A screening of donated chemical probes to identify novel therapeutic options for childhood AML

Despite intensive treatment regimens, the survival rate for children with acute myeloid leukemia (AML) has not improved beyond 70%. Recently, targeted therapies and small molecules have emerged as promising alternative treatment options. To explore these options, we conducted a screening of 105 small molecules in four different AML cell lines, followed by a screening of promising compounds in patient-derived cells of childhood AML. In addition to HDAC and BET inhibition, we found that inhibition of Cdc2-like kinases (CLKs) effectively reduced cell viability in both cell lines and patient-derived cells. CLKs play a key role in splicing. Alternative splicing isassociated with solid andhematological malignancies through mutations in splicing factors and alterations in the expressionlevels of splicing regulatory factors. This gives us reason to believe that CLK inhibition may represent apromising new therapeutic option for pediatric AML.

Publication History

Article published online:
12 May 2023