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)

The utility of the enzymatic radiochemical assay of histamine in diagnosing diseases with known abnormalities in histamine production was investigated. Whole blood histamine levels were abnormal only in patients with basophilia, i.e. chronic myelocytic leukemia or polycythemia vera. Histamine was not detectable (less than 1 ng/ml) in normal plasma but was detected in plasma of some patients witheither mastocytosis or chronic myelocytic leukemia. These patients also had symptoms which could be attributed to histamine release as, for example, hyperchlorhydria and hypotension. Urinary histamine excretion was also abnormally high in these diseases compared to normal subjects (range less than 5-42 microgram/24 h, n = 31). Patients with systemic mastocytosis had higher urine values (greater than 150 microgram/24 h) than those with cutaneous mastocytosis (39-88 microgram/24 h), and the urinary histamine excretion appeared to be an index of the severity of the diseases. Studies with L-histidine loading suggest that the kidney is one possible source of urinary histamine.
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PMID:Blood and urine histamine levels in normal and pathological states as measured by a radiochemical assay. 89 Sep 80

Histamine metabolism was studied in 35 patients with polycythaemia vera (PV) at different stages of their disease and compared with controls and patients with secondary polycythaemia. In addition to blood and urinary histamine the main urinary metabolites of histamine, methylhistamine (MeHi) and 1-methyl-4-imidazoleacetic acid (MeImAA) were measured. In patients with active PV the excretion of MeHi and MeImAA was significantly higher than in controls and secondary polycythaemia, indicating an increased histamine formation. The MeImAA excretion was correlated to the blood histamine level, the degree of blood basophilia, the total white blood count and the spleen volume. The blood histamine level was significantly higher in PV patients compared with controls and secondary polycythaemia. No patients with secondary polycythaemia had an increased blood histamine level. With the bio-assay technique used in this study the urinary excretion of histamine in the PV patients was within the normal range. There was no correlation between the increased histamine formation and "histamine-related symptoms". Pruritus and duodenal ulcer occurred with a similar frequency in patients with and without increased MeImAA excretion. The similarity between the disturbance of the histamine metabolism in PV and that found by other authors in chronic myeloid leukaemia is pointed out.
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PMID:Histamine metabolism in polycythaemia vera. 117 64

Semisolid (methylcellulose) hemopoietic cultures revealed the presence of histamine-containing granulocyte colonies derived from precursors (CFU-C) present in human peripheral blood. Light microscopy and histochemical studies of cells in individual histamine-containing colonies demonstrated homogeneous populations of metachromatic basophil/mast cells (BMC) at various stages of maturation. By inverted microscopy, pure BMC colonies were more often found to have the overall appearance of the previously described "eosinophil" (type II), rather than "neutrophil-macrophage" (type I), colony type. Histamine-positive colonies constituted 58% (50/86) of all (type I and type II) granulocyte colonies in repeated cultures from a patient with systemic mastocytosis (SM), and 19% (13/67) of colonies in cultures from 8 patients with chronic myeloid leukemia (CML); this was in contrast to 8% (12/153) of colonies in cultures from 4 patients with urticaria pigmentosa (UP) and 6 normal controls (p less than 0.0001). Calculated frequency of BMC CFU-C was approximately 1 per 2 X 10(6) in normal and 1 per 2 X 10(5) nucleated cells in SM peripheral blood. Taking colony size into account, histamine content per cell in histamine-positive type II colonies in SM cultures was 1.1 +/- 0.19 pg, compared to 0.29 +/- 0.08 pg in CML and less than or equal to 0.10 in normals and UP. Electron microscopy (EM) of individual colonies revealed electron-dense granules with ultrastructural features of BMC in histamine-positive, but not histamine-negative, colonies. Use of these methods may help to further clarify the nature of BMC precursors and the regulation of their proliferation in bone marrow disorders and allergic states.
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PMID:Basophil/mast cell precursors in human peripheral blood. 657 35

Basophil numbers are typically elevated in chronic myeloid leukemia (CML) and increase during disease progression. Histamine is an essential mediator and marker of basophils and is highly up-regulated in CML. We examined the biochemical basis of histamine synthesis in CML cells. The CML-specific oncoprotein BCR/ABL was found to promote expression of histidine decarboxylase (HDC) and synthesis of histamine in Ba/F3 cells. Moreover, the BCR/ABL tyrosine kinase inhibitors imatinib (STI571) and nilotinib (AMN107) decreased histamine levels and HDC mRNA expression in BCR/ABL-transformed Ba/F3 cells, in the CML-derived basophil cell line KU812, and in primary CML cells. Synthesis of histamine was found to be restricted to the basophil compartment of the CML clone and to depend on signaling through the PI3-kinase pathway. CML cells also expressed histamine receptors (HRs), including HR-1, HR-2, HR-4, and histamine-binding CYP450 isoenzymes which also serve as targets of HR antagonists. The HR-1 antagonists loratadine and terfenadine, which bind to CYP450, were found to counteract proliferation of CML cells, whereas no growth inhibition was observed with the HR-1 antagonist fexofenadine which is not targeted or metabolized by CYP450. Moreover, DPPE, an inhibitor of histamine-binding CYP450 isoenzymes, produced growth inhibition in CML cells. Together, these data show that BCR/ABL promotes histamine production in CML cells and that certain HR-targeting drugs exert antileukemic effects on CML cells.
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PMID:The CML-related oncoprotein BCR/ABL induces expression of histidine decarboxylase (HDC) and the synthesis of histamine in leukemic cells. 1684 47