t(5;9)(q11;q34): a novel familial translocation involving abelson oncogene and association with hypereosinophilia

Abstract

A 6-year-old girl with hypereosinophilia was found to have a familial constitutional translocation t(5;9)(q11;q34). Flow cytometry and gene rearrangement studies did not show any clonal T-helper cell proliferation. Presence of cryptic Philadelphia translocation was ruled out by reverse transcription polymerase chain reaction. Abelson oncogene translocation on chromosome 5 was confirmed by fluorescent in situ hybridization. This is the first example of a familial translocation involving the abelson oncogene and association with hypereosinophilia. The authors discuss a novel mechanism of hypereosinophilia involving the hybrid product of the abelson oncogene with an unknown partner gene on chromosome 5 (probably granzyme-A). Hypereosinophilic syndrome comprises a heterogenous group of patients with an idiopathic, sustained elevation of the eosinophil count to more than 1,500/mm3, with subsequent signs and symptoms of organ involvement (1). Demonstration of the clonal nature of eosinophils in some patients with hypereosinophilia suggests that a myeloproliferative disorder of eosinophilic lineage is the mechanism in some instances (2,3). However, the basic pathophysiologic mechanism in a significant number of cases of idiopathic hypereosinophilia appears to be related to a clonal proliferation of T-helper cells (4). This results in the production of eosinophilopoietic cytokines such as interleukin-5, which contribute to the peripheral activation of eosinophils and promote their survival by inhibiting apoptosis (5). In many patients with hypereosinophilia, no abnormal T-cell clone is detected and the underlying pathophysiologic basis remains unexplained. We report here a case of a constitutional balanced translocation t(5;9)(q11.2;q34) involving abelson (abl) oncogene and its association with hypereosinophilia. We discuss the possible role of the translocated abl gene on 9q34 and the unknown partner gene on 5q11 in the development of eosinophilia.