Reiter Andreas, Metzgeroth Georgia, Cross Nicholas C P
Hematology and Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany.
Wessex Genomics Laboratory Service, Salisbury, United Kingdom.
Blood. 2025 Apr 17;145(16):1758-1768. doi: 10.1182/blood.2023022417.
The fifth edition of the World Health Organization (WHO) classification and the International Consensus Classification (ICC) both include a category "myeloid/lymphoid neoplasms (MLN) with eosinophilia (eo) and tyrosine kinase (TK) gene fusions" (WHO, MLN-TK; ICC, M/LN-eo-TK). This rare group comprises phenotypically and prognostically heterogeneous disorders, which present a significant diagnostic challenge. The rapid and reliable identification of patients with MLN-TK may be delayed due to genetic complexity and significant phenotypic differences, including the chronic phase and primary/secondary blast phase (BP) of myeloid, lymphoid, or mixed phenotype in the bone marrow (BP-BM) and/or at extramedullary sites (extramedullary disease [EMD]). As a result, the entire armamentarium of conventional molecular genetic and cytogenetic techniques complemented by modern sequencing technologies, such as RNA sequencing or whole-genome sequencing, are often required to identify an underlying TK fusion. TK inhibitors (TKIs) with variable efficacy are available for all fusion genes, but a long-term favorable clinical course under TKI monotherapy is currently only observed in MLN-PDGFRA/PDGFRB fusion genes on imatinib. Because primary/secondary BP-BM/EMD occurs more frequently in MLN-FGFR1/JAK2/FLT3/ETV6::ABL1, a sequential combination of selective TKIs with or without prior intensive chemotherapy, rarely local radiotherapy, and/or subsequent allogeneic hematopoietic cell transplantation should be considered.
世界卫生组织（WHO）分类的第五版和国际共识分类（ICC）均包含一个类别，即“伴有嗜酸性粒细胞增多（eo）和酪氨酸激酶（TK）基因融合的髓系/淋系肿瘤（MLN）”（WHO分类为MLN-TK；ICC分类为M/LN-eo-TK）。这一罕见的肿瘤组包括表型和预后异质性疾病，给诊断带来了重大挑战。由于基因复杂性和显著的表型差异，包括骨髓（BP-BM）和/或髓外部位（髓外疾病[EMD]）的髓系、淋系或混合表型的慢性期以及原发性/继发性急变期（BP），MLN-TK患者的快速、可靠识别可能会延迟。因此，通常需要结合传统分子遗传学和细胞遗传学技术，并辅以现代测序技术，如RNA测序或全基因组测序，来识别潜在的TK融合。针对所有融合基因均有疗效各异的TK抑制剂（TKIs），但目前仅在接受伊马替尼治疗的MLN-PDGFRA/PDGFRB融合基因患者中观察到TKI单药治疗下的长期良好临床病程。由于原发性/继发性BP-BM/EMD在MLN-FGFR1/JAK2/FLT3/ETV6::ABL1中更常见，应考虑选择性TKIs序贯联合治疗，可联合或不联合前期强化化疗，很少联合局部放疗，和/或后续的异基因造血细胞移植。
