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添加 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鉴定是否可以成为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。还发现聚集在具有费城（Ph）样特征的子集中的主要遗传亚群表现出特定的免疫表型特征。生成了预测性多参数评分系统，分离具有异常激酶激活的遗传亚型（PAX5/CRLF2alt、BCR::ABL1、ABL/JAK 类）。确定的最强大的标记是带有 CD19/22/9/38/81/304 和 CD49f 的 TSLPR。由于 TKI 辅助目前仅限于 ABL 类激酶融合，因此还研究了区分 ABL 和 JAK 类的免疫表型。本文报道的流式细胞术方法可供大多数血液科使用，因此是一种快速筛选 Ph 样激酶融合的新的有用工具，具有良好的灵敏度 (95%) 和特异性 (96%)。© 2024。作者），经 Springer Nature Limited 独家许可。

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%).© 2024. The Author(s), under exclusive licence to Springer Nature Limited.