How I (Diagnose and) Treat Myeloid / Lymphoid Neoplasms with Tyrosine Kinase Gene Fusions.
Andreas ReiterGeorgia MetzgerothNicholas C P CrossPublished in: Blood (2024)
The fifth edition of the WHO classification and the International Consensus Classification (ICC) both include a category "myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase (TK) gene fusions" (WHO, MLN-TK; ICC, M/LN-eo-TK). This rare group comprises phenotypically and prognostically heterogeneous disorders that 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, which include chronic phase and primary/secondary blast phase (BP) of myeloid, or 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. Since primary/secondary BP-BM/EMD occur more frequently in MLN-FGFR1/JAK2/FLT3/ETV6::ABL1, a sequential combination of selective TKIs with or without prior intensive chemotherapy, rarely local local radiationradiotherapy and/or subsequent allogeneic hematopoietic cell transplantation should be considered.
Keyphrases
- tyrosine kinase
- bone marrow
- genome wide
- epidermal growth factor receptor
- genome wide identification
- copy number
- acute myeloid leukemia
- dendritic cells
- machine learning
- dna methylation
- single cell
- deep learning
- mesenchymal stem cells
- bioinformatics analysis
- stem cell transplantation
- acute lymphoblastic leukemia
- clinical practice
- randomized controlled trial
- squamous cell carcinoma
- clinical trial
- low dose
- high dose
- immune response
- single molecule
- chronic myeloid leukemia
- sensitive detection