TY - JOUR
T1 - A prognostic model for survival in chronic lymphocytic leukaemia based on p53 expression
AU - Giles, Francis J.
AU - Bekele, B. Nebiyou
AU - O'Brien, Susan
AU - Cortes, Jorge E.
AU - Verstovsek, Srdan
AU - Balerdi, Maria
AU - Yared, Marwan
AU - Zhou, Xian
AU - Kantarjian, Hagop M.
AU - Keating, Michael J.
AU - Thall, Peter
AU - Albitar, Maher
PY - 2003/5
Y1 - 2003/5
N2 - As the abnormal expression of p53 protein is prognostically significant in some human cancers, its significance in patients with B-cell chronic lymphocytic leukaemia (CLL) was assessed. Two investigators evaluated the percentage of bone marrow mononuclear cells that stained for p53, using biopsies stained with anti-p53 monoclonal antibody (DO-7), and graded the degree of staining (0, +, ++, +++). Samples from a cohort of 90 patients with CLL were studied (median age 60 years, range 30-89 years; 57 patients were (63%) previously untreated, 22 patients (24%) had received one or two prior regimens, 11 patients had received (12%) three to seven regimens. The overall percentage of cells positive for p53 staining was a median of 43 (range 1-88). No investigator effect was detected either in overall percentage cells rated p53 positive or on the degree of staining (Pearson's correlation coefficient 0.980, P-value <0.001). A Cox proportional hazards model showed that the percentage of ++ and +++ p53-positive cells correlated with various prognostic factors in CLL (P < 0.0001). A multivariate model incorporating prior therapy, Rai stage, beta2 microglobulin (β2M) and p53 expression showed that only the percentage of p53-positive cells and β2M were predictive of survival, and enabled the development of a highly predictive model of survival based on these two parameters.
AB - As the abnormal expression of p53 protein is prognostically significant in some human cancers, its significance in patients with B-cell chronic lymphocytic leukaemia (CLL) was assessed. Two investigators evaluated the percentage of bone marrow mononuclear cells that stained for p53, using biopsies stained with anti-p53 monoclonal antibody (DO-7), and graded the degree of staining (0, +, ++, +++). Samples from a cohort of 90 patients with CLL were studied (median age 60 years, range 30-89 years; 57 patients were (63%) previously untreated, 22 patients (24%) had received one or two prior regimens, 11 patients had received (12%) three to seven regimens. The overall percentage of cells positive for p53 staining was a median of 43 (range 1-88). No investigator effect was detected either in overall percentage cells rated p53 positive or on the degree of staining (Pearson's correlation coefficient 0.980, P-value <0.001). A Cox proportional hazards model showed that the percentage of ++ and +++ p53-positive cells correlated with various prognostic factors in CLL (P < 0.0001). A multivariate model incorporating prior therapy, Rai stage, beta2 microglobulin (β2M) and p53 expression showed that only the percentage of p53-positive cells and β2M were predictive of survival, and enabled the development of a highly predictive model of survival based on these two parameters.
KW - Chronic lymphocytic leukaemia
KW - Immunoperoxidase
KW - Prognosis
KW - Survival
KW - p53
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U2 - 10.1046/j.1365-2141.2003.04306.x
DO - 10.1046/j.1365-2141.2003.04306.x
M3 - Article
C2 - 12752098
AN - SCOPUS:0037716441
SN - 0007-1048
VL - 121
SP - 578
EP - 585
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 4
ER -