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Low mRNA expression of the apoptosis‐related genes CASP3 , CASP8 , and FAS is associated with low induction treatment response in childhood acute lymphoblastic leukemia (ALL)
Author(s) -
Mata Juliana F.,
Silveira Vanessa S.,
Mateo Elvis C.,
Cortez Maria A.A.,
Queiroz Rosane G.P.,
Yunes José Andrés,
Lee Maria Lúcia M.,
Toledo Sílvia R.C.,
Petrilli Antonio Sérgio,
Brandalise Silvia R.,
Tone Luiz G.,
Scrideli Carlos A.
Publication year - 2010
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.22463
Subject(s) - medicine , apoptosis , gene expression , gene , white blood cell , real time polymerase chain reaction , oncology , andrology , immunology , biology , genetics
Background Defects in apoptosis signaling have been considered to be responsible for treatment failure in many types of cancer, although with controversial results. The objective of the present study was to assess the expression profile of key apoptosis‐related genes in terms of clinical and biological variables and of the survival of children with acute lymphoblastic leukemia (ALL). Procedure The levels of mRNA expression of the apoptosis‐related genes CASP3 , CASP8 , CASP9 , FAS , and BCL2 were analyzed by quantitative real‐time PCR in consecutive samples from 139 consecutive children with ALL at diagnosis treated by the Brazilian protocol (GBTLI‐ALL 99). Gene expression levels and clinical and biological features were compared by the Mann–Whitney test. Event‐free survival (EFS) was calculated by Kaplan–Meier plots and log‐rank test. Results A significant correlation was detected between CASP3 , CASP8 , CASP9 , and FAS expression levels ( P < 0.01) in ALL samples. Higher levels of BCL2 were significantly associated with white blood cell (WBC) count <50,000/mm 3 at diagnosis ( P = 0.01) and low risk group classification ( P = 0.008). Lower expression levels of CASP3, CASP8 and FAS gene were associated with a poor response at day 7 according the GBTLI‐ALL 99 protocol ( P = 0.03, P = 0.02 and P = 0.008, respectively). There was a relationship between FAS gene expression lower than the 75th percentile and lower 5‐year EFS ( P = 0.02). Conclusion These findings suggest an association between lower expression levels of the pro‐apoptotic genes and a poor response to induction therapy at day 7 and prognosis in childhood ALL. Pediatr Blood Cancer 2010;55:100–107. © 2010 Wiley‐Liss, Inc.