A RUNX1: RUNX1T1 AML with a simultaneous false positive KMT2A rearrangement: FISH interpretation pitfalls.

IF 2 4区医学 Q3 HEMATOLOGY

Hematology Pub Date : 2024-12-01 Epub Date: 2024-11-13 DOI:10.1080/16078454.2024.2420306

Chi Zhang, Xingping Lang, Lingfeng Liu, Nan Chen, Huafei Chen, Xiaojun Chen, Yongyan Chen, Liqin Jin, Chengyin Liu, Huan Wang, Ailin Fu, Sheng Xiao

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引用次数: 0

Abstract

Introduction: KMT2A rearrangement (KMT2Ar) is a common genomic alteration in acute leukemia that can be effectively targeted by menin inhibitors. While FISH is the standard laboratory test for KMT2Ar, false positives can occur.

Case report: We present a case of AML in which both RUNX1::RUNX1T1 and KMT2Ar were identified by karyotype analysis and FISH. Although a targeted RNA next generation sequencing (NGS) assay confirmed the presence of the RUNX1::RUNX1T1 fusion, it did not detect a KMT2A fusion transcript. To investigate the discrepancy between the positive KMT2A FISH result and the negative fusion transcript, we performed whole-genome mate-pair DNA NGS to examine the KMT2A locus on chromosome 11q23. This analysis revealed a breakpoint located 5.8 kb downstream of KMT2A, which did not disrupt the gene itself. Given that KMT2A FISH probes cover approximately 1 Mb around KMT2A, this subtle shift led to a split-apart signal pattern mimicking a genuine KMT2A rearrangement, resulting in a false positive FISH interpretation.

Conclusion: This case highlights a false positive KMT2Ar in primary AML, indicating the need for additional molecular testing for confirmation.

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RUNX1：RUNX1T1急性髓细胞性白血病同时伴有KMT2A重排假阳性：FISH解读陷阱。

简介KMT2A重排（KMT2Ar）是急性白血病中常见的基因组改变，menin抑制剂可以有效地针对这种改变。虽然 FISH 是 KMT2Ar 的标准实验室检测方法，但也可能出现假阳性：我们报告了一例急性髓细胞白血病病例，该病例通过核型分析和 FISH 发现了 RUNX1::RUNX1T1 和 KMT2Ar。虽然靶向 RNA 下一代测序（NGS）检测证实了 RUNX1::RUNX1T1 融合的存在，但并未检测到 KMT2A 融合转录本。为了研究 KMT2A FISH 阳性结果与阴性融合转录本之间的差异，我们进行了全基因组配对 DNA NGS，以检测染色体 11q23 上的 KMT2A 基因座。这项分析发现了位于 KMT2A 下游 5.8 kb 的断点，但该断点并未破坏基因本身。鉴于 KMT2A FISH 探针覆盖了 KMT2A 周围约 1 Mb 的范围，这种微妙的移动导致了模仿真正的 KMT2A 重排的分裂信号模式，从而导致了 FISH 解释的假阳性：本病例突出显示了原发性急性髓细胞性白血病的 KMT2Ar 假阳性，表明需要进行额外的分子检测来确认。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hematology 医学-血液学

CiteScore

2.60

自引率

5.30%

发文量

140

审稿时长

3 months

期刊介绍： Hematology is an international journal publishing original and review articles in the field of general hematology, including oncology, pathology, biology, clinical research and epidemiology. Of the fixed sections, annotations are accepted on any general or scientific field: technical annotations covering current laboratory practice in general hematology, blood transfusion and clinical trials, and current clinical practice reviews the consensus driven areas of care and management.