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. 2020 Jun;76(7):1042-1054.
doi: 10.1111/his.14097. Epub 2020 May 17.

Systematic use of fluorescence in-situ hybridisation and clinicopathological features in the screening of PDGFRB rearrangements of patients with myeloid/lymphoid neoplasms

Hong Fang  1 , Guilin Tang  1 , Sanam Loghavi  1 , Patricia Greipp  2 , Wei Wang  1 , Srdan Verstovsek  3 , L Jeffrey Medeiros  1 , Kaaren K Reichard  4 , Roberto N Miranda  1 , Sa A Wang  1
Affiliations

Systematic use of fluorescence in-situ hybridisation and clinicopathological features in the screening of PDGFRB rearrangements of patients with myeloid/lymphoid neoplasms

Hong Fang et al. Histopathology. 2020 Jun.

Abstract

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.

Keywords: PDGFRB rearrangement; lymphoid neoplasms; myeloid neoplasms.

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References

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