TY - JOUR
T1 - Common polymorphism G(-248)A in the promoter region of the bax gene results in significantly shorter survival in patients with chronic lymphocytic leukaemia once treatment is initiated
AU - Starczynski, J
AU - Pepper, C
AU - Pratt, Guy
AU - Hooper, L
AU - Thomas, A
AU - Milligan, Donald
AU - Bentley, P
AU - Fegan, Christopher
PY - 2005/1/31
Y1 - 2005/1/31
N2 - Purpose
Chronic lymphocytic leukemia (CLL) is characterized by the development of drug resistance, The underlying biologic and genetic reasons for this resistance are complex, but the bcl-2 gene family seems to play a critical role. This retrospective study assessed the clinical impact of a common single nucleotide polymorphism of the pro-apoptotic bax gene in patients with chronic lymphocytic leukemia.
Patients and Methods
The frequency of the novel polymorphism, G(-248)A, in the promoter region of the bax gene and bax protein expression was assessed in 203 CLL patients. The results were correlated with clinical outcome.
Results
The polymorphism was found in 23% of the CLL cohort and 15% of normal controls with no significant difference in allele frequency between the two groups (P = .15). It was associated with lower Bax protein expression and a shorter overall survival, especially in the treated patient group (P = .03). Furthermore, the adverse impact of the polymorphism was accentuated when comparing survival from the date of first treatment rather than diagnosis (P = .012). No significant difference in age at diagnosis, stage of disease at presentation, lymphocyte doubling time, time to first treatment, or progression-free survival were observed.
Conclusion
The presence of this single nucleotide polymorphism in CLL critically influences the response to treatment and overall survival. Given the relatively high prevalence of this polymorphism in the normal population, further prospective studies in CLL and other human malignancies are indicated.
AB - Purpose
Chronic lymphocytic leukemia (CLL) is characterized by the development of drug resistance, The underlying biologic and genetic reasons for this resistance are complex, but the bcl-2 gene family seems to play a critical role. This retrospective study assessed the clinical impact of a common single nucleotide polymorphism of the pro-apoptotic bax gene in patients with chronic lymphocytic leukemia.
Patients and Methods
The frequency of the novel polymorphism, G(-248)A, in the promoter region of the bax gene and bax protein expression was assessed in 203 CLL patients. The results were correlated with clinical outcome.
Results
The polymorphism was found in 23% of the CLL cohort and 15% of normal controls with no significant difference in allele frequency between the two groups (P = .15). It was associated with lower Bax protein expression and a shorter overall survival, especially in the treated patient group (P = .03). Furthermore, the adverse impact of the polymorphism was accentuated when comparing survival from the date of first treatment rather than diagnosis (P = .012). No significant difference in age at diagnosis, stage of disease at presentation, lymphocyte doubling time, time to first treatment, or progression-free survival were observed.
Conclusion
The presence of this single nucleotide polymorphism in CLL critically influences the response to treatment and overall survival. Given the relatively high prevalence of this polymorphism in the normal population, further prospective studies in CLL and other human malignancies are indicated.
UR - http://www.scopus.com/inward/record.url?scp=14944346868&partnerID=8YFLogxK
U2 - 10.1200/JCO.2005.02.192
DO - 10.1200/JCO.2005.02.192
M3 - Article
C2 - 15735127
SN - 1527-7755
VL - 23
SP - 1514
EP - 1521
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
ER -