文章：

通过光学基因组映射检测髓系肿瘤中KMT2A部分串联重复：相关细胞遗传学、基因突变、治疗反应及患者预后

Detection ofKMT2APartial Tandem Duplication by Optical Genome Mapping in Myeloid Neoplasms: Associated Cytogenetics, Gene Mutations, Treatment Responses, and Patient Outcomes

原文发布日期：16 December 2024

DOI: 10.3390/cancers16244193

类型: Article

开放获取: 是

英文摘要：

KMT2Apartial tandem duplication (PTD) involves intragenicKMT2Aduplications and has been associated with poorer prognosis. In this study, we evaluatedKMT2APTD in 1277 patients with hematological malignancies using optical genome mapping (OGM).KMT2APTD was detected in 35 patients with acute myeloid leukemia (AML) (7%), 5 patients with myelodysplastic syndrome (MDS) (2.2%), and 5 patients with chronic myelomonocytic leukemia (CMML) (7.1%). The PTDs varied in size, region, and copy number. An Archer RNA fusion assay confirmedKMT2APTD in all 25 patients tested: 15 spanning exons 2 to 8 and 10 spanning exons 2 to 10. Most patients exhibited a normal (n= 21) or non-complex (n= 20) karyotype. The most common chromosomal abnormalities included loss of 20q or 7q and trisomy 11/gain of 11q. All patients had gene mutations, withFLT3ITD andDNMT3Aprevalent in AML andDNMT3AandRUNX1common in MDS and CMML. Among patients who received treatment and had at least one follow-up bone marrow evaluation, 82% of those with de novo AML achieved complete remission after initial induction chemotherapy, whereas 90% of patients with secondary or refractory/relapsed AML showed refractory or partial responses. All but one patient with MDS and CMML were refractory to therapy. We conclude that OGM is an effective tool for detectingKMT2APTD. Neoplasms withKMT2APTD frequently harbor gene mutations and display normal or non-complex karyotypes. Patients withKMT2APTD are generally refractory to conventional therapy, except for de novo AML.

摘要翻译： 

KMT2A部分串联重复（PTD）涉及KMT2A基因内重复，并与不良预后相关。本研究采用光学基因组图谱技术（OGM）对1277例血液系统恶性肿瘤患者进行了KMT2A PTD检测。在35例急性髓系白血病（AML）患者（7%）、5例骨髓增生异常综合征（MDS）患者（2.2%）和5例慢性粒单核细胞白血病（CMML）患者（7.1%）中检测到KMT2A PTD。这些PTD在大小、区域和拷贝数方面存在差异。Archer RNA融合检测在全部25例受试患者中均证实存在KMT2A PTD：其中15例跨越外显子2至8，10例跨越外显子2至10。多数患者表现为正常核型（n=21）或非复杂核型（n=20）。最常见的染色体异常包括20q或7q缺失以及11号染色体三体/11q获得。所有患者均存在基因突变，其中AML患者以FLT3 ITD和DNMT3A突变为主，而MDS和CMML患者中DNMT3A和RUNX1突变较为常见。在接受治疗且至少完成一次骨髓随访评估的患者中，82%的原发性AML患者在初始诱导化疗后达到完全缓解，而90%的继发性或难治/复发AML患者表现为难治性或部分缓解。除一例患者外，所有MDS和CMML患者均对治疗无反应。我们得出结论：OGM是检测KMT2A PTD的有效工具。携带KMT2A PTD的肿瘤常伴有基因突变，并呈现正常或非复杂核型。除原发性AML外，具有KMT2A PTD的患者通常对常规治疗耐药。

原文链接：

Detection ofKMT2APartial Tandem Duplication by Optical Genome Mapping in Myeloid Neoplasms: Associated Cytogenetics, Gene Mutations, Treatment Responses, and Patient Outcomes