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Updated: Jun 10, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
FLT3 mutations at diagnosis and relapse in acute myeloid leukemia: cytogenetic and pathologic correlations, including
Stanley R McCormick1, Matthew J McCormick, Patricia S Grutkoski
1Department of Pathology, United Hospital, St Paul, MN 55102, USA. stan.mccormick@allina.com
Context:
Acquired mutations in the fms-like tyrosine kinase 3 gene (FLT3) adversely impact relapse risk after chemotherapy in patients with acute myeloid leukemia (AML). The FLT3 mutation status may differ at diagnosis and relapse, suggesting a potential role in chemoresistance, yet few reports have addressed the cytogenetic and pathologic correlates of FLT3 mutations in relapsed AML.
Objectives:
To determine FLT3 mutations at diagnosis and relapse in a cohort of adult patients with chemoresistant AML and to correlate mutation status with multiple variables.
Design:
We retrospectively determined FLT3 internal tandem duplication (FLT3/ITD) and FLT3 tyrosine kinase domain mutations in 50 diagnosis/relapse pairs. We correlated FLT3 status with karyotype, World Health Organization 2008 subtype, white blood cell count, biopsy cellularity, blast percentage, and the presence of invaginated ("cuplike") blast nuclei.
Results:
In 11 of 50 patients (22%) the FLT3 mutation status differed at relapse and diagnosis, with a trend toward gain of FLT3/ITD (n = 7) and loss of FLT3 tyrosine kinase domain (n = 5) mutations. FLT3-mutated AMLs correlated with the World Health Organization 2008 subtype, AML, not otherwise specified, hyperproliferative features at diagnosis and relapse, and cytogenetic evolution. FLT3-wild type AMLs correlated with the subtype AML with myelodysplasia-related changes and frequently had adverse presentation karyotypes. Cuplike blast morphology was associated with FLT3/ITD+ status and with high mutation levels. Four of 7 patients with relapse-only FLT3/ITD mutations exhibited cuplike blasts at relapse after being noncuplike at diagnosis.
Conclusions:
In addition to well-known correlates in pretreatment specimens, FLT3 mutation status has pathologic and cytogenetic significance at relapse. A shift to cuplike blast morphology at relapse may herald emergence of a previously undetected FLT3/ITD mutation.
