Pre-BCR expression predicts sensitivity to SYK inhibition in B-cell acute lymphoblastic leukemia

Introduction: Recent studies have suggested SYK as target for the treatment of pre-BCR+ B-ALL but whether pre-BCR status constitutes the only predictor for sensitivity to SYK inhibition in B-ALL is discussed controversially. Methods: We employed a comparative approach of pre-BCR knockout and pharmacologic inhibition of pre-BCR signaling with SYK inhibitors to dissect the requirements for the SYK-dependent survival of B-ALL cells. Results: Pre-BCR+ ALL requires constitutive signals from the pre-BCR and SYK for proliferation and survival. These signals involve the pre-BCR-dependent activation of SYK and PI3K, resu…