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

A patient with subacute eosinophilic leukemia is presented, with full recognition of the controversy surrounding that entity. Serum vitamin B12 and B12-binding protein studies and simultaneous complete blood counts were done before and during 6 months of high-dose, intermittent combination chemotherapy. The patient presented with extremely high levels of serum vitamin B12, unsaturated B12-binding capacity, and transcobalamin I, all of which resembled the highest values seen in chronic myelogenous leukemia. Serial studies, during and after remission induction, showed a precipitous fall of serum vitamin B12 and unsaturated B12-binding capacity to normal levels. The data show that transcobalamin I levels, which eventually reached low-normal range, correlate best with the level of circulating and bone marrow eosinophils. Transcobalamin II and serum third binder appeared to be normal throughout the patient's course. The B12-binding protein abnormalities are not considered diagnostic of eosinophilic leukemia.
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PMID:Serum vitamin B12-binding proteins in a case of eosinophilic leukemia. 6 Jun 95

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

Epidural myeloblastoma, which compressed the spinal cord, was the first evidence for chronic granulocytic leukemia, eosinophilic type, Ph chromosome negative. This manifestation was preceded by 3 years follow-up of a patient with persistent eosinophilia of 60% mature eosinophils. The only clues for the diagnosis of leukemia were splenomegaly and high serum vitamin B12, most of which was bound to transcobalamin I. The latter finding presents a useful diagnostic criterium in myeloproliferative disorders.
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PMID:Chronic eosinophilic leukemia complicated by epidural myeloblastoma. 80 41

Elevation of transcobalamin I and serum vitamin B12 levels has usually been associated with increased granulocytic proliferation, such as occurs in chronic myelogenous leukemia. Two patients with metastatic cancer had extremely high serum vitamin B12 and transcobalamin I levels--greater than those seen in even the most intense granulocytic proliferation--that were not explainable by leukocytosis. The subjects' serum vitamin B12 levels were 18,750 and 21,221 pg per milliliter (normal, 471 plus or minus 174 pg per milliliter, mean plus or minus S.D.) and unsaturated vitamin B12 binding capacity 158,750 and 5,400 pg per milliliter (normal, 1153 plus or minus 313 pg per milliliter) respectively. The abnormally elevated serum binder was shown to be identical with transcobalamin balamin I in every respect. Levels of transcobalamin II and serum third binder were normal. The cause of the binder abnormality is unknown, but factors other than granulocyte proliferation may control or contribute to the production or accumulation of transcobalamin I.
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PMID:Extreme elevation of serum transcobalamin I in patients with metastatic cancer. 105 6

The normal human granulocyte vitamin B12-binding protein, transcobalamin I, and transcobalamin III, have been labeled with 125I-labeled N-succinimidyl 3-(4-hydroxyphenyl)propionate and utilized for plasma clearance studies performed with rabbits. Both moieties of 125I-labeled granulocyte vitamin B12-binding protein-[57Co]vitamin B12 were cleared rapidly from the plasma (is less than 90% by 5 min) by the liver. After 30 min, the bulk of the 125I reappeared in the plasma in small molecular weight (less than 1000) form and was rapidly excreted in the urine. After 60 min the bulk of the [57Co]vitamin B12 reappeared in the plasma bound to rabbit transcobalamin II and was subsequently taken up by a variety of tissues. Approximately 15% of the 125I-labeled granulocyte vitamin B12-binding protein-[57Co-a1vitamin B12 was excreted intact into the bile during the period from 10 to 80 min after injection. The hepatic uptake of the protein-vitamin B12 complex was blocked by the prior injection of desialyzed fetuin but not by native fetuin. Similar results were obtained with 125I-labeled transcobalamin III-[57Co]vitamin B12. Approximately 90% of both moieties of 125I-labeled transcobalamin I-[57Co]vitamin B12 had prolonged plasma survivals similar to that of 125I-labeled bovine serum albumin. After treatment with neuraminadase, both moieties of the 125I-labeled transcobalamin I-[57Co]vitamin B12 complex were cleared rapidly from the plasma by the liver in a manner that was indistinguishable from that observed in the case of untreated granulocyte vitamin B12-binding protein and transcobalamin III. These observations indicate that desialyzed transcobalamin I and the native forms of the granulocyte vitamin B12-binding protein and transcobalamin III are cleared from plasma by the mechanism elucidated by Ashwell and Morell (Ashwell, G., and Morell A. G. (1974) Adv. Enzymol. 41, 99-128) that is capable of clearing a wide variety of asialoglycoproteins. These observations have implications concerning the function of the human R-type vitamin B12-binding proteins, the nature of the enterohepatic circulation of vitamin B12, the biological significance of the mechanism described by Ashwell and Morell, and the etiology of the increased plasma concentration of human R-type protein that occurs frequently in chronic myelogenous leukemia and occasionally in hepatocellular carcinoma and other solid tumors.
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PMID:Human plasma R-type vitamin B12-binding proteins. II. The role of transcobalamin I, transcobalamin III, and the normal granulocyte vitamin B12-binding protein in the plasma transport of vitamin B12. 117 45

