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

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

A case of chronic myelogenous leukemia (CML) of 10-year survival in described. A 44-year old male was admitted to our hospital because of general malaise, abdominal fullness and fever in February, 1977. On physical examination, giant splenomegaly and hepatomegaly were detected. Peripheral blood examination revealed leukocytosis without hiatus leukemia , normochromic macrocytic anemia and thrombocytosis. NAP rate and score were 16% and 22. Cytogenetic analysis of PB without stimulator revealed 46, XY, Ph1. Then he was diagnosed as having a typical type of Ph1-positive CML. He had been successfully treated over 9 years by intermittent administration of busulfan. However, anemia suddenly progressed in February, 1986 followed by leukopenia and thrombocytopenia. Hemorrhage was not detected by the examination. Though he had been received blood transfusion, the anemia progressed rapidly. He was died of cachexia on 4th of August, 1987. The postmortem examination revealed bone marrow aplasia with no signs of blast crisis nor myelofibrosis. Secondary hemochromatosis was seen in the liver, spleen, pancreas and some other organs.
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PMID:[Bone marrow aplasia without blast crisis in a case of CML of 10-year survival]. 279 87

Syndrome of abnormal chromatin clumping in leucocytes syndrome (ACCLS) is an uncommon entity which shares clinical and biological features with the myelodysplastic (MDS) and chronic myeloproliferative syndrome. In fact, as some authors consider ACCLS a new type of MDS, others maintain that it is in Ph'negative/bcr-abl negative chronic myeloid leukaemia. A new case of ACCLS appeared in a 68 year old woman, who presented with anaemic symptoms, bleeding and recurrent infections, and a haematological picture including progressive macrocytic anemia, thrombocytopenia and leuco-erythroblastosis. Marrow hypercellularity with granulocytic hyperplasia, and mature granulocytes presenting nuclear hyposegmentation and large peripheral blocks of chromatin separated by clear zones were the characteristic features of this case. No cytogenetic abnormalities were found and DNA flow-cytometry content was normal (euploid), supporting the thought that a disequilibrium exists in the hetero-chromatin/eucromatin ration in AACLS. Reverse PCR for bcr-abl transcripts was negative. The cell-cycle-phase analysis showed a high fraction of S-cells in the bone marrow (27%) in contrast to a very low S-phase (0.2%) in the peripheral blood, pattern that is different from both CMML and CML. In vitro clonogenic assays showed a high colony forming capacity and a certain grade of autonomous proliferation of the bone marrow cells, which is reminiscent of the CMML growth behaviour in culture. The patient was treated with vitamin D3, low dose Ara-C, prednisone and hydroxyurea until her demise, fifteen months after diagnosis. In total, the patient received 47 units of packed cells and 114 of platelet concentrates, and was transfused only when she presented anaemic or hemorrhagic symptoms. These clinical and haematological features suggest that ACCLS is a distinct entity that should be considered a sixth type of MDS, beside CMML, with which it has much in common.
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PMID:[Syndrome of abnormal chromatin clumping in leucocytes with a high fraction of bone marrow cells in S-phase and in vitro autonomous growth]. 937 66

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

Imatinib-induced macrocytic anemia was known to result from c-kit inhibition in chronic myeloid leukemia (CML). However, recent studies showed that the prevalence of anemia is increased with high trough imatinib level and increased doses of imatinib influence decreased proliferation of burst forming units-erythroids (BFU-Es). The aim of this study was to evaluate the continuously increased mean cell volume (MCV) level's correlation with cytogenetic response and the favorable outcome in early chronic phase (CP)-CML patients. Clinical importance of MCV level was evaluated to correlate with cytogenetic response and compared with Sokal score, a known excellent prognostic parameter of cytogenetic response (CCR) in 84 early CP-CML patients. The patients with early and continuously increased MCV level irrespective of anemia achieved higher CCR after 12 months of imatinib therapy than patients with non-CCR (p=0.011). When the value was compared with low Sokal score, elevated MCV was independent predictor of CCR (RR=12.925, p=0.002 vs. RR=35.445, p<0.001). Furthermore, the patients with early and continuously increased MCV level had a higher probability of maintaining CCR than non-increased level (p=0.019). Increased MCV level was surrogate marker of achievement and durability to CCR for early CP-CML patients in the present study.
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PMID:Mean cell volume can be an early predictor for the cytogenetic response of chronic myeloid leukemia patients treated with imatinib? 1961 45