新的PLEC-EML4-ALK双融合在转移性炎症性肌纤维母细胞肿瘤中的克唑替尼耐药性：1例报告

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports Pub Date : 2025-01-07 DOI:10.1016/j.jtocrr.2025.100791

Alessandra Maleddu MD , Trista K. Hinz MS , Margaret A. Black MD , Dara L. Aisner MD, PhD , Carrie B. Marshall MD , Anthony D. Elias MD , Breelyn A. Wilky MD , Lynn E. Heasley PhD , Kurtis D. Davies PhD

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引用次数: 0

摘要

ALK融合是炎性肌成纤维细胞肿瘤中常见的致癌驱动因素。克唑替尼治疗对融合阳性患者有效；然而，获得性耐药性仍然是一个挑战。在这里，我们报告了一例eml4 - alk阳性转移性炎性肌成纤维细胞肿瘤，最初对克唑替尼有反应，但后来产生了耐药性。进展的病变显示获得了“双融合”事件，其中EML4-ALK被额外融合到PLEC中，以创建PLEC-EML4-ALK转录物。双重融合与ALK表达的增加有关，模拟了ALK融合扩增，这是肺癌中对克唑替尼耐药的已知机制。在过渡到更有效的ALK抑制剂alectinib时，患者表现出戏剧性的反应。因此，双融合的形成代表了对克唑替尼耐药的一种新的和可靶向的机制。

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Novel PLEC-EML4-ALK Double Fusion Underlying Crizotinib Resistance in a Metastatic Inflammatory Myofibroblastic Tumor: A Case Report

ALK fusions are frequent oncogenic drivers in inflammatory myofibroblastic tumors. Treatment with crizotinib is effective in fusion-positive patients; however, acquired resistance remains a challenge. Here, we present a case of EML4-ALK-positive metastatic inflammatory myofibroblastic tumor that initially responded to crizotinib but developed resistance. The progressing lesion revealed the acquisition of a “double fusion” event in which EML4-ALK was additionally fused to PLEC to create a PLEC-EML4-ALK transcript. The double fusion was associated with an increase in ALK expression, mimicking the ALK fusion amplification that is a known mechanism of resistance to crizotinib in lung cancer. On transition to the more potent ALK inhibitor alectinib, the patient exhibited a dramatic response. Thus, the formation of a double fusion represents a novel and targetable mechanism of resistance to crizotinib.

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