Two myeloid leukemia cases with rare FLT3 fusions

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• Genetic rearrangements involving the FMS-like tyrosine kinase 3 (FLT3) gene are uncommon in hematologic malignancies.
• Recent studies have identified FLT3 fusions in myeloid/lymphoid neoplasms with eosinophilia (MLN-eos) and chronic myeloproliferative disorders.

Observation:

• This study reports two cases of mixed myelodysplastic/myeloproliferative neoplasms (MDS/MPN) with distinct FLT3 fusions.
• The first case involved a novel MYO18A-FLT3 fusion in a patient with atypical chronic myeloid leukemia (aCML).
• The second case presented an ETV6-FLT3 fusion in a patient with chronic myelomonocytic leukemia (CMML).

Findings:

• Novel gene fusions involving FLT3 were identified in patients with MDS/MPN.
• The identified fusions were MYO18A-FLT3 and ETV6-FLT3.
• Ex vivo drug screening demonstrated sensitivity of both patient samples to FLT3 inhibitors, including quizartinib and sorafenib.

Implications:

• These findings expand the spectrum of known FLT3-associated myeloid neoplasms.
• The observed sensitivity to FLT3 inhibitors suggests a potential therapeutic strategy for patients with these rare genetic alterations.
• Further research into FLT3-driven MDS/MPN is warranted to explore targeted treatment options.