TYK2 Activating Alterations in Acute Lymphoblastic Leukemia: Novel Driver Oncogenes with Potential Avenues for Precision Medicine?

Author(s): Paniz Tavakoli Shirazi, Laura N Eadie, Susan L Heatley, Deborah L White

Utilization of Next Generation Sequencing (NGS) and advances in genomic profiling have led to identification of new lesions in acute lymphoblastic leukemia (ALL) cases. TYK2 alterations are among those that warrant an in-depth characterization of the underlying mechanisms that result in leukemogenesis, targetability potential and drug response. The current literature around the functional significance and clinical importance of these alterations in driving hematological cancer (in particular, leukemia) is limited. This review focuses on recent findings demonstrating the leukemogenic potential of TYK2 alterations. Specifically, the molecular consequences of aberrant TYK2 levels are detailed and the effects of TYK2 deficiency or dysregulated activation are explored in carcinogenesis and leukemogenesis. In addition, the functional role of TYK2 in JAK/STAT signaling, possible cross talk to other cancer-related pathways and overarching avenues for pharmacological intervention in TYK2-altered ALL are also described.