Leukemia ( IF 12.8 ) Pub Date : 2024-10-17 , DOI: 10.1038/s41375-024-02421-5 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
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%).
中文翻译:
CD36 细胞表面表达作为替代标志物鉴定儿科 BCP-ALL 中 ABL/JAK 类激酶融合
遗传改变是 B 细胞前体急性淋巴细胞白血病 (BCP-ALL) 风险分层的基础,其准确鉴定对于最佳治疗至关重要。大多数 ABL 类融合病例被归类为高风险,但对酪氨酸激酶抑制剂 (TKI) 表现出良好的反应。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。我们在这里研究了与这些分子改变相关的免疫表型特征的鉴定是否是一种有价值的筛选工具。CD36 表达被证明是 ABL 或 JAK 类激酶融合的特征。还发现在具有 Philadelphia (Ph) 样特征的子集中聚集的主要遗传亚群表现出特异性免疫表型特征。生成预测性多参数评分系统,分离激酶激活异常的遗传亚型 (PAX5/CRLF2alt、BCR::ABL1、ABL/JAK 类)。鉴定出的最稳健的标志物是具有 CD19/22/9/38/81/304 和 CD49f 的 TSLPR。由于 TKI 结合目前仅限于 ABL 类激酶融合,因此还研究了区分 ABL 和 JAK 类的免疫表型。因此,这里报道的流式细胞术方法可供大多数血液学部门使用,是一种新的有用工具,可以快速筛选 Ph 样激酶融合,具有良好的灵敏度 (95%) 和特异性 (96%)。