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Abstract：
Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy associated with various combinations of gene mutations, epigenetic abnormalities, and chromosome rearrangement-related gene fusions. Despite the significant degree of heterogeneity in its pathogenesis, many gene fusions and point mutations are recurrent in AML and have been employed in risk stratification over the last several decades. Gene fusions have long been recognized for understanding tumorigenesis and their proven roles in clinical diagnosis and targeted therapies. Advances in DNA sequencing technologies and computational biology have contributed significantly to the detection of known fusion genes as well as for the discovery of novel ones. Several recurring gene fusions in AML have been linked to prognosis, treatment response, and disease progression. In this report, we present a case with a long history of essential thrombocythemia and hallmark CALR mutation transforming to AML characterized by a previously unreported AKAP9::PDGFRA fusion gene. We propose mechanisms by which this fusion may contribute to the pathogenesis of AML and its potential as a molecular target for tyrosine kinase inhibitors.
摘要：
急性髓系白血病（AML）是一种与各种基因突变组合相关的异质性血液系统恶性肿瘤，表观遗传异常,和染色体重排相关基因融合。尽管其发病机制具有显著的异质性,许多基因融合和点突变在AML中反复出现,并且在过去几十年中被用于危险分层.长期以来，人们一直认识到基因融合可以理解肿瘤发生及其在临床诊断和靶向治疗中的作用。DNA测序技术和计算生物学的进步为已知融合基因的检测以及新融合基因的发现做出了重要贡献。AML中几种反复出现的基因融合与预后有关，治疗反应,和疾病进展。在这份报告中,我们介绍了1例原发性血小板增多症的长期病史,其特征在于以前未报道的AKAP9::PDGFRA融合基因的CALR突变转化为AML.我们提出了这种融合可能有助于AML发病的机制及其作为酪氨酸激酶抑制剂分子靶标的潜力。
