TY - JOUR
T1 - Residual DNA methylation at remission is prognostic in adult Philadelphia chromosome-negative acute lymphocytic leukemia
AU - Yang, Hui
AU - Kadia, Tapan
AU - Xiao, Lianchun
AU - Bueso-Ramos, Carlos E.
AU - Hoshino, Koyu
AU - Thomas, Deborah Ann
AU - O'Brien, Susan
AU - Jabbour, Elias
AU - Pierce, Sherry
AU - Rosner, Gary L.
AU - Kantarjian, Hagop M.
AU - Garcia-Manero, Guillermo
PY - 2009/2/26
Y1 - 2009/2/26
N2 - Pretreatment aberrant DNA methylation patterns are stable at time of relapse in acute lymphocytic leukemia (ALL). We hypothesized that the detection of residual methylation alterations at the time of morphologic remission may predict for worse prognosis. We developed a realtime bisulfite polymerase chain reaction assay and analyzed the methylation levels of p73, p15, and p57 KIP2 at the time of initial remission in 199 patients with Philadelphia chromosome-negative and MLL- ALL. Residual p73 methylation was detected in 18 (9.5%) patients, p15 in 33 (17.4%), and p57 KIP2 in 7 (3.7%); 140 (74%) patients had methylation of 0 genes and 48 (25%) of more than or equal to 1 gene. In 123 (65%) patients, matched pretreatment samples were also studied and compared with remission ones: in 82 of those with initial aberrant methylation of at least one gene, 59 (72%) had no detectable methylation at remission and 23 (28%) had detectable residual methylation. By multivariate analysis, the presence of residual p73 methylation was associated with a significant shorter duration of first complete remission (hazard ratio = 2.68, P = .003) and overall survival (hazard ratio = 2.69, P = .002). In conclusion, detection of epigenetic alterations allows the identification of patients with ALL with standard risk but with poor prognosis.
AB - Pretreatment aberrant DNA methylation patterns are stable at time of relapse in acute lymphocytic leukemia (ALL). We hypothesized that the detection of residual methylation alterations at the time of morphologic remission may predict for worse prognosis. We developed a realtime bisulfite polymerase chain reaction assay and analyzed the methylation levels of p73, p15, and p57 KIP2 at the time of initial remission in 199 patients with Philadelphia chromosome-negative and MLL- ALL. Residual p73 methylation was detected in 18 (9.5%) patients, p15 in 33 (17.4%), and p57 KIP2 in 7 (3.7%); 140 (74%) patients had methylation of 0 genes and 48 (25%) of more than or equal to 1 gene. In 123 (65%) patients, matched pretreatment samples were also studied and compared with remission ones: in 82 of those with initial aberrant methylation of at least one gene, 59 (72%) had no detectable methylation at remission and 23 (28%) had detectable residual methylation. By multivariate analysis, the presence of residual p73 methylation was associated with a significant shorter duration of first complete remission (hazard ratio = 2.68, P = .003) and overall survival (hazard ratio = 2.69, P = .002). In conclusion, detection of epigenetic alterations allows the identification of patients with ALL with standard risk but with poor prognosis.
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U2 - 10.1182/blood-2008-02-141002
DO - 10.1182/blood-2008-02-141002
M3 - Article
C2 - 19109226
AN - SCOPUS:61849117834
SN - 0006-4971
VL - 113
SP - 1892
EP - 1898
JO - Blood
JF - Blood
IS - 9
ER -