Department of Pediatric Hematology-Oncology, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat-Gan, Israel,
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel,
Acta Haematol. 2019;141(2):119-127. doi: 10.1159/000495687. Epub 2019 Feb 6.
The WHO defined myeloid and lymphoid neoplasms (MLN) with eosinophilia associated with PDGFRB, PDGFRA, FGFR1 rearrangements as a new entity in 2016. PDGFRB-rearranged MLN sensitive to imatinib were described in adult patients. We report the first pediatric patient with PDGFRB-rearranged myeloproliferative disorder associated with T-lymphoblastic lymphoma bearing the t(5; 14)(q33;q32) translocation who was successfully treated with imatinib only. Methods/Aims: Analysis of bone marrow and peripheral blood cells by fluorescent in situ hybridization identified the PDGFRB partner as CCDC88C. Whole genome sequencing of the patient's DNA identified the exact junction site, confirmed by PCR amplification and Sanger sequencing. A real-time quantitative PCR assay was designed to quantify the fused CCDC88C-PDGFRB product.
A 2.5-year-old boy was diagnosed with myeloproliferative disorder and eosinophilia associated with lymphoblastic lymphoma both bearing the CCDC88C-PDGFRB fusion. Imatinib therapy resulted in rapid clinical, hematological, and cytogenetic response. Molecular response to treatment was monitored by a real-time PCR assay specific for the CCDC88C- PDGFRB fusion.
This is the first description of MLN with eosinophilia in the pediatric age group. Response to treatment with imatinib only was monitored by specific quantitative PCR assay with sustained remission lasting 5.5 years from diagnosis.
世界卫生组织（WHO）于 2016 年将伴有 PDGFRB、PDGFRA、FGFR1 重排的伴嗜酸性粒细胞增多的髓系和淋巴系肿瘤（MLN）定义为一种新实体。已在成人患者中描述了对伊马替尼敏感的 PDGFRB 重排 MLN。我们报告了首例伴有 T 淋巴母细胞淋巴瘤的 PDGFRB 重排骨髓增生性疾病伴 t（5; 14）（q33; q32）易位的儿科患者，仅用伊马替尼治疗即获得成功。方法/目的：通过荧光原位杂交分析骨髓和外周血细胞，鉴定出 PDGFRB 伙伴为 CCDC88C。对患者 DNA 进行全基因组测序，确定了确切的连接位点，通过 PCR 扩增和 Sanger 测序进行了验证。设计了实时定量 PCR 检测方法来定量融合的 CCDC88C-PDGFRB 产物。结果：一名 2.5 岁男孩被诊断为伴有淋巴母细胞淋巴瘤的骨髓增生性疾病和伴嗜酸性粒细胞增多，均伴有 CCDC88C-PDGFRB 融合。伊马替尼治疗导致快速的临床、血液学和细胞遗传学反应。通过针对 CCDC88C-PDGFRB 融合的实时 PCR 检测方法监测治疗的分子反应。结论：这是首例儿科年龄组伴嗜酸性粒细胞增多的 MLN 描述。仅用伊马替尼治疗的反应通过特异性定量 PCR 检测进行监测，从诊断起持续缓解 5.5 年。
