髓系肉瘤显示出激活MAPK/ERK通路的高频率突变,并与克隆造血相关

IF 3.7 2区 医学 Q1 PATHOLOGY
Dominik Nann, Tim-Colin Schade, Mathis Overkamp, Lejla Mahmutovic, Eyyub Bag, Stephan Forchhammer, Julia Slotta-Huspenina, Ludmila Boudova, Karl Sotlar, Leticia Quintanilla-Martinez, Irina Bonzheim, Falko Fend
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引用次数: 0

摘要

髓系肉瘤(MS)是髓系细胞在髓外形成的团块表现,可能与潜在的急性髓系白血病(AML)、另一种髓系肿瘤(MN)有关,也可能是新发病例。关于多发性硬化症遗传谱的数据很少。本研究采用靶向下一代测序(NGS)、基于rna的融合检测和基因表达谱(GEP)分析了34例41例MS患者,其中包括7例新发病例和24例既往或同步MN患者。10例患者在骨髓干细胞移植后发生多发性硬化症。此外,对20例患者的21例移植前骨髓活检(BMB)和6例患者的6例移植后骨髓活检(BMB)进行了研究。最常见的突变基因是TET2(41%),其次是NPM1(38%)和NRAS(35%)。总的来说,74%的病例表现出影响MAPK/ERK通路的突变。在7例MS患者中检测到aml型融合,他们比没有融合的患者年轻(中位年龄49岁对67岁)。13例MN和可用移植前BMB患者中有9例显示局限于MS的额外突变,包括3/5的AML患者中额外的NRAS突变。移植前BMB无MN证据的7例患者中有5例显示克隆造血(CH),大多数共享TET2突变。BM和MS的GEP比较显示MS中MAPK/ERK通路以及与微环境相互作用相关的基因组上调。综上所述,MS的特点是MAPK/ERK通路突变和激活发生率高,克隆进化频繁,并且在没有复发性aml型融合的老年患者中与CH相关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Myeloid sarcoma shows a high frequency of mutations activating the MAPK/ERK pathway and association with clonal hematopoiesis

Myeloid sarcoma shows a high frequency of mutations activating the MAPK/ERK pathway and association with clonal hematopoiesis

Myeloid sarcoma shows a high frequency of mutations activating the MAPK/ERK pathway and association with clonal hematopoiesis

Myeloid sarcoma shows a high frequency of mutations activating the MAPK/ERK pathway and association with clonal hematopoiesis

Myeloid sarcoma (MS) is a mass-forming extramedullary manifestation of myeloid blasts, either in relation to an underlying acute myeloid leukemia (AML), another myeloid neoplasm (MN) or as a de novo occurrence. Data on the genetic profile of MS are sparse. In this study, 41 MS of 34 patients, including 7 de novo cases and 24 patients with antecedent or synchronous MN, were analyzed with targeted next-generation sequencing (NGS), RNA-based fusion detection, and gene expression profiling (GEP). In 10 patients, a MS developed after stem cell transplantation for MN. Additionally, 21 available pre-transplant bone marrow biopsies (BMB) from 20 patients and 6 post-transplant BMB from 6 patients were investigated. The most frequently mutated gene was TET2 (41%), followed by NPM1 (38%) and NRAS (35%). Overall, 74% of the cases exhibited mutations affecting the MAPK/ERK pathway. AML-type fusions were detected in seven MS patients, who were younger than those without fusions (median 49 versus 67 years). Nine of 13 patients with a MN and available pre-transplant BMB showed additional mutations restricted to the MS, including an additional NRAS mutation in 3/5 cases with AML. Five of seven of patients with pre-transplant BMB without evidence of a MN revealed clonal hematopoiesis (CH), mostly shared TET2 mutations. Comparative GEP between BM and MS revealed upregulation of the MAPK/ERK pathway in MS and of gene sets relevant for interaction with the microenvironment. In conclusion, MS is characterized by a high incidence of MAPK/ERK pathway mutations and activation, frequent clonal evolution, and association with CH in elderly patients without recurrent AML-type fusions.

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来源期刊
Journal of Pathology Clinical Research
Journal of Pathology Clinical Research Medicine-Pathology and Forensic Medicine
CiteScore
7.40
自引率
2.40%
发文量
47
审稿时长
20 weeks
期刊介绍: The Journal of Pathology: Clinical Research and The Journal of Pathology serve as translational bridges between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The focus of The Journal of Pathology: Clinical Research is the publication of studies that illuminate the clinical relevance of research in the broad area of the study of disease. Appropriately powered and validated studies with novel diagnostic, prognostic and predictive significance, and biomarker discover and validation, will be welcomed. Studies with a predominantly mechanistic basis will be more appropriate for the companion Journal of Pathology.
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