Transcription profiling of human T-ALL samples to investigate synergistic interaction of gamma-secretase inhibitor therapy and glucocorticoids

ABSTRACT: Glucocorticoids are an essential component of the treatment of lymphoid malignancies and resistance to glucocorticoid therapy constitutes a prominent clinical problem in relapsed and refractory lymphoblastic leukemias. Constitutively active NOTCH signaling is involved in the pathogenesis of over 50% of T-cell lymphoblastic leukemia (T-ALL) which harbor activating mutations in the NOTCH1 gene. Aberrant NOTCH1 signaling has been shown to protect normal thymocytes from glucocorticoid induced cell death. Here we analyzed the interaction of glucocorticoid therapy with inhibition of NOTCH signaling in the treatment of T-ALL. Gamma-secretase inhibitors (GSI), which block the activation of NOTCH receptors, amplified the transcriptional changes induced by glucocorticoid treatment, including glucoc

ORGANISM(S): Homo sapiens

SUBMITTER: Adolfo Ferrando 

PROVIDER: E-GEOD-7067 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress