. (3) The above findings support, but do not prove, at least a partial granulocytic source of TC I. Nevertheless, factors other than granulocytes influence TC I levels, as disorders characterized by increased TC I (most prominently chronic myelogenous leukemia but also several cases of cancer) manifest relatively little cellular release of TC I in vitro. (4) Despite the serum artifact, the serum abnormalities described in various conditions were seen in plasma also, even though the actual values of themselves were lower in plasma. The chief exception was TC III, which was elevated in plasma only in polycythemia vera (and in a few cases of leukocytosis). (5) EDTA-NaF anticoagulant is not suitable, as it causes plasma dilution, thus explaining previous reports of TC II level differences between serum and plasma. EDTA is therefore a preferable anticoagulant for vitamin B12-binding protein studies, although it too may not be ideal.
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PMID:Vitamin B12-binding proteins in serum and plasma in various disorders. Effect of anticoagulants. 41 9

Serum vitamin B12 and vitamin B12 binding proteins (transcobalamins, TCS) were determined in patients with malaria, amoebic liver abscess, carcinoma of the liver, infectious hepatitis, cirrhosis and chronic myelocytic leukemia (CML) as well as in 60 blood donor subjects. Serum vitamin B12 in patients with infectious hepatitis, cirrhosis and CML were higher than that of the normal subjects. The values of unsaturated vitamin B12 binding capacity (UBBC) in patients with carcinoma of the liver, infectious hepatitis, cirrhosis were lower while that of patients with CML were higher than that of the normal subjects. A markedly increased TCI and decreased TCII was observed in patients with CML while these changes was much less in patients with other liver diseases. The difference was possibly due to a flooding of vitamin B12 from damaged liver cells into the circulation and the decreased synthesis of transcobalamins in patients with liver diseases while the increased granulocytes, the source of TCI, was much increased in patients with CML.
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PMID:Vitamin B12 and vitamin B12 binding proteins in liver diseases. 60 23

The technique described in the preceding paper was applied to 12 abnormal sera selected for their increase in one or more B12-binding proteins. Even in the presence of large amounts of R-type binder, the ammonium sulfate technique gave a reliable separation of R binding proteins from TC II. Measurement of the TC II in abnormal sera gave results identical to those obtained by the more standard gel filtration. The R binders of four subjects with myeloproliferative disease were further separated into alpha2-R and alpha1-R. The pattern of B12 binding of polycythemia vera (PV) was an exaggeration of the normal pattern. Binding to alpha2-R was three to four times that to alpha1-R, although the total amounts bound to both were increased. In chronic myelogenous leukemia (CML), both alpha2-R and alpha1-R were also increased, but in contrast to binding in normal sera, alpha1-R predominated. In order to interpret the findings, either whole serum R or alpha1-R and alpha2-R from patients with myeloproliferative disease were subject to isoelectric focusing. Alpha2-R consisted pricipally of components isoelectric at pH 2.9, 3.0, and 3.1. These components were present in only minor amounts in normal serum and were somewhat increased in the serum of PV. These components were very much increased in the serum of CML and predominated. Alpha2-R consisted of those components isoelectric at pH 3.4,3.6, and 4.0. These components predominated in the unsaturated binding capacity of normal sera and that of PV. It was concluded that the division of plasma R binders into alpha1-R and alpha1-R by the technique described provided information useful in the study of myeloproliferative diseases.
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PMID:Measurement of vitamin B12-binding proteins of plasma. II. Interpretation of patterns in disease. 105 10

Deletion and mutagenesis of the 5'-flanking region of the human transcobalamin II (TC II) transfected in human intestinal epithelial Caco-2 cells have revealed that TC II promoter activity is: (a) very weak; (b) restricted to a core region (-29 to -163) that contained multiple transcription initiation sites; (c) not dependent on other potential elements, such as a distally localized CCAAT box, a CF1, a HIP1 binding motif and a MED-1 element; (d) modulated weakly by a positive-acting GC box (-568-GAGGCGGTGC) and strongly by a proximal GC/GT overlapping box (-179 CCCCCGCCCCACCCC). Gel shift and immunosupershift analyses demonstrated that both the positive-acting GC box and the negative-acting GC/GT box were recognized by Sp1 and Sp3. Co-transfection studies using Sp1 and/or Sp3 expression plasmids revealed that while Sp1 stimulated, Sp3 repressed Sp1-mediated transactivation of TC II transcription. The proximal GC/GT box also acted as a negative element in human chronic myelogenous leukemia K-562 and HeLa cells. These results suggest that tissue/cell specific expression of the TC II gene may be controlled by the relative ratios of Sp1 and Sp3 that bind to the GC/GT box and the weak promoter activity of TC II is due to the transcriptional repression caused by the binding of Sp3 to the proximal GC/GT box.
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PMID:Characterization of the human transcobalamin II promoter. A proximal GC/GT box is a dominant negative element. 963 63