Genes contributing to minimal residual disease in childhood acute lymphoblastic leukemia:: prognostic significance of CASP8AP2

被引:82
作者
Flotho, Christian
Coustan-Smith, Elaine
Pei, Deqing
Iwamoto, Shotaro
Song, Guangchun
Cheng, Cheng
Pui, Ching-Hon
Downing, James R.
Campana, Dario
机构
[1] St Jude Childrens Res Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA
[2] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA
[3] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA
[4] Univ Tennessee, Ctr Hlth Sci, Coll Med, Memphis, TN 38163 USA
关键词
D O I
10.1182/blood-2006-01-0322
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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收藏
页码:1050 / 1057
页数:8
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