Zimmermann Nives, Nassiri Mehdi, Zhou Jiehao, Miller Adam M, Zhang Shanxiang
Division of Hematopathology, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 W 11(th) St, Indianapolis, IN 46202, USA; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
Division of Hematopathology, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 W 11(th) St, Indianapolis, IN 46202, USA.
Cancer Genet. 2020 Jun;244:55-59. doi: 10.1016/j.cancergen.2020.03.002. Epub 2020 May 3.
Rearrangements of PDGFRB are defining cytogenetic abnormalities seen in "Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRB" and are generally evident by common cytogenetic methods. Here we present an unique case in which karyotyping and fluorescence in situ hybridization (FISH) analysis were negative, and the PDGFRB rearrangement was detected by next-generation sequencing (NGS) analysis. The patient presented with approximately one-year history of leukocytosis including neutrophilia, eosinophilia, basophilia and granulocytic left shift. Bone marrow biopsy revealed a hypercellular marrow with panmyelosis, eosinophilia and mast cell hyperplasia. Blasts were not increased. Ancillary studies revealed a normal karyotype and absence of BCR-ABL1 fusion gene. NGS identified AFAP1L1-PDGFRB fusion, which was confirmed by polymerase chain reaction amplification followed by direct Sanger sequencing. The patient was treated with imatinib and showed normalization of peripheral blood leukocytosis, which lasted for at least six months. This case highlights that cytogenetics/FISH study alone may be insufficient to detect all PDGFRB rearrangement, which is critical for the patient's management. We suggest that molecular analysis capable of detecting fusion genes should be performed in all similar cases.
血小板衍生生长因子受体B（PDGFRB）重排是“伴有嗜酸性粒细胞增多和PDGFRB重排的髓系/淋系肿瘤”中典型的细胞遗传学异常，通常采用常规细胞遗传学方法即可明确。本文报告了1例特殊病例，其核型分析和荧光原位杂交（FISH）分析结果均为阴性，但通过二代测序（NGS）分析检测到了PDGFRB重排。该患者有大约1年的白细胞增多病史，包括中性粒细胞增多、嗜酸性粒细胞增多、嗜碱性粒细胞增多及粒细胞左移。骨髓活检显示骨髓细胞增多，伴有全髓增殖、嗜酸性粒细胞增多和肥大细胞增生。原始细胞未增多。辅助检查显示核型正常，且不存在BCR-ABL1融合基因。NGS鉴定出AFAP1L1-PDGFRB融合，通过聚合酶链反应扩增及直接Sanger测序得以证实。该患者接受伊马替尼治疗后外周血白细胞增多恢复正常，且持续至少6个月。该病例强调，仅依靠细胞遗传学/FISH研究可能不足以检测到所有的PDGFRB重排，而这对患者的治疗管理至关重要。我们建议，对于所有类似病例均应进行能够检测融合基因的分子分析。
