Linking the SUMO protease SENP5 to neutrophil differentiation of AML cells

• SENP5 is repressed in clinical AML when compared to healthy neutrophil samples.
• SENP5 expression increases during ATRA-induced differentiation of APL blasts.
• Knocking down SENP5 decreases ATRA-induced granulocytic differentiation.
• Knocking down SENP5 reduces cell viability upon differentiation.

In an mRNA profiling screen performed to unveil novel mechanisms of leukemogenesis, we found that the sentrin-specific protease 5 (SENP5) was significantly repressed in clinical acute myeloid leukemia when compared to healthy neutrophil samples. SENP5 is an enzyme that targets and cleaves small ubiquitin-like modifier (SUMO) residues from SUMOylated proteins. Further investigation with AML neutrophil differentiation cell models showed increased SENP5 expression upon induction of differentiation; in contrast, knocking down SENP5 resulted in significantly attenuated neutrophil differentiation. Our results support a new role of SENP5 in AML pathology, and in particular in the neutrophil differentiation of myeloid leukemic cells.