Acute lymphoblastic leukemia (ALL) is an aggressive malignancy of developing lymphocytes. Despite outstanding overall cure rates, patients with the refractory or relapsed disease have a poor prognosis. 1 In order to improve treatments for these high-risk (HR)-ALL patients, it is critical to gain an in-depth understanding of the disease pathogenesis. The enhanced expression of the protein kinase CK2 gene and proto-oncogene MYC are common in T cell ALL (T-ALL) and B cell ALL (B-ALL). 2-6 CK2 is a constitutively active serine/threonine kinase composed of two catalytic (a or a') and two regulatory (ß) subunits that are overexpressed in a broad spectrum of human cancers. 7 Despite the demonstrated antileukemic efficacy of CK2 inhibitors, 8 how CK2 contributes to HR-ALL development remains incompletely understood. Here we utilized transgenic zebrafish models to elaborate the multifaceted role of CK2 in HR-ALL pathogenesis, providing therapeutic implications for this stubborn disease.

Overexpression of the CK2a subunit under the immunoglobulin gene promoter induces low penetrance of T-cell lymphomas in a murine model. 9 In order to further understand the oncogenic potential of CK2 in T and B lineages, we generated transgenic zebrafish that overexpress the wild-type or the kinase-dead version (K68M) of the human CK2a gene in T and B cells through the zebrafish tyrosine kinase gene (lck) promoter. 2, 10 Western blotting analysis revealed elevated expression of CK2a in transgenic CK2 fish, compared to age-matched wild-type