Document Detail


Novel enzymatic abnormalities in AML and CML in blast crisis: elevated leucocyte leukotriene C4 synthase activity paralleled by deficient leukotriene biosynthesis from endogenous substrate.
MedLine Citation:
PMID:  9674747     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Leukotrienes (LT) are inflammatory mediators which can also exert regulatory effects on human myelopoiesis. We have studied the LT-producing capacity of freshly isolated leucocyte suspensions (containing blast cells in variable proportions) from 41 patients with acute myeloid leukaemia (AML) or chronic myeloid leukaemia (CML) in blast crisis (CMLbc) at diagnosis or relapse/resistant disease. Leucocyte suspensions from 19/29 AML patients (66%), and 2/12 CMLbc patients (17%; P = 0.012) demonstrated deficient capacity to synthesize LT from endogenous substrate after ionophore A23187 stimulation. Thus, these cells produced < 8 pmol LTB4+LTC4/10(6) cells (< 20% of mean LT formation in leucocyte suspensions from 18 healthy subjects). Addition of exogenous arachidonic acid did not normalize the LT synthesis in poor-producing cell suspensions. Purified, morphologically mature granulocytes from two AML patients also failed to produce normal amounts of LT. In leucocyte suspensions from the remaining 20 AML/CMLbc patients A23187 provoked LT biosynthesis, with markedly increased production of LTC4, but decreased LTB4 formation. Furthermore, elevated conversion of exogenous LTA4 to LTC4 was noted in the patient samples, independent of their capacity to produce LT after A23187 stimulation. The percentage of blast cells in patient white blood cell differential counts correlated inversely with ionophore-induced LT synthesis, but positively with the conversion of exogenous LTA4 to LTC4. The results suggest elevated LTC4 synthase activity and suppressed 5-lipoxygenase activity as novel enzymatic features of myeloid leukaemia patients with immature phenotype.
Authors:
L Stenke; M Sjölinder; T D Miale; J A Lindgren
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of haematology     Volume:  101     ISSN:  0007-1048     ISO Abbreviation:  Br. J. Haematol.     Publication Date:  1998 Jun 
Date Detail:
Created Date:  1998-08-05     Completed Date:  1998-08-05     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0372544     Medline TA:  Br J Haematol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  728-36     Citation Subset:  IM    
Affiliation:
Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Adolescent
Adult
Aged
Blast Crisis / enzymology*
Female
Glutathione Transferase / metabolism*
Granulocytes / enzymology
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / enzymology
Leukemia, Myeloid / enzymology*
Leukocytes / enzymology*
Leukotriene A4 / biosynthesis,  deficiency
Leukotriene C4 / biosynthesis,  deficiency
Leukotrienes / biosynthesis*,  deficiency
Male
Middle Aged
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Leukotriene A4; 0/Leukotrienes; 72025-60-6/Leukotriene C4; EC 2.5.1.18/Glutathione Transferase; EC 4.4.1.20/leukotriene-C4 synthase

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