We have isolated and characterized a 2.4-kb cDNA clone encoding human neutrophil collagenase (HNC), a member of the family of matrix metalloproteinases restricted to secondary granules within neutrophils. Partial amino acid sequence was used to deduce oligonucleotide probes. These probes were used to screen a human granulocyte cDNA library derived from messenger RNA (mRNA) from a patient with chronic granulocytic leukemia. Cell-free translation of RNA produced from the cDNA produced a 52-Kd protein that was recognized by anti-HNC antibody. The cDNA clone was sequenced and shown to encode a 467-residue protein whose sequence matched those regions currently known for HNC. The enzyme exhibits 58% homology to human fibroblast collagenase and has the same domain structure. It consists of a 20-residue signal peptide, and an 80-residue propeptide that is lost on autolytic activation by cleavage of an M-L bond. Other regions identified include the autolytic degradation site, the "cysteine switch" residue that is involved in latency and activation, and a putative zinc binding sequence. HNC has six potential N-linked glycosylation sites. The cDNA hybridized to a 3.4-kb mRNA in RNA from a patient with chronic granulocytic leukemia, but not to RNA from uninduced HL60 cells or HL60 cells that had been induced to undergo granulocytic or monocytic maturation with dimethyl sulfoxide or 12-O-tetradecanoylphorbol 13-acetate, respectively. These results parallel those seen with lactoferrin and transcobalamin I, two other secondary granule proteins.
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PMID:Structure and expression of the cDNA encoding human neutrophil collagenase. 164 48

The preleukemic syndrome occurs mainly after middle age. We report 11 patients, aged 62 to 92 years, who presented with weakness, fatigue, malaise and pallor. Eight patients died; survival from the time of diagnosis was between 2 and 21 months. Two of them developed acute myelomonocytic leukemia. A third patient developed Philadelphia chromosome-negative chronic myeloid leukemia within 9 months. Serum unsaturated B12 binding capacity and transcobalamin I were elevated in this patient, preceding the transformation to chronic myeloid leukemia. Five other patients died from sepsis or pneumonia. All patients were anemic, and 10 were leukopenic. Bone marrow was hypocellular in 1 and hypercellular in 10 cases. Chromosomal studies were performed in five patients, with three showing abnormal findings: 47xx, trisomy 8 and a tetraploid karyotype 92xxyy5q-. No cytotoxic treatment should be given during the preleukemic phase until transformation to acute leukemia occurs. Since preleukemic patients are very susceptible to infections, early diagnosis of the condition is important, as is supportive care in the case of surgery.
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PMID:Preleukemic syndrome in elderly patients--report of 11 cases. 385 73

R-type vitamin B12 binding proteins (R proteins) from human granulocytes, erythrocytes, plasma, and other body fluids were characterized by isoprotein banding patterns on autoradiograms after resolution via thin-layer polyacrylamide isoelectric focusing (IEF) gel electrophoresis. R proteins obtained from various tissue sources in a given individual show tissue-specific electrophoretic patterns. The desialated R proteins obtained following in vitro treatment with neuraminidase are, however, the same for any given individual and do not show tissue specificity. The differences seen in native R proteins (i.e., transcobalamin I, III, and others) obtained from different tissues are due to variations only in the sialic acid content. Granulocytes from patients with chronic myelogenous leukemia (CML) contain both TC I and TC III, and these R proteins can be released in vitro by lithium stimulation. Normal granulocytes contain only TC III. Differences in desialated R proteins from individual to individual are due to a genetic polymorphism controlled by a single genetic locus (designated TCR) with two alleles, 1 and 2, which are found to be codominantly expressed in heterozygous individuals. The allelic variants of the desialated R proteins found in different blood cells and body fluids are controlled by only one genetic locus.
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PMID:The biochemical and genetic basis for the microheterogeneity of human R-type vitamin B12 binding proteins. 694 16

Treatment of a 74 year old patient with chronic myelogenous leukemia (CML) with busulphan resulted in an abrupt and pronounced decrease of the white blood cell (WBC) count with restoration of normal peripheral blood cell morphology and regression of splenomegaly. The Philadelphia positive (Ph+) clone was however still detectable. The alterations in the WBC count and morphology were not preceded by marrow hypoplasia but correlated closely with a marked decrease in the serum levels of Transcobalamin I (TC I), a vitamin B12-binding protein derived from immature myeloid precursors and a reciprocal rise in serum TC III, a vitamin B12-binding protein originating from terminally differentiated mature granulocytes. Studies on the HL-60 cell line showed that busulphan is capable of inducing leukemic cells to differentiate into granulocyte-like cells. These observations, taken together, suggest that in addition to its potent myelosuppressive effects, busulphan may induce apparent clinical remissions in some CML patients by promoting terminal cell differentiation.
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PMID:Induction of differentiation of myeloid leukemic cells by busulphan: in vivo and in vitro observations. 826 Sep