Myeloid and Lymphoid Neoplasms with Eosinophilia and Abnormalities of PDGFRA, PDGFRB, FGFR1, or t(8;9)(p22;p24.1);PCM1-JAK2

Abstract

Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1 were first recognized by the WHO in the 2008 edition. In the 2016 WHO, myeloid and lymphoid neoplasms with eosinophilia and t(8;9)(p22;p24.1);PCM1-JAK2 will be recognized as a provisional entity. These neoplasms more commonly affect men and occur in a broad age range, but with a median age of forties to fifties. They represent a heterogeneous group of neoplasms in which eosinophilia is typical but not required. Patients with abnormalities of PDGFRA usually present with features of chronic eosinophilic leukemia. Patients with abnormalities of PDGFRB often present with features of chronic myelomonocytic leukemia with eosinophilia, whereas patients with abnormalities of FGFR1 or t(8;9)(p22;p24.1); PCM1-JAK2 can have a more heterogeneous presentation. Conventional karyotyping can detect most of the aforementioned abnormalities; however, abnormalities of PDGFRA are often the result of a cryptic 4q12 deletion, requiring FISH analysis. Given the relative rarity of these neoplasms, PCR analysis is not available at routine laboratories, but has been proven successful in monitoring molecular disease in patients with known fusion partners. The recognition of these neoplasms is vital as patients with abnormalities of PDGFRA and PDGFRB are exquisitely sensitive to imatinib. Furthermore, JAK2 inhibitors are likely to play a substantial role in patients with t(8;9)(p22;p24.1); PCM1-JAK2. Unfortunately, effective targeted therapy has not been discovered for patients with abnormalities of FGFR1 to date. This chapter will further divulge additional details regarding this heterogeneous group of neoplasms including description of various fusion partners with PDGFRA, PDGFRB, and FGFR1.