Role of mutation independent constitutive activation of FLT3 in juvenile myelomonocytic leukemia

Andrica C H de Vries, Ronald W Stam, Pauline Schneider, Charlotte M Niemeyer, Elisabeth R van Wering, Oskar A Haas, Christian P Kratz, Monique L den Boer, Rob Pieters, Marry M van den Heuvel-Eibrink

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

FLT3 gene mutations have been identified as prognostic factors in myeloid malignancies. Furthermore, FLT3 can be activated by wild type overexpression or ligand-dependent in leukemic cells co-expressing FLT3 ligand (FLT3L). So far no data are available on FLT3/FLT3L expression and activation in JMML. In 51 clinical JMML samples, activating mutations were screened, FLT3 and FLT3L mRNA levels were assessed and the sensitivity of JMML cells to the FLT3 inhibitor PKC412 was tested by MTT assays. No evidence for constitutively activation of FLT3/FLT3L was found in JMML, indicating that FLT3 inhibitors are unlikely to be effective in JMML.

Original languageEnglish
Pages (from-to)1557-60
Number of pages4
JournalHaematologica
Volume92
Issue number11
DOIs
Publication statusPublished - Nov 2007
Externally publishedYes

Keywords

  • Enzyme Activation
  • Enzyme Inhibitors/pharmacology
  • Humans
  • Leukemia, Myelomonocytic, Juvenile/enzymology
  • RNA, Messenger/analysis
  • Staurosporine/analogs & derivatives
  • fms-Like Tyrosine Kinase 3/antagonists & inhibitors

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