Therapeutic potential of spleen tyrosine kinase inhibition for treatment of high-risk precursor B-cell acute lymphoblastic leukemia

ABSTRACT: This study revealed pathogenic role of pre-BCR-independent SYK activation in high-risk B-ALL. Intensified and central nervous system (CNS)-directed chemotherapy has significantly improved outcomes for pediatric B-acute lymphoblastic leukemia (B-ALL), but confers significant late-effect morbidities. Moreover, many patients suffer relapses, underscoring the need to develop novel, molecularly targeted B-ALL therapies. Using a mouse model, we showed that leukemic B-cells require pre-B-cell receptor (pre-BCR)-independent spleen tyrosine kinase (SYK) signaling in vivo. In diagnostic samples from human B-ALL patients, SYK and downstream targets were phosphorylated regardless of pre-BCR expression or genetic subtype. Two small molecule SYK inhibitors, fostamatinib and BAY61-3606, attenuated growth

ORGANISM(S): Mus musculus

SUBMITTER: Paul Kowalski 

PROVIDER: E-GEOD-56345 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress