Blood: IKAROS and CK2 regulate high-risk B-ALL BCL-XL expression and chemotherapy sensitivity

High-risk B-cell acute lymphoblastic leukemia (B-ALL) is an invasive disease characterized by chemotherapy resistanceA common feature of high-risk B-ALL is the loss of function of the tumor suppressor IKAROS (encoded by the IKZF1 gene)in this study,Song et alfound that the IKAROS regulated the expression of the BCL2L1 gene (codebcl-xl protein) in humanb-ALLfunctional acquiring and functional loss experiments showed that IKAROS combined with BCL2L1 promoters to recruit histones deacetylase HDAC1 and inhibit the expression of BCL2L1 through chromatin remodelingIn leukemia, cancer-causing tyrosinkinase II (CK2) is highly expressed in B-ALL, impairing the function of IKAROSCK2 phosphorylation reduces the BCL2L1 starter combined with IKAROS and raised HDAC1This led to the loss of BCL2L1 expression inhibition and the increase of BCL-XL expressionIncreased BCL-XL and/or CK2 expression, as well as decreased IKAROS expression, were associated with drug resistance in dojobi star therapyThe binding of IKAROS and BCL2L1 promoters can be increased with the specific inhibitor CX-4945 inhibition of CK2, and the inhibition of BCL2L1 mediated by IKAROS can be enhanced in B-ALLTHE CX-4945 TREATMENT ENHANCES B-ALL'S SENSITIVITY TO DOJOBI STARS AND REVERSES B-ALL'S RESISTANCE TO DOJOBI STARSThe combination of CX-4945 and dojostar combination therapy showed synergistic therapeutic effects in both in vitro and in preclinical models of high-risk B-ALL, the results reveal a new signal network that is involved in regulating chemotherapy resistance to leukemiaThe data of this study lay the foundation for the clinical testing of targeted therapy for the treatment of malignant tumors of the blood system in combination with CK2 inhibitor CX-4945