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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
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Myeloid/lymphoid neoplasms with FLT3 rearrangement
Guilin Tang1, Wayne Tam2, Nicholas J Short3
1Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. gtang@mdanderson.org.
Summary
Myeloid/lymphoid neoplasms with FLT3 rearrangement often present with eosinophilia and multilineage involvement. These cases share features with other M/LN-eo, suggesting potential therapeutic benefits from kinase inhibitors.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Myeloid/lymphoid neoplasms (M/LN) with 13q12/FLT3 rearrangement are potential candidates for the M/LN with eosinophilia (M/LN-eo) WHO classification group.
- Recent studies suggest a link between specific gene rearrangements and M/LN-eo.
Purpose of the Study:
- To characterize the clinical and molecular features of M/LN with FLT3 rearrangement.
- To compare these neoplasms with known M/LN-eo entities.
Main Methods:
- Case series of 12 patients with confirmed FLT3 rearrangement.
- Review of 16 previously published cases.
- Next-generation sequencing for mutation analysis.
- Analysis of clinical presentations, including extramedullary involvement and eosinophilia.
Main Results:
- Heterogeneous presentations including leukemia, lymphoma, myeloid sarcoma, and MDS.
- Common features: extramedullary involvement (58%), eosinophilia (67%), and multilineage involvement.
- No FLT3 or KIT mutations detected in analyzed cases.
- Patients showed response to chemotherapy, hypomethylating agents, FLT3 inhibitors, and stem cell transplant.
Conclusions:
- M/LN with FLT3 rearrangement exhibit characteristics similar to M/LN-eo with PDGFRA, PDGFRB, FGFR1, and PCM1/JAK2 rearrangements.
- Frequent eosinophilia and multilineage involvement are key features.
- Kinase inhibitors may offer therapeutic benefits for these neoplasms.
