Abstract
BackgroundPrimary eosinophlia associated with the FIP1L1-PDGFRA rearrangement represents a subset of chronic eosinophilic leukaemia (CEL) and affected patients are very sensitive to imatinib treatment. This study was undertaken in order to examine the prevalence and the associated clinicopathologic and genetic features of FIP1L1-PDGFRA rearrangement in a cohort of 15 adult patients presenting with profound eosinophilia (> 1.5 × 109/L).MethodsReverse transcriptase-polymerase chain reaction (RT-PCR) was used for the detection of FIP1L1-PDGFRA rearrangement and the results confirmed by direct sequencing. C-KIT-D816V mutation was analysed retrospectively by PCR and restriction-fragment-length-polymorphism (PCR-RFLP), in all cases with primary eosinophilia.ResultsTwo male patients with splenomegaly carried the FIP1L1-PDGFRA rearrangement, whilst 2 others were ultimately classified as suffering from idiopathic hypereosinophlic syndrome (HES) and one from systemic mastocytosis. These patients were negative for the C-KIT-D816V mutation and received imatinib (100–400 mg daily). Patients with CEL and HES responded to imatinib and remained in complete haematological, clinical and molecular (for carriers of FIP1L1-PDGFRA rearrangement) remission for a median of 28.2 months (range: 11–54), whilst the patient with systemic mastocytosis did not respond. Interestingly, in both patients with FIP1L1-PDGFRA rearrangement, the breakpoints into PDGFRA were located within exon 12 and fused with exons 8 and 8a of FIP1L1, respectively.ConclusionAn early diagnosis of FIPIL1-PDGFRA-positive CEL and imatinib treatment offer to the affected patients an excellent clinical therapeutic result, avoiding undesirable morbidity. Moreover, although the molecular mechanisms underlying disease pathogenesis remain to be determined, imatinib can be effective in patients with idiopathic HES.
Highlights
Primary eosinophlia associated with the FIP1L1-PDGFRA rearrangement represents a subset of chronic eosinophilic leukaemia (CEL) and affected patients are very sensitive to imatinib treatment
The most frequent genetic aberration is the cryptic deletion of 4q12, i.e. del(4)(q12), producing the FIP1-like 1/plateletderived growth factor receptor alfa (FIP1L1-PDGFRA) fusion transcript, which results in an eosinophilic, myeloproliferative disorder [5]
Two others were classified as idiopathic hypereosinophilic syndrome (HES) and another as systemic mastocytosis, after bone marrow and lymph node biopsies, indicating mast cell infiltration
Summary
Primary eosinophlia associated with the FIP1L1-PDGFRA rearrangement represents a subset of chronic eosinophilic leukaemia (CEL) and affected patients are very sensitive to imatinib treatment. This study was undertaken in order to examine the prevalence and the associated clinicopathologic and genetic features of FIP1L1-PDGFRA rearrangement in a cohort of 15 adult patients presenting with profound eosinophilia (> 1.5 × 109/L). The most frequent genetic aberration is the cryptic deletion of 4q12, i.e. del(4)(q12), producing the FIP1-like 1/plateletderived growth factor receptor alfa (FIP1L1-PDGFRA) fusion transcript, which results in an eosinophilic, myeloproliferative disorder (chronic eosinophilic leukaemia, CEL) [5]. In a subset of patients with HES, eosinophilia is secondary to a primitive Th2 lymphoid disorder, overproducing interleukin-5 (IL-5), indicating the existence of lymphocyte-mediated HES [3]
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