Daunorubicin induces Cysteine‐rich protein 61 to decreases the Chemosensitivity through the ATM/NF-κB pathway in B-acute lymphoblastic leukemia

Background: Acute lymphoblastic leukemia（ALL）is the second most common hematologic malignancy worldwide with B-acute lymphoblastic leukemia（B-ALL）accounting for 70%-80%. Cysteine‐rich protein 61 (Cyr61), a potential tumor-promoting factor, is increased in both serum and bone marrow of B-ALL patients in our previous study. We aimed to elucidate the role of Cyr61 in B-ALL as well as to explore the source of Cyr61 in the bone marrow of B-ALL patients.Methods: The human B-ALL cell line Nalm-6 was used. Cyr61 expression levels were measured by using quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and western blot analysis. The biological functions of Cyr61 in regulating B-ALL cell chemosensitivity to DNR and VCR was detected by cell viability assay and flow cytometry analysis. The production mechanisms of Cyr61 in the bone marrow were measured by qRT-PCR and western blot analysis.Results: Knockdown of Cyr61 increased the chemosensitivity of Nalm-6 cells to DNR and VCR, and overexpression of Cyr61 decreased the chemosensitivity of Nalm-6 cells to DNR and VCR. Mechanistically, we found that Cyr61 attenuated chemotherapeutic drug-induced apoptosis by the upregulation of Bcl-2. Importantly, Cyr61 can be up-regulated by the chemotherapeutic drug DNR through the ATM-dependent NF-κ B pathway, however, VCR has no effect on the expression of Cyr61 in B-All cells.Conclusions: In conclusion, our study revealed that DNR can induce the production of Cyr61 in B-ALL cells; further, increasing Cyr61 decreased the chemosensitivity of B-ALL cells to chemotherapeutic drugs. Thus, targeting Cyr61 may be a promising therapeutic strategy to increase the chemotherapy sensitivity in patients with B-ALL.