Vandenberghe P, Wlodarska I, Michaux L, Zachée P, Boogaerts M, Vanstraelen D, Herregods M-C, Van Hoof A, Selleslag D, Roufosse F, Maerevoet M, Verhoef G, Cools J, Gilliland D G, Hagemeijer A, Marynen P
The Center for Human Genetics, University Hospital Leuven, Leuven, Belgium.
Leukemia. 2004 Apr;18(4):734-42. doi: 10.1038/sj.leu.2403313.
Detection of the FIP1L1-PDGFRA fusion gene or the corresponding cryptic 4q12 deletion supports the diagnosis of chronic eosinophilic leukemia (CEL) in patients with chronic hypereosinophilia. We retrospectively characterized 17 patients fulfilling WHO criteria for idiopathic hypereosinophilic syndrome (IHES) or CEL, using nested RT-PCR and interphase fluorescence in situ hybridization (FISH). Eight had FIP1L1-PDGFRA (+) CEL, three had FIP1L1-PDGFRA (-) CEL and six had IHES. FIP1L1-PDGFRA (+) CEL responded poorly to steroids, hydroxyurea or interferon-alpha, and had a high probability of eosinophilic endomyocarditis (n=4) and disease-related death (n=4). In FIP1L1-PDGFRA (+) CEL, palpable splenomegaly was present in 5/8 cases, serum vitamin B(12) was always markedly increased, and marrow biopsies revealed a distinctively myeloproliferative aspect. Imatinib induced rapid complete hematological responses in 4/4 treated FIP1L1-PDGFRA (+) cases, including one female, and complete molecular remission in 2/3 evaluable cases. In the female patient, 1 log reduction of FIP1L1-PDGFRA copy number was reached as by real-time quantitative PCR (RQ-PCR). Thus, correlating IHES/CEL genotype with phenotype, FIP1L1-PDGFRA (+) CEL emerges as a homogeneous clinicobiological entity, where imatinib can induce molecular remission. While RT-PCR and interphase FISH are equally valid diagnostic tools, the role of marrow biopsy in diagnosis and of RQ-PCR in disease and therapy monitoring needs further evaluation.
检测FIP1L1-PDGFRA融合基因或相应的隐匿性4q12缺失有助于诊断慢性嗜酸性粒细胞白血病（CEL）合并慢性嗜酸性粒细胞增多症患者。我们采用巢式逆转录聚合酶链反应（RT-PCR）和间期荧光原位杂交（FISH）对17例符合世界卫生组织（WHO）特发性嗜酸性粒细胞增多综合征（IHES）或CEL标准的患者进行了回顾性分析。8例为FIP1L1-PDGFRA（+）CEL，3例为FIP1L1-PDGFRA（-）CEL，6例为IHES。FIP1L1-PDGFRA（+）CEL对类固醇、羟基脲或α干扰素反应不佳，发生嗜酸性粒细胞性心内膜炎（n = 4）和疾病相关死亡（n = 4）的可能性较高。在FIP1L1-PDGFRA（+）CEL中，5/8的病例可触及脾肿大，血清维生素B12总是显著升高，骨髓活检显示明显的骨髓增殖特征。伊马替尼在4/4例接受治疗的FIP1L1-PDGFRA（+）病例中诱导了快速完全血液学缓解，其中包括1名女性，在2/3例可评估病例中诱导了完全分子缓解。在该女性患者中，通过实时定量PCR（RQ-PCR）实现了FIP1L1-PDGFRA拷贝数降低1个对数。因此，将IHES/CEL基因型与表型相关联，FIP1L1-PDGFRA（+）CEL成为一个同质的临床生物学实体，伊马替尼可在其中诱导分子缓解。虽然RT-PCR和间期FISH是同样有效的诊断工具，但骨髓活检在诊断中的作用以及RQ-PCR在疾病和治疗监测中的作用需要进一步评估。
