Kluk Michael J, Abo Ryan P, Brown Ronald D, Kuo Frank C, Dal Cin Paola, Pozdnyakova Olga, Morgan Elizabeth A, Lindeman Neal I, DeAngelo Daniel J, Aster Jon C
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA;
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Cold Spring Harb Mol Case Stud. 2015 Oct;1(1):a000307. doi: 10.1101/mcs.a000307.
We describe the case of a patient presenting with several weeks of symptoms related to pancytopenia associated with a maturation arrest at the late promyelocyte/early myelocyte stage of granulocyte differentiation. A diagnosis of acute promyelocytic leukemia was considered, but the morphologic features were atypical for this entity and conventional tests for the presence of a PML-RARA fusion gene were negative. Additional analysis using a custom next-generation sequencing assay revealed a rearrangement producing a STAT5B-RARA fusion gene, which was confirmed by reverse transcription polymerase chain reaction (RT-PCR) and supplementary cytogenetic studies, allowing the diagnosis of a morphologically atypical form of acute promyelocytic leukemia to be made. Analysis of the sequencing data permitted characterization of both chromosomal breakpoints and revealed two additional alterations, a small deletion in RARA exon 9 and a RARA R276W substitution, that have been linked to resistance to all-trans retinoic acid. This case highlights how next-generation sequencing can augment currently standard testing to establish diagnoses in difficult cases, and in doing so help guide selection of therapy.
我们描述了一例患者，其出现了数周与全血细胞减少相关的症状，该全血细胞减少与粒细胞分化的早幼粒细胞晚期/早幼粒细胞早期成熟停滞有关。考虑诊断为急性早幼粒细胞白血病，但该实体的形态学特征不典型，且检测PML-RARA融合基因存在的常规检查结果为阴性。使用定制的下一代测序分析进行的进一步分析发现了一种重排，产生了STAT5B-RARA融合基因，这通过逆转录聚合酶链反应（RT-PCR）和补充细胞遗传学研究得到证实，从而得以诊断出形态学不典型的急性早幼粒细胞白血病。对测序数据的分析使得能够对两个染色体断点进行特征描述，并揭示了另外两个改变，即RARA外显子9的小缺失和RARA R276W替换，这些改变与对全反式维甲酸的耐药性有关。该病例凸显了下一代测序如何能够加强当前的标准检测，以在疑难病例中确立诊断，并以此帮助指导治疗选择。
