Aims: Rearrangement of the platelet-derived growth factor receptor B (PDGFRB) gene defines a unique group of myeloid/lymphoid neoplasms with frequent eosinophilia and high sensitivity to tyrosine kinase inhibitors. This genetic abnormality is also rarely reported in Philadelphia-like B-cell acute lymphoblastic leukaemia/lymphoma (B-ALL). PDGFRB rearrangement was initially thought to only occur in cases with 5q31–33 rearrangement as determined with conventional cytogenetics; however, there are reported cases with cryptic rearrangements. We aim to develop a broader strategy for screening of PDGFRB rearrangements of patients with myeloid/lymphoid neoplasms. Methods and results: We performed fluorescence in-situ hybridisation (FISH) for PDGFRB rearrangement in 197 patients, including 70 with B-ALL, 10 with myeloid neoplasms with 5q31–33 rearrangements, and 117 with eosinophilia (≥0.5 × 109/l in peripheral blood or ≥5% in bone marrow), and identified PDGFRB rearrangement in four of 197 (2.0%) cases. In an attempt to identify clinicopathological and genetic features that may have a stronger association with PDGFRB rearrangement, we analysed 13 patients with confirmed PDGFRB rearrangements, including 10 with myeloid neoplasms and three with B-ALL. Among the 10 patients with myeloid neoplasms, eosinophilia was present in eight, monocytosis in two, 5q31–33 rearrangement in seven, and abnormal bone marrow morphology in all. All patients with myeloid neoplasms showed an excellent response to imatinib, including a patient in blast crisis. The three B-ALL patients presented de novo, showed no eosinophilia, had a complex karyotype including 5q31–33 rearrangement, and had clinically aggressive courses with ultimate patient demise. Conclusions: These findings suggest that a higher yield for the identification of PDGFRB rearrangement may result from an index of suspicion in patients with eosinophilia, monocytosis, bone marrow features of a myeloid neoplasm, and 5q31–33 rearrangement, and patients with Philadelphia-like B-ALL.
- PDGFRB rearrangement
- lymphoid neoplasms
- myeloid neoplasms
ASJC Scopus subject areas
- Pathology and Forensic Medicine