How I diagnose and treat myeloid/lymphoid neoplasms with tyrosine kinase gene fusions

• Verfasst von: Reiter, Andreas [VerfasserIn]
• Verfasst von: Metzgeroth, Georgia [VerfasserIn]
• Verfasst von: Cross, Nicholas C. P. [VerfasserIn]
• Titel: How I diagnose and treat myeloid/lymphoid neoplasms with tyrosine kinase gene fusions
• Titelzusatz: how I treat series : myeloproliferative neoplasms
• Verf.angabe: Andreas Reiter, Georgia Metzgeroth, and Nicholas C.P. Cross
• E-Jahr: 2025
• Jahr: 17 April 2025
• Umfang: 11 S.
• Illustrationen: Diagramme
• Fussnoten: Online verfügbar: 26. Jul 2024, Artikelversion: 17. April 2025 ; Gesehen am 24.06.2025
• Titel Quelle: Enthalten in: Blood
• Ort Quelle: Washington, DC : American Society of Hematology, 1946
• Jahr Quelle: 2025
• Band/Heft Quelle: 145(2025), 16, Seite 1758-1768
• ISSN Quelle: 1528-0020
• DOI: doi:10.1182/blood.2023022417
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1928926002

Abstract

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.