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Published on: September 20, 2016
FLT3 mutations in myelodysplastic syndrome and chronic myelomonocytic leukemia
Naval Daver1, Paolo Strati, Elias Jabbour
1Department of Leukemia and Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, USA.
Abstract:
FMS-like tyrosine kinase III (FLT3) mutations occur in one-third of acute myeloid leukemia (AML) patients and predict poor outcome. The incidence and impact of FLT3 in myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) is unknown. We conducted a retrospective review to identify WHO MDS and CMML patients with FLT3 mutations at diagnosis. A total of 2,119 patients with MDS and 466 patients with CMML were evaluated at MD Anderson between 1997 and 2010. Of these, FLT3 mutation analysis was performed on 1,232 (58%) MDS and 302 (65%) CMML patients. FLT3 mutations were identified in 12 (0.95%) MDS patients: 9 (75%) had FLT3-ITD mutation and 3 had FLT3-tyrosine kinase domain (TKD) mutation. MDS patients with FLT3 mutations were younger (P = 0.02) and presented as RAEB (P = 0.03) more frequently. Median overall survival (OS) for FLT3-mutated MDS patients was 19.0 months versus 16.4 months for FLT3-nonmutated MDS patients (P = 0.08). FLT3 mutations were identified in 13 (4.3%) CMML patients: 8 had FLT3-ITD mutation and 5 had FLT3-TKD mutation. There were no significant differences in demographic and disease characteristics among CMML patients with and without FLT3 mutations. Median OS for FLT3-mutated CMML patients was 10.8 months versus 21.3 months for FLT3-nonmutated CMML patients (P = 0.12). FLT3 occurs in MDS and CMML at a lower frequency than AML and does not predict poor outcome.
Insights
FMS-like tyrosine kinase III (FLT3) mutations are less common in myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) than in acute myeloid leukemia (AML). These FLT3 mutations do not appear to predict a poor outcome in MDS or CMML patients.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- FMS-like tyrosine kinase III (FLT3) mutations are prevalent in acute myeloid leukemia (AML), correlating with poor prognosis.
- The incidence and prognostic significance of FLT3 mutations in myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) remain largely uncharacterized.
Purpose of the Study:
- To investigate the frequency and clinical impact of FLT3 mutations at diagnosis in patients with MDS and CMML.
- To compare the characteristics and outcomes of FLT3-mutated versus FLT3-nonmutated MDS and CMML cohorts.
Main Methods:
- Retrospective review of 2,119 MDS and 466 CMML patients diagnosed between 1997 and 2010.
- FLT3 mutation analysis (including FLT3-ITD and FLT3-TKD) performed on 1,232 MDS and 302 CMML patients.
- Comparison of demographic, disease characteristics, and overall survival (OS) between mutated and non-mutated groups.
Main Results:
- FLT3 mutations were identified in 0.95% of MDS patients (12/1232) and 4.3% of CMML patients (13/302).
- MDS patients with FLT3 mutations were younger and more frequently presented as refractory anemia with excess blasts (RAEB).
- No significant differences in overall survival were observed for FLT3-mutated versus non-mutated MDS (19.0 vs 16.4 months, P=0.08) or CMML (10.8 vs 21.3 months, P=0.12) patients.
Conclusions:
- FLT3 mutations occur at a lower frequency in MDS and CMML compared to AML.
- FLT3 mutations do not appear to be a negative prognostic marker in MDS or CMML.
- Further research may elucidate the specific role of FLT3 in these myeloid malignancies.
