title: Association of specific cytogenetic aberrations with mdr1 gene expression in adult myeloid leukemia and its implication in treatment outcome.
abstract: OBJECTIVE
  Cytogenetics and mdr1 expression are established prognostic factors for treatment outcome in adult acute myeloid leukemia (AML). The association, however, between specific cytogenetic aberrations and mdr1 expression has not yet been examined in a large cohort of patients.
  
  
  METHODS
  We therefore looked for mdr1 gene expression at diagnosis within specific cytogenetic aberrations in 331 previously untreated adult patients with de novo or secondary AML (not including t(15;17)) entered into the German SHG AML96 treatment trial.
  
  
  RESULTS
  The proportion of mdr1 positive blast probes was significantly higher in patients with aberrant karyotypes than in those with normal karyotypes (39% vs. 15%; p<0.001). Looking at specific cytogenetic aberrations significantly more mdr1 positive AML patients were found within t(8;21), +8, +21, del(7q), del(5q), -7, abn(3q) and multiple aberrations. In contrast, no patient with inv(16) was positive for mdr1. Only 26% of mdr1 positive patients with aberrant karyotypes achieved complete remission (CR) whereas 54% of the mdr1 negative counterparts did so (p=0.002). Furthermore, within abn(11q), +21, +22, -5 or abn(3q) no mdr1 positive patient reached CR, whereas the mdr1 negative counterparts had CR rates comparable to the CR rate of patients with a normal karyotype. This was most impressive in mdr1 negative patients with multiple aberrations achieving a CR rate of 63% (p=0.019). In the multivariate analysis age, disease status and mdr1 expression were the strongest independent predictors for induction treatment failure.
  
  
  CONCLUSIONS
  The correlation described here between mdr1 gene expression and some cytogenetic aberrations might explain the prognostic divergence of such cytogenetic aberrations in different AML treatment trials due to the amount of mdr-drugs used within the protocols.
authors: Medizinische Klinik und Poliklinik I, Universitätsklinikum C.G. Carus, Fetscherstr. 74, 01307 Dresden, Germany. schaich@mk1.med.tu-dresden.de
authors: Markus
authors: M
authors: Schaich
authors: Edith
authors: E
authors: Harbich-Brutscher
authors: Ulrich
authors: U
authors: Pascheberg
authors: Brigitte
authors: B
authors: Mohr
authors: Silke
authors: S
authors: Soucek
authors: Gerhard
authors: G
authors: Ehninger
authors: Thomas
authors: T
authors: Illmer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D015331:Cohort Studies; D020732:Cytogenetic Analysis; D015870:Gene Expression; D019450:Genes, MDR / Q000502:physiology*; D006801:Humans; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis