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TLE3 Is a Novel Fusion Partner of JAK2 in Myeloid/Lymphoid Neoplasm With Eosinophilia Responding to JAK2 Inhibition
Vladimir Lazarevic1, Henrik Lilljebjörn2, Linda Olsson-Arvidsson2,3
1Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden.
Abstract:
Chromosomal rearrangements involving Janus kinase 2 (JAK2) are rare but recurrent findings in lymphoid or myeloid neoplasia. Detection of JAK2 fusion genes is important as patients with aberrantly activated JAK2 may benefit from treatment with tyrosine kinase inhibitors such as ruxolitinib. Here, we report a novel fusion gene between the transcriptional co-repressor-encoding gene transducin-like enhancer of split 3 (TLE3) and JAK2 in a patient initially diagnosed with chronic eosinophilic leukemia with additional mutations in PTPN11 and NRAS. The patient was successfully treated with the JAK2 inhibitor ruxolitinib for 8 months before additional somatic mutations were acquired and the disease progressed into an acute lymphoblastic T-cell leukemia/lymphoma. The present case shows similarities to previously reported cases with PCM1::JAK2 and BCR::JAK2 with regard to disease phenotype and response to ruxolitinib, and importantly, provides an example that also patients harboring other JAK2 fusion genes may benefit from treatment with JAK2 inhibitors.
Insights
This study reports a novel TLE3::JAK2 fusion gene in a patient with chronic eosinophilic leukemia. The patient responded well to JAK2 inhibitor ruxolitinib, highlighting its potential for treating rare JAK2 fusion gene-driven cancers.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Chromosomal rearrangements involving Janus kinase 2 (JAK2) are implicated in lymphoid and myeloid neoplasms.
- Identifying JAK2 fusion genes is crucial for targeted therapy with tyrosine kinase inhibitors like ruxolitinib.
- Aberrant JAK2 activation can drive neoplastic processes, necessitating precise diagnostic approaches.
Purpose of the Study:
- To report a novel TLE3::JAK2 fusion gene in a patient with chronic eosinophilic leukemia.
- To investigate the clinical course and treatment response in a patient with this rare genetic alteration.
- To underscore the therapeutic potential of JAK2 inhibitors in diverse JAK2 fusion gene contexts.
Main Methods:
- Case report of a patient with chronic eosinophilic leukemia.
- Genetic analysis to identify novel fusion genes.
- Clinical monitoring of treatment response to ruxolitinib.
Main Results:
- A novel TLE3::JAK2 fusion gene was identified.
- The patient achieved an 8-month remission with ruxolitinib treatment.
- Disease progression occurred with acquisition of new mutations, leading to T-cell acute lymphoblastic leukemia/lymphoma.
Conclusions:
- The TLE3::JAK2 fusion represents a rare but actionable genetic event in myeloid neoplasia.
- Targeted therapy with JAK2 inhibitors can be effective in patients with various JAK2 fusion genes.
- This case expands the spectrum of JAK2 fusion genes responsive to ruxolitinib, offering therapeutic insights.
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