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)

The metabolism of arachidonic acid through the lipoxygenase pathway was studied in suspensions of fresh human bone marrow cells from eight patients with chronic myelocytic leukemia (CML) and 10 normal controls. After the cells were incubated with the calcium ionophore A23187 and arachidonic acid, a technique including reverse- and straight-phase high-pressure liquid chromatography (HPLC) was employed to isolate and detect different lipoxygenase-mediated compounds. The detected compounds included leukotriene B4 (LTB4), with its two major nonenzymatic isomers 6-trans-LTB4 and 12-epi-6-trans-LTB4 5S,12S-DHETE, and the monohydroxy eicosatetraenoic acids 5-HETE, 12-HETE, and 15-HETE. The pattern of lipoxygenase-mediated products from the bone marrows was similar to that previously described from human peripheral blood. Of eight bone marrow samples from CML patients, five expressed values above 600 ng LTB4/10(8) nucleated cells, as compared to only one out of 10 controls. In contrast, the CML patients produced significantly lower amounts of both the double-dioxygenation product 5S,12S-DHETE (56.8 +/- 16.0 ng [mean +/- SE] versus 146.1 +/- 31.3 ng; p less than 0.05) and the monohydroxy acid 12-HETE (965 +/- 351 ng versus 4390 +/- 1801 ng; p less than 0.05), indicating a 12-lipoxygenase deficiency. The present results show that leukotrienes are formed by human bone marrow cells and further suggest the existence of altered lipoxygenase activity in CML.
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PMID:Leukotriene production by fresh human bone marrow cells: evidence of altered lipoxygenase activity in chronic myelocytic leukemia. 302 51

The arachidonate metabolism by leukocytes and platelets was studied in 14 patients with myeloproliferative disorders including 7 patients with chronic myeloid leukemia (CML), 5 with polycythemia vera (PV) and 2 with essential thrombocythemia (ET). When the leukocytes were incubated with arachidonate and A23187, leukotriene B4 and hydroxyeicosatetraenoic acids (HETEs) were constantly detected using reversed-phase high-performance liquid chromatography in normal subjects, while selective deficiency of 5-lipoxygenase products (leukotriene B4 and 5-HETE) was found in 4 patients with CML. this novel abnormality of the leukocytes seemed to be derived from the possible deficiency of 5-lipoxygenase in these patients' polymorphonuclear neutrophils (PMNNs). The formation of 15-HETE appeared to be almost normal in all the patients. Platelet 12-lipoxygenase deficiency was detected in 2 patients with PV and 2 with CML in whom one was associated with the deficiency of 5-lipoxygenase products. These bicellular abnormalities of the arachidonate metabolism might contribute to understand dysfunctions of PMNNs and platelets in some patients with myeloproliferative disorders.
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PMID:Altered arachidonate metabolism by leukocytes and platelets in myeloproliferative disorders. 631 27