A novel fusion gene involving PDGFRB and GCC2 in a chronic eosinophilic leukemia patient harboring t(2;5)(q37;q31) - PubMed (original) (raw)

Case Reports

A novel fusion gene involving PDGFRB and GCC2 in a chronic eosinophilic leukemia patient harboring t(2;5)(q37;q31)

Noriyoshi Iriyama et al. Mol Genet Genomic Med. 2019 Apr.

Abstract

Background: Platelet-derived growth factor receptor beta (PDGFRB) rearrangement has been reported in a number of patients with chronic eosinophilic leukemia (CEL), B-acute lymphoblastic leukemia, myeloproliferative neoplasms, and juvenile myelomonocytic leukemia. Here, we report a case of CEL carrying a novel fusion gene involving PDGFRB and GRIP and coiled-coil domain containing 2 (GCC2).

Patient and methods: A 54-year-old man presenting with a cough and dyspnea was diagnosed with acute eosinophilic pneumonia. Cytogenetic analysis of the bone marrow revealed the presence of t(2;5)(q37;q31). Fluorescence in situ hybridization analysis in the peripheral blood leukocytes revealed the presence of a split signal at PDGFRB gene. Imatinib treatment was effective, and disappearance of t(2;5)(q37;q31) in the bone marrow was confirmed after three months of imatinib therapy. Whole-genome sequencing was performed in peripheral blood leukocytes collected before imatinib therapy.

Results: A novel fusion gene between exon 22 of GCC2 and exon 12 of PDGFRB was detected and the presence of GCC2-PDGFRB was confirmed by PCR.

Conclusion: This is the first case report demonstrating the GCC2 gene as a partner of PDGFRB in the pathogenesis of CEL.

Keywords: GCC2; PDGFRB; chronic eosinophilic leukemia; imatinib.

© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

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Conflict of interest statement

N.I. and Y.H. received honoraria and speaker fees from Novartis Pharma K.K. The remaining coauthors declare no competing financial interests.

Figures

Figure 1

Figure 1

Computed tomography scanning showing the development of acute eosinophilic pneumonia (a). Morphology of bone marrow examination before imatinib therapy stained with May‐Giemsa (b). Cytogenetic analysis of bone marrow sample showing translocation between chromosomes 2q37 and 5q31 (c). This abnormality was observed in 16 of 20 metaphases. Fluorescence in situ hybridization of peripheral blood showing the presence of a split signal on platelet‐derived growth factor receptor beta (PDGFRB) gene (d). This was observed in 61% of nucleated cells

Figure 2

Figure 2

Clinical course of the patient after the incidence of acute eosinophilic leukemia. Low‐dose prednisone was initially administered, and it was effective for improving pneumonia but not in reducing the number of increased eosinophils. Imatinib administration rapidly reduced the number of eosinophils and the probability of cells harboring platelet‐derived growth factor receptor beta (PDGFRB) translocation in the peripheral blood. The probability of cells harboring PDGFRB translocation was evaluated by fluorescence in situ hybridization (FISH)

Figure 3

Figure 3

Whole‐genome sequence identifying the breakpoint forming platelet‐derived growth factor receptor beta (PDGFRB) and GRIP and coiled‐coil domain containing 2 (GCC2) fusion gene (a). A novel fusion gene between exon 22 of GCC2 and exon 12 of PDGFRB was detected. Direct sequencing analysis confirming the presence of GCC2‐PDGFRB fusion gene (b)

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