- •The chameleon like variability and rarity of TK driven MLN-eos may delay correct diagnosis and thus the use of targeted therapies.
- •Additional evaluation with fluorescence in-situ hybridization, array-based comparative genomic hybridization and RNA sequencing are recommended.
- •First reported cases of a TNIP1::PDGFRB and PCM1::FGFR1 fusion leading to myeloid/lymphoid neoplasms with eosinophilia in children.
Myeloid/lymphoid neoplasms with eosinophilia (MLN-eos) are rare haematological neoplasms primarily affecting adults. The heterogeneous clinical picture and the rarity of the disease, especially in children, may delay an early diagnosis. MLN-eos are characterized by constitutive tyrosine kinase (TK) activity due to gene fusions. It is thus of importance to obtain a prompt genetic diagnosis to start a specific therapy.
Here, we outline the clinical, genetic, and biochemical background of TK driven MLN-eos and report two extremely rare paediatric cases of MLN-eo, the used diagnostic methods, therapy and clinical outcomes.
Our results demonstrate that, standard cytogenetic and molecular methods may not be sufficient to diagnose MLN-eo due to cytogenetically cryptic aberrations. We therefore recommend performing additional evaluation with fluorescence in-situ hybridization and molecular genetic methods (array-based comparative genomic hybridization and RNA sequencing) which will lead to the correct diagnosis. Following this diagnostic route we detected a TNIP1::PDGFRB and a PCM1::FGFR1 fusion in our patients. Thus, genetic diagnosis must be precise and quick in order to initiate adequate therapies with tyrosine kinase inhibitors or HSCT.
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- Myeloid neoplasms with eosinophilia.Blood. 2017; 129: 704-714
- Tyrosine kinase fusion genes in chronic myeloproliferative diseases.Leukemia. 2002; 16: 1207-1212
- World Health Organization-defined eosinophilic disorders: 2022 update on diagnosis, risk stratification, and management.Am J Hematol. 2022; 97: 129-148
- Myeloid neoplasm with eosinophilia and rearrangement of platelet-derived growth factor receptor beta gene in children: Two case reports.World J Clin Cases. 2021; 9: 204-210
- Congenital and childhood myeloproliferative disorders with eosinophilia responsive to imatinib.Pediatr Blood Cancer. 2012; 59: 928-929
- Classical and Molecular Cytogenetics of Tumor Cells.(editor)in: Wegner R-D Diagnostic cytogenetics. Springer Berlin Heidelberg, Berlin, Heidelberg1999: 151-185
Schmid M. MG-JJ, Simons A. ISCN 2016: an international system for human cytogenomic nomenclature (2016) Basel, Freiburg: S. Karger GmbH 2016.
- Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Genet Med. 2015; 17: 405-424
- Delayed diagnosis leading to accelerated-phase chronic eosinophilic leukemia due to a cytogenetically cryptic, imatinib-responsive TNIP1-PDFGRB fusion gene.Leukemia. 2016; 30: 1402-1405
- The importance of cytogenetic and molecular analyses in eosinophilia-associated myeloproliferative neoplasms: an unusual case with normal karyotype and TNIP1- PDGFRB rearrangement and overview of PDGFRB partner genes.Leuk Lymphoma. 2017; 58: 489-493
- Patients with myeloid malignancies bearing PDGFRB fusion genes achieve durable long-term remissions with imatinib.Blood. 2014; 123: 3574-3577
- Maintenance therapy with imatinib appears necessary despite molecular remission in FIP1L1-PDGFRA fusion gene positive hypereosinophilic disorder.Leuk Res. 2008; 32: 169-171
- Targeted FGFR inhibition results in a durable remission in an FGFR1-driven myeloid neoplasm with eosinophilia.Blood Adv. 2020; 4: 3136-3140
- Clinical outcomes of myeloid/lymphoid neoplasms with fibroblast growth factor receptor-1 (FGFR1) rearrangement.Hematology. 2018; 23: 470-477
- FGF/FGFR signaling in health and disease.Signal Transduct Target Ther. 2020; 5: 181
Published online: January 06, 2023
Accepted: January 5, 2023
Received in revised form: November 11, 2022
Received: April 14, 2022
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