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Published on: June 6, 2025
FES kinases are required for oncogenic FLT3 signaling
1INSERM, UMR 891, Centre de Recherche en Cancérologie de Marseille, Laboratoire de Signalisation, Hématopoïèse et Mécanismes de l'Oncogenèse, Marseille, France.
Leukemia
|January 30, 2010
Summary
Both FES and FER kinases are activated in acute myeloid leukemia (AML) and are critical for FLT3-ITD signaling. These non-receptor tyrosine kinases mediate essential, non-redundant functions in AML cell survival and proliferation.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Non-receptor tyrosine kinases Feline Sarcoma (FES) and FEs Related (FER) are activated by cell surface receptors in hematopoietic cells.
- The role of FES and FER in human pathology, particularly in acute myeloid leukemia (AML), is not well understood.
- Previous research indicated FES, but not FER, is crucial for oncogenic KIT receptor signaling.
Purpose of the Study:
- To investigate the activation and functional significance of FES and FER kinases in acute myeloid leukemia (AML).
- To determine the role of FES and FER in signaling pathways relevant to AML, specifically downstream of FLT3-ITD.
- To elucidate the distinct contributions of FES and FER to AML cell proliferation, survival, and cell cycle progression.
Main Methods:
- Analysis of FES and FER kinase activation in primary AML blasts and AML cell lines.
- Investigating the dependence of FES and FER activation on FLT3 signaling in AML cell lines with constitutively active FLT3 mutants.
- Assessing the impact of FES and FER on FLT3-ITD signaling, cell proliferation, survival, and cell cycle progression in relevant AML models.
Main Results:
- Both FES and FER kinases are activated in primary AML blasts and AML cell lines.
- FES and FER activation is dependent on FMS-like tyrosine kinase 3 (FLT3) in cell lines with activating FLT3 mutations.
- FES and FER are critical for FLT3-internal tandem duplication (ITD) signaling, cell proliferation, survival, and cell cycle progression in AML cell lines, with FER supporting cell cycle transitions and FES supporting cell survival.
Conclusions:
- FES and FER kinases are activated downstream of FLT3-ITD in acute myeloid leukemia.
- FES and FER play essential, non-redundant roles in mediating FLT3-ITD signaling, crucial for AML cell proliferation and survival.
- Targeting FES and FER may represent a potential therapeutic strategy for AML patients with FLT3-ITD mutations.
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