Page 243 - 2021_05-Haematologica-web

Letters to the Editor
regression, stable disease, and progression.11 By 4 weeks post-withdrawal of 4HT, approximately 35% of MYC-ER fish and approximately 50% of MYC-ER;CK2αwt fish had already exhibited complete tumor regression (Figure 3B). We found that there were no statistically significant differences between MYC-ER versus MYC-ER;CK2αwt fish for the changes of tumor status at both 4 and 8 weeks post 4HT removal (Figure 3C and data not shown). These results demonstrate that CK2 overexpression alone cannot substitute for aberrant MYC activity in maintaining the established disease.
In this study, we elaborated on the contribution of CK2 to different stages of HR-ALL development using the tamoxifen-regulated zebrafish model of MYC-induced ALL. Our data show that the kinase activity of CK2 pro- motes both the onset and progression of T- and B-ALL in the presence of aberrant MYC activation, but cannot maintain the disease upon MYC inactivation through the removal of 4HT. When MYC-ER fish are treated with 4HT to activate MYC at a later stage of development, these fish can no longer develop leukemia, indicating a temporal restriction of MYC-induced lymphocyte trans-
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Figure 2. CK2α overexpression overcomes temporal restriction of MYC-induced lymphocyte transformation and induces leukemia at the later stage of devel- opment. (A) Diagram of the experimental design. (B) Thymic fluorescence in MYC-ER and MYC-ER;CK2αwt zebrafish that were raised in 129 nM 4-hydroxyta- moxifen (4HT) beginning at 30 dpf. (C) Kaplan-Meier analysis of tumor-free fish based on genotype (P<0.0001; n=18 for MYC-ER and n=34 for MYC-ER;CK2αwt fish). Statistical analysis was performed using the log-rank test and scale bars =1 mm.
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