Sahin Yavuz, Pei Jianming, Baldwin Don A, Mansoor Nashwa, Koslosky Lori, Abdelmessieh Peter, Wang Y Lynn, Nejati Reza, Testa Joseph R
Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Department of Bone Marrow Transplant and Cellular Therapies, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Leuk Res Rep. 2024 May 31;21:100465. doi: 10.1016/j.lrr.2024.100465. eCollection 2024.
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 mutation transforming to AML characterized by a previously unreported 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.
急性髓系白血病（AML）是一种异质性血液系统恶性肿瘤，与基因突变、表观遗传异常以及染色体重排相关基因融合的多种组合有关。尽管其发病机制存在显著的异质性程度，但许多基因融合和点突变在AML中反复出现，并在过去几十年中被用于风险分层。长期以来，基因融合在理解肿瘤发生及其在临床诊断和靶向治疗中的已证实作用方面得到了认可。DNA测序技术和计算生物学的进展对已知融合基因的检测以及新融合基因的发现做出了重大贡献。AML中几种反复出现的基因融合与预后、治疗反应和疾病进展有关。在本报告中，我们呈现了一例有原发性血小板增多症长期病史且特征性突变转化为AML的病例，其特征为一个先前未报道的融合基因。我们提出了这种融合可能导致AML发病机制的机制及其作为酪氨酸激酶抑制剂分子靶点的潜力。
