title: Recurrent finding of the FIP1L1-PDGFRA fusion gene in eosinophilia-associated acute myeloid leukemia and lymphoblastic T-cell lymphoma.
abstract: 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.
authors: III. Medizinische Universitätsklinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.
authors: G
authors: G
authors: Metzgeroth
authors: C
authors: C
authors: Walz
authors: J
authors: J
authors: Score
authors: R
authors: R
authors: Siebert
authors: S
authors: S
authors: Schnittger
authors: C
authors: C
authors: Haferlach
authors: H
authors: H
authors: Popp
authors: T
authors: T
authors: Haferlach
authors: P
authors: P
authors: Erben
authors: J
authors: J
authors: Mix
authors: M C
authors: MC
authors: Müller
authors: H
authors: H
authors: Beneke
authors: L
authors: L
authors: Müller
authors: F
authors: F
authors: Del Valle
authors: W E
authors: WE
authors: Aulitzky
authors: G
authors: G
authors: Wittkowsky
authors: N
authors: N
authors: Schmitz
authors: C
authors: C
authors: Schulte
authors: K
authors: K
authors: Müller-Hermelink
authors: E
authors: E
authors: Hodges
authors: S J
authors: SJ
authors: Whittaker
authors: F
authors: F
authors: Diecker
authors: H
authors: H
authors: Döhner
authors: P
authors: P
authors: Schuld
authors: R
authors: R
authors: Hehlmann
authors: A
authors: A
authors: Hochhaus
authors: N C P
authors: NC
authors: Cross
authors: A
authors: A
authors: Reiter
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D001549:Benzamides; D018572:Disease-Free Survival; D004802:Eosinophilia / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D000068877:Imatinib Mesylate; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000188:drug therapy; D000090243:Nucleophosmin; D015514:Oncogene Proteins, Fusion / Q000032:analysis* / Q000235:genetics; D010879:Piperazines / Q000008:administration & dosage*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000008:administration & dosage*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D012074:Remission Induction / Q000379:methods; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics
chemical_list: D001549:Benzamides; C479818:FIP1L1 protein, human; C000716967:NPM1 protein, human; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D011743:Pyrimidines; D039221:mRNA Cleavage and Polyadenylation Factors; D000090243:Nucleophosmin; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D020796:Receptor, Platelet-Derived Growth Factor alpha