title: FAB M4 and high CD14 surface expression is associated with high cellular resistance to Ara-C and daunorubicin: implications for clinical outcome in acute myeloid leukaemia.
abstract: In 145 adult patients diagnosed with non-M3 acute myeloid leukaemia (AML) the relevance of FAB-subtype and immunophenotype to in vitro cellular drug resistance towards the anthracyclines aclarubicin (Acla) and daunorubicin (Dau), and the nucleoside analogue cytarabine (Ara-C), as well as other antileukaemic drugs, was investigated using a 4-d MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay. We demonstrate that high CD14 expression is highly significantly associated with high cellular Ara-C and Dau resistance in univariate as well as multivariate analyses. FAB subtypes with highest and lowest cellular Ara-C resistance were M4 and M5, respectively (P < 0.01, one-way anova), whereas FAB subtypes with highest and lowest cellular Dau resistance were M4 and M1, respectively (P < 0.01, one-way anova). By contrast, no significant differences in cellular drug resistance towards Acla could be demonstrated among FAB subtypes. Furthermore, in two cohorts of AML patients treated by two different regimens for remission induction over a period of 15 yr (1985-94, n = 159 and 1995-99, n = 76, respectively) we demonstrate in univariate analyses a significance of CD14 expression with respect to clinical outcome. With the exception of significance to probability of obtaining complete remission in the first cohort (P = 0.03, logistic regression), this significance was, however, lost in multivariate analyses. It was demonstrated that FAB-M4 patients were older than M5 patients and that high CD14 expression was associated with the presence of secondary AML and older age. We conclude that although cases with high blast cell CD14 expression (and FAB-M4 cases) were more resistant to Ara-C as well as Dau in vitro, the clinical and biological significance of this may be debatable because of interactions with major prognostic factors in AML.
authors.affiliation: Department of Haematology, Aarhus University Hospital, Aarhus, Denmark. janmaxgaard@dadlnet.dk
authors.forename: J M
authors.initials: JM
authors.lastname: Nørgaard
authors.forename: L H
authors.initials: LH
authors.lastname: Olesen
authors.forename: G
authors.initials: G
authors.lastname: Olesen
authors.forename: K
authors.initials: K
authors.lastname: Meyer
authors.forename: J S
authors.initials: JS
authors.lastname: Kristensen
authors.forename: K
authors.initials: K
authors.lastname: Bendix
authors.forename: B
authors.initials: B
authors.lastname: Pedersen
authors.forename: E
authors.initials: E
authors.lastname: Kjeldsen
authors.forename: P
authors.initials: P
authors.lastname: Hokland
mesh_terms: D015250:Aclarubicin / Q000008:administration & dosage / Q000494:pharmacology; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000677:Amsacrine / Q000008:administration & dosage / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000032:analysis*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002869:Chromosome Aberrations; D015331:Cohort Studies; D003561:Cytarabine / Q000008:administration & dosage / Q000494:pharmacology*; D003630:Daunorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000145:classification / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology; D015479:Leukemia, Myelomonocytic, Acute / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000494:pharmacology; D015999:Multivariate Analysis; D014411:Neoplastic Stem Cells / Q000737:chemistry*; D013866:Thioguanine / Q000008:administration & dosage / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D018950:Lipopolysaccharide Receptors; D000677:Amsacrine; D003561:Cytarabine; D005047:Etoposide; D015250:Aclarubicin; D004317:Doxorubicin; D008942:Mitoxantrone; D013866:Thioguanine; D015255:Idarubicin; D003630:Daunorubicin