Acute Myeloid Leukemia Case Harboring Unusual FLT3 Variant: Somatic vs Germline?

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• FLT3 mutations are established prognostic and predictive markers in acute myeloid leukemia (AML).
• Distinguishing between somatic and germline mutations is critical for accurate patient management and treatment selection.

Purpose of the Study:

• To report a rare case of FLT3 germline variant in a patient with relapsed AML.
• To highlight the importance of identifying germline mutations for potential targeted therapy eligibility.

Main Methods:

• Case report of a 57-year-old female patient with relapsed AML.
• Targeted next-generation sequencing (NGS) for mutation identification.
• Simultaneous tumor/germline sequencing to determine mutation origin.

Main Results:

• The patient presented with AML harboring IDH2, ASXL1, and DNMT3A mutations.
• Post-allogeneic hematopoietic stem cell transplant relapse occurred.
• A novel missense variant, c.2440G > T (p.A814S), was identified in the FLT3 tyrosine kinase domain.
• The variant was confirmed as a germline mutation.

Conclusions:

• Rare FLT3 germline variants can occur in relapsed AML.
• Germline mutation identification is essential for assessing eligibility for FLT3 inhibitors.
• Simultaneous tumor/germline sequencing aids in understanding disease pathogenesis and guiding therapy.