Recurrent finding of the FIP1L1-PDGFRA fusion gene in eosinophilia-associated acute myeloid leukemia and lymphoblastic T-cell lymphoma

• DOI: 10.1038/sj.leu.2404662
• Publication Date: 2007-03-22T08:03:17Z
• Authors: G Metzgeroth; C Walz; J Score; R Siebert; S Schnittger; C Haferlach; H Popp; T Haferlach; P Erben; J Mix; M C Müller; H Beneke; L Müller; F Del Valle; W E Aulitzky; G Wittkowsky; N Schmitz; C Schulte; K Müller-Hermelink; E Hodges; S J Whittaker; F Diecker; H Döhner; P Schuld; R Hehlmann; A Hochhaus; N C P Cross; A Reiter
• Keywords: Lymphoblastic lymphoma; Hematology; PDGFRA

The FIP1L1-PDGFRA fusion gene has been described in patients with eosinophilia-associated myeloproliferative disorders (Eos-MPD). Here, we report on seven FIP1L1-PDGFRA-positive patients who presented with acute myeloid leukemia (AML, n=5) or lymphoblastic T-cell non-Hodgkin-lymphoma (n=2) in conjunction with AML or Eos-MPD. All patients were male, the median age was 58 years (range, 40-66). AML patients were negative for common mutations of FLT3, NRAS, NPM1, KIT, MLL and JAK2; one patient revealed a splice mutation of RUNX1 exon 7. Patients were treated with imatinib (100 mg, n=5; 400 mg, n=2) either as monotherapy (n=2), as maintenance treatment after intensive chemotherapy (n=3) or in overt relapse 43 and 72 months, respectively, after primary diagnosis and treatment of FIP1L1-PDGFRA-positive disease (n=2). All patients are alive, disease-free and in complete hematologic and complete molecular remission after a median time of 20 months (range, 9-36) on imatinib. The median time to achievement of complete molecular remission was 6 months (range, 1-14). We conclude that all eosinophilia-associated hematological malignancies should be screened for the presence of the FIP1L1-PDGFRA fusion gene as they are excellent candidates for treatment with tyrosine kinase inhibitors even if they present with an aggressive phenotype such as AML.