FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosinophilia

Abstract

A novel oncogenic mutation (FIP1L1-PDGFRA), which results in a constitutively activated platelet-derived growth factor receptor-␣ (PDGFRA), has been invariably associated with a primary eosinophilic disorder. The current study examines both the prevalence and the associated clinicopathologic features of this mutation in a cohort of 89 adult patients presenting with an absolute eosinophil count (AEC) of higher than 1.5 ؋ 10 9 /L. A fluorescence in situ hybridization (FISH)-based strategy was used to detect FIP1L1-PDGFRA in bone marrow cells.

Five years since the discovery of FIP1L1–PDGFRA: what we have learned about the fusion and other molecularly defined eosinophilias

“…10 In a Mayo series, 11 of 89 patients (12%) with moderateto-severe eosinophilia were FIP1L1-PDGFRA positive. 11 In a follow-up series of 714 unselected patients with eosinophilia, only 3% were fusion positive. 12 Additional studies are listed in Table 2.…”

“…69 Histopathologically, the bone marrows of patients with FIP1L1-PDGFRA-positive SM-Eo exhibit less dense clusters of mast cells by tryptase immunostaining than are typically seen in SM, particularly cases with the common D816V KIT mutation. 11 However, in some cases of CEL with increased bone marrow mast cells, the mast cells may exhibit spindle-shaped morphology, form multifocal clusters and aberrant surface expression of CD25, major and minor criteria, which establish the basis for a WHO diagnosis of SM. Such cases may be considered a hybrid category of SM-CEL, wherein the CEL component is the associated hematologic non-mast cell lineage disease, pathogenetically driven by FIP1L1-PDGFRA.…”

How I treat hypereosinophilic syndromes

“…16 Unfortunately, many patients show only a transient or partial response and require treatment with additional agents. Although reported imatinib response rates in PDGFRA-negative HES vary widely (9-60%) depending on the series, 16,[78][79][80] recent data from our center suggest that the presence of myeloproliferative features (presumed clonal eosinophilic involvement) is an important predictor of imatinib response in patients with FIP1L1-PDGFRA-negative HES. Of note, PDGFR-negative patients often require higher doses of imatinib and appear to respond more slowly.…”

WT1 transcript amount discriminates secondary or reactive eosinophilia from idiopathic hypereosinophilic syndrome or chronic eosinophilic leukemia

“…This hybrid transcript represents not only a molecular marker of HES but it offers the basis for a molecular targeted therapy with imatinib. [9][10][11][12][13] In spite of this, in most patients with eosinophilia, no molecular lesions can be detected and the majority of them exhibit a normal karyotype by conventional cytogenetic, with only sporadic cases with clonal chromosomal abnormalities. 14 So far, for the majority of them, the diagnosis of HES is based on exclusion criteria 15 and in same cases it may remain doubt.…”