Overexpression of PTP4A3 in ETV6-RUNX1 acute lymphoblastic leukemia

- PTP4A3 is overexpressed in specific subtypes of acute lymphoblastic leukemia.
- ETV6-RUNX1 and BCR-ABL1 subtypes show strongest expression of PTP4A3.
- MLL-rearranged leukemias exhibit low level of PTP4A3 expression.
- PTP4A3 is regulated by the ETV6-RUNX1 fusion.
- Inhibition or knockdown of PTP4A3 has no marked effect on leukemia cell viability.

Cell signalling, which is often derailed in cancer, is a network of multiple interconnected pathways with numerous feedback mechanisms. Dynamics of cell signalling is intimately regulated by addition and removal of phosphate groups by kinases and phosphatases. We examined expression of members of the PTP4A family of phosphatases across acute leukemias. While expression of PTP4A1 and PTP4A2 remained relatively unchanged across diseases, PTP4A3 showed marked overexpression in ETV6-RUNX1 and BCR-ABL1 subtypes of precursor B cell acute lymphoblastic leukemia. We show that PTP4A3 is regulated by the ETV6-RUNX1 fusion, but noticed no marked impact on cell viability either after PTP4A3 silencing or treatment with a PTP4A3 inhibitor. Regulation of PTP4A3 expression is altered in specific subgroups of acute leukemias and this is likely brought about by expression of the aberrant fusion genes.