Serine-Threonine Protein Kinases CK1, CK2 and GSK3 in Normal and Malignant Haematopoiesis

Cellular protein kinases (PKs) have critical roles in regulating the hallmarks of cancer (autonomous cell growth, resistance to antigrowth signals, unlimited replication, neoangiogenesis, tissue invasion and metastasis). Consequently, a strong rationale drives those therapeutic strategies aimed at targeting PKs to achieve tumour regression. Haematological malignancies have been at the forefront in this field of investigation, as major successes with the use of PKs inhibitors have been obtained in the therapy of some types of leukaemia. We will herein review the established and potential roles of three serine-threonine PKs, CK1, CK2 and GSK3 in normal and malignant haematopoiesis. These PKs regulate a multitude of cellular processes, are either over-expressed or hyper-activated in leukaemia, multiple myeloma and lymphoma cells and are essential for cell survival and resistance to apoptosis through their interaction with critical signal transduction pathways. However, the knowledge of their function in normal and malignant haematopoiesis is only at the beginning. Consequently, a more precise description of these “druggable” kinases specifically in blood cells, which is a prerequisite to rationally develop targeted therapeutic approaches, will necessarily be achieved through the use of molecular, genetic and animal experimental models.