Clinical characteristics of patients with chronic eosinophilic leukaemia (CEL) harbouring FIP1L1‐PDGFRA fusion transcript—results of Polish multicentre study

Abstract

A small subgroup of patients with hypereosinophilic syndrome (HES) demonstrates imatinib-sensitive fusion transcript-the FIP1L1-PDGFRA (F/P+). These cases are currently diagnosed as chronic eosinophilic leukaemia (CEL). In this paper, we screened 77 patients to estimate the frequency of FIP1L1-PDGFRA transcript among patients with unexplained, long-term hypereosinophilia exceeding 1.5 x 10(9)/L and to analyse the clinical and serological features in F/P+ CEL population. The FIP1L1-PDGFRA chimeric protein was detectable in 16 (14 males and 2 females) out of 77 examined HES patients (20%) by RT-PCR. Two patients suffered from cough at diagnosis. Three out of 16 (18%) patients had no organ involvements, in 5-one organ was affected and in the remaining eight cases-at least two. Eosinophilic organ damage/dysfunction identified splenomegaly in the majority of studied patients. We compared clinical and serological features between CEL F/P+ (n = 16) and HES (n = 61) patients. F/P+ cases had significantly increased WBC and absolute eosinophil count (AEC) at diagnosis (p = 0.008 and 0.02), whereas platelet count was decreased in this population (p = 0.03). Serum B12 and tryptase levels were increased (p = 0.002 and 0.004) in CEL F/P+ patients when compared to HES cases whereas serum IL-5 levels were significantly increased in the latter group (p = 0.01). Male gender and splenomegaly occurred more frequent in CEL F/P+ population (p = 0.002 and 0.0007, respectively). Additionally, patients with F/P+ CEL (n = 16) were compared with F/P- CEL (n = 8). The latter group, was significantly older, had lower AEC and higher platelet count. In conclusion, significant clinical symptoms are infrequent present and splenomegaly remains the most common organ involvement in patients with CEL expressing F/P fusion transcript. Our study confirmed the long-term remission on imatinib in this patient population.

Nilotinib and Imatinib Are Comparably Effective in Reducing Growth of Human Eosinophil Leukemia Cells in a Newly Established Xenograft Model

“…In patients suffering from CEL, relevant clinical symptoms and organ involvement vary, with splenomegaly being the only common finding [19]. Although we could show the presence of EOL-1 cells in the spleen of all mice from the placebo group (Figure 4), we did not observe pronounced splenomegaly in the animals.…”

Effect of the tyrosine kinase inhibitor nilotinib in patients with hypereosinophilic syndrome/chronic eosinophilic leukemia: analysis of the phase 2, open-label, single-arm A2101 study

“…The most frequent chromosomal abnormality is a deletion on chromosome 4q12 that creates a fusion of FIP1-like 1 protein with platelet-derived growth factor receptor α (FIP1L1- PDGFRα, or F/P) (Cools, DeAngelo et al 2003; Loules et al 2009) . F/P is present in approximately 10% to 20% of all patients with suspected nonreactive eosinophilia and is associated with increased disease severity due to constitutive tyrosine kinase activity of PDGFRα (Loules et al 2009; Helbig et al 2010; Roche-Lestienne et al 2005) . Recently, several activating mutations in PDGFRα, including Y849S, have been identified in F/P-negative patients (Elling et al 2011) .…”

Mechanisms of glucocorticoid resistance in hypereosinophilic syndromes

“…Of note, these patients have been reported to have normal serum IL-5 levels (in contrast to patients with other non-myeloid forms of HES). 33 Recent data suggests that activation of Lyn by FIP1L1-PDGFRA leads to increased phosphorylation of IL-5 receptor α promoting eosinophilopoiesis, activation and resistance to apoptosis. 34 This could explain GC resistance in this group of patients.…”