The FLT3ITD mRNA level has a high prognostic impact in NPM1 mutated, but not in NPM1 unmutated, AML with a normal karyotype.

نویسندگان

  • Friederike Schneider
  • Eva Hoster
  • Michael Unterhalt
  • Stephanie Schneider
  • Annika Dufour
  • Tobias Benthaus
  • Gudrun Mellert
  • Evelyn Zellmeier
  • Purvi M Kakadia
  • Stefan K Bohlander
  • Michaela Feuring-Buske
  • Christian Buske
  • Jan Braess
  • Achim Heinecke
  • Maria C Sauerland
  • Wolfgang E Berdel
  • Thomas Büchner
  • Bernhard J Wörmann
  • Wolfgang Hiddemann
  • Karsten Spiekermann
چکیده

The impact of a FLT3-internal tandem duplication (FLT3ITD) on prognosis of patients with acute myeloid leukemia (AML) is dependent on the ratio of mutated to wild-type allele. In 648 normal karyotype (NK) AML patients, we found a significant independent effect of the quantitative FLT3ITD mRNA level--measured as (FLT3ITD/wtFLT3)/(FLT3ITD/wtFLT3+1)--on outcome. Moreover, this effect was clearly seen in 329 patients with a mutated NPM1 gene (NPM1+), but not in 319 patients without a NPM1 mutation (wtNPM1). In a multivariate Cox regression model, the quantitative FLT3ITD mRNA level showed an independent prognostic impact on overall survival (OS) and relapse-free survival (RFS) only in the NPM1+ subgroup (OS: hazard ratio, 5.9; [95% confidence interval [CI]: 3.1-11.2]; RFS: hazard ratio, 7.5 [95% CI: 3.4-16.5]). The FLT3ITD mRNA level contributes to relapse risk stratification and might help to guide postremission therapy in NPM1-mutated AML.

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عنوان ژورنال:
  • Blood

دوره 119 19  شماره 

صفحات  -

تاریخ انتشار 2012