Myeloid neoplasms with eosinophilia and abnormalities of the PDGFRA gene can benefit from therapy with tyrosine kinase inhibitors, therefore revealing the PDGFRA rearrangement is essential to ensure the best choice of treatment. The most common PDGFRA partner is the FIP1L1 gene, generating the oncoprotein FIP1L1/PDGFRA (F/P). In the majority of cases the F/P fusion gene originates from intrachromosomal rearrangement at band 4q12, and occasionally from chromosomal translocations. In both cases, the interstitial chromosomal deletion of a region involving the CHIC2 gene has been reported, which is cryptic by conventional karyotyping but detectable by Fluorescence In Situ Hybridization (FISH) analyses. Herein, we report an acute myeloid leukemia (AML) case presenting with eosinophilia; the F/P fusion gene originated from a new, cryptic and complex intrachromosomal rearrangement of 4q12. Classical FISH assay revealed abnormal hybridization signals, but the presence of the F/P chimaeric gene was demonstrated by molecular analysis. We performed molecular characterization of the chromosomal rearrangement and targeted Next-Generation Sequencing (NGS) analysis with a myeloid gene panel, revealing the presence of pathogenic genomic variants affecting the TET2 and ETV6 genes. These mutations were present as subclones at the disease onset and their clone size increased at relapse.

嗜酸性粒细胞增多和PDGFRA基因异常的骨髓瘤可从酪氨酸激酶抑制剂的治疗中受益，因此揭示PDGFRA重排对于确保最佳治疗选择至关重要。PDGFRA最常见的伴侣是FIP1L1基因，产生癌蛋白FIP1L1 / PDGFRA（F / P）。在大多数情况下，F / P融合基因起源于4q12带的染色体内重排，偶尔也来自染色体易位。在这两种情况下，涉及CHIC2的区域的间质染色体缺失已经报道了该基因，其通过常规核型分析是隐秘的，但是可以通过荧光原位杂交（FISH）分析检测到。在此，我们报告了急性粒细胞白血病（AML）病例，表现为嗜酸性粒细胞增多。所述˚F / P融合基因源自的4q12一种新的，隐蔽的，复杂的染色体内重排。经典FISH分析显示异常杂交信号，但F / P存在通过分子分析证实了嵌合基因。我们进行了染色体重排的分子表征，并通过髓样基因组进行了靶向的下一代测序（NGS）分析，揭示了影响TET2和ETV6基因的致病基因组变异体的存在。这些突变在疾病发作时以亚克隆的形式出现，并且它们的克隆大小在复发时增加。