{"title":"将CD36细胞表面表达作为替代标记物,以确定小儿BCP-ALL中的ABL/JAK类激酶融合情况","authors":"Marion Strullu, Aurélie Caye-Eude, Elie Robert, Jean-Marie Renard, Amandine Chaye, Julie Galimand, Odile Fenneteau, Chloé Arfeuille, Wendy Cuccuini, Alexandre Theron, Sandrine Thouvenin, Catherine Paillard, Arnaud Petit, Pierre-Simon Rohrlich, Hélène Cavé, André Baruchel, Elodie Lainey","doi":"10.1038/s41375-024-02421-5","DOIUrl":null,"url":null,"abstract":"<p>Genetic alterations are the cornerstone of risk stratification in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), and their accurate identification is critical for optimal treatment. Most cases with <i>ABL</i>-class fusion are classified as high-risk yet display good responses to tyrosine kinase inhibitors (TKIs). Current clinical protocols recommend adding a TKI to chemotherapy as soon as possible, making it mandatory to rapidly identify these alterations. 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The flow cytometry method reported here, accessible to most hematology departments, is thus a new useful tool to quickly screen for Ph-like kinase fusion with a good sensitivity (95%) and specificity (96%).</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"78 1","pages":""},"PeriodicalIF":12.8000,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"CD36 cell surface expression as a surrogate marker to identify ABL/JAK-class kinase fusions in pediatric BCP-ALL\",\"authors\":\"Marion Strullu, Aurélie Caye-Eude, Elie Robert, Jean-Marie Renard, Amandine Chaye, Julie Galimand, Odile Fenneteau, Chloé Arfeuille, Wendy Cuccuini, Alexandre Theron, Sandrine Thouvenin, Catherine Paillard, Arnaud Petit, Pierre-Simon Rohrlich, Hélène Cavé, André Baruchel, Elodie Lainey\",\"doi\":\"10.1038/s41375-024-02421-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Genetic alterations are the cornerstone of risk stratification in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), and their accurate identification is critical for optimal treatment. 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引用次数: 0
摘要
基因改变是 B 细胞前体急性淋巴细胞白血病(BCP-ALL)风险分层的基石,准确识别基因改变对优化治疗至关重要。大多数 ABL 级融合病例被列为高危病例,但对酪氨酸激酶抑制剂(TKIs)的反应良好。目前的临床方案建议尽快在化疗中加入 TKI,因此必须快速识别这些改变。我们在此研究了与这些分子改变相关的免疫表型特征的识别是否可以成为一种有价值的筛选工具。结果显示,CD36的表达是ABL-或JAK-类激酶融合的一个特征。研究还发现,具有费城(Ph)样特征的主要基因亚群也显示出特定的免疫表型特征。该研究生成了一个预测性多参数评分系统,可分离出具有异常激酶激活(PAX5/CRLF2alt、BCR::ABL1、ABL/JAK-class)的基因亚型。确定的最可靠标记是 TSLPR 与 CD19/22/9/38/81/304 和 CD49f。由于 TKI 连接目前仅限于 ABL 类激酶融合,因此还研究了区分 ABL 和 JAK 类的免疫表型。本文报告的流式细胞术方法大多数血液科都能使用,因此是快速筛查类Ph激酶融合的一种新的有用工具,具有良好的灵敏度(95%)和特异性(96%)。
CD36 cell surface expression as a surrogate marker to identify ABL/JAK-class kinase fusions in pediatric BCP-ALL
Genetic alterations are the cornerstone of risk stratification in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), and their accurate identification is critical for optimal treatment. Most cases with ABL-class fusion are classified as high-risk yet display good responses to tyrosine kinase inhibitors (TKIs). Current clinical protocols recommend adding a TKI to chemotherapy as soon as possible, making it mandatory to rapidly identify these alterations. We investigated here whether the identification of immunophenotypic features associated with these molecular alterations could be a valuable screening tool. CD36 expression was shown to be a characteristic feature of ABL- or JAK-class kinase fusions. The main genetic subgroups clustering in the subset with Philadelphia (Ph)-like features were also found to display specific immunophenotypic characteristics. A predictive multiparameter scoring system was generated, segregating genetic subtypes with aberrant kinase activation (PAX5/CRLF2alt, BCR::ABL1, ABL/JAK-class). The most robust markers identified were the TSLPR with CD19/22/9/38/81/304 and CD49f. As TKI adjunction is currently limited to the ABL-class kinase fusions, immunophenotypes distinguishing ABL from JAK-class were also investigated. The flow cytometry method reported here, accessible to most hematology departments, is thus a new useful tool to quickly screen for Ph-like kinase fusion with a good sensitivity (95%) and specificity (96%).
期刊介绍:
Title: Leukemia
Journal Overview:
Publishes high-quality, peer-reviewed research
Covers all aspects of research and treatment of leukemia and allied diseases
Includes studies of normal hemopoiesis due to comparative relevance
Topics of Interest:
Oncogenes
Growth factors
Stem cells
Leukemia genomics
Cell cycle
Signal transduction
Molecular targets for therapy
And more
Content Types:
Original research articles
Reviews
Letters
Correspondence
Comments elaborating on significant advances and covering topical issues