Here, we provide an in vitro-based study, which aimed to illustrate the application of entospletinib as a specific SYK inhibitor on pre- and pro-B-acute lymphoblastic leukemia cell lines, in order to further demonstrate a possible application in a subset of precursor B-ALL and, moreover, to elucidate the underlying diverging acting modes. This evidence concerns the gene SYK and acute lymphoblastic leukemia.