Gene Set: FLOTHO_PEDIATRIC_ALL_THERAPY_RESPONSE_DN

Standard name FLOTHO_PEDIATRIC_ALL_THERAPY_RESPONSE_DN
Systematic name M4866
Brief description Down-regulated genes significantly associated with positive minimal residual disease (MRD) on day 46 after chemotherapy treatment of children with acute lymphoblastic leukemia (ALL).
Full description or abstract In childhood acute lymphoblastic leukemia (ALL), early response to treatment is a powerful prognostic indicator. To identify genes associated with this response, we analyzed gene expression of diagnostic lymphoblasts from 189 children with ALL and compared the findings with minimal residual disease (MRD) levels on days 19 and 46 of remission induction treatment. After excluding genes associated with genetic subgroups, we identified 17 genes that were significantly associated with MRD. The caspase 8-associated protein 2 (CASP8AP2) gene was studied further because of its reported role in apoptosis and glucocorticoid signaling. In a separate cohort of 99 patients not included in the comparison of gene expression profiles and MRD, low levels of CASP8AP2 expression predicted a lower event-free survival (P = .02) and a higher rate of leukemia relapse (P = .01) and were an independent predictor of outcome. High levels of CASP8AP2 expression were associated with a greater propensity of leukemic lymphoblasts to undergo apoptosis. We conclude that measurement of CASP8AP2 expression at diagnosis offers a means to identify patients whose leukemic cells are highly susceptible to chemotherapy. Therefore, this gene is a strong candidate for inclusion in gene expression arrays specifically designed for leukemia diagnosis.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 16627760   Authors: Flotho C,Coustan-Smith E,Pei D,Iwamoto S,Song G,Cheng C,Pui CH,Downing JR,Campana D
Exact source Table 1: Genes underexpressed in MRD+
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform AFFY_HG_U133
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