Serial studies of methylation of CDKN2B and CDKN2A in relapsed acute promyelocytic leukaemia treated with arsenic trioxide.
Ninety consecutive patients with acute promyelocytic leukaemia were investigated for promoter methylation of CDKN2B (alias p15) and CDKN2A (alias p16) in disease relapse and progression. CDKN2B methylation was significantly more frequent at first relapse (30/36, 83%) than at presentation (48/77, 62%) (P=0.025), while CDKN2A methylation appeared unaffected. Both acquisition and loss of CDKN2B methylation happened at relapse, with acquisition more frequent. No significant increase in CDKN2B and CDKN2A methylation occurred at more advanced relapses. At first or subsequent relapses, owing to highly effective salvage by arsenic trioxide, CDKN2B methylation did not impact on event-free survival or overall survival.
Au
Wing-Yan
WY
Department of Medicine, University of Hong Kong, Hong Kong.
Fung
Alvin T
AT
Ma
Edmond S
ES
Chan
Cheuk-Hung
CH
Wong
Kit-Fai
KF
Chim
Chor-Sang
CS
Liang
Raymond H
RH
Kwong
Yok-Lam
YL
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use*; D016022:Case-Control Studies; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D008745:Methylation; D018365:Neoplasm, Residual / Q000378:metabolism*; D010087:Oxides / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D001152:Arsenicals; C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D010087:Oxides; D000077237:Arsenic Trioxide