title: Estrogen receptor methylation is associated with improved survival in adult acute myeloid leukemia.
abstract: Estrogen receptor methylation (ERM) is a frequent molecular alteration in adult acute myeloid leukemia (AML). In this study, we sought to determine the clinical characteristics and prognostic significance of ERM in AML. ERM was determined for 268 patients who had leukemic blasts available for molecular analysis. ERM was measured by Southern blot analysis, and results were obtained for 261 patients (ages 17-69). ERM ranged from 0-99.1%, with a median of 25%. One hundred sixty patients (61%) had ERM values over 15% and were considered ERM+. In a subset of patients analyzed, ERM+ samples had markedly lower ER gene expression compared with ERM- samples. In multiple regression analyses of patient and disease characteristics at diagnosis, two factors had significant independent association with ERM: ERM decreased with increasing age (P = 0.0001) and was significantly lower in patients with French-American-British classification M4 or M5 (P = 0.0019). In regression analyses of outcome measures, ERM had no significant impact on complete remission rate after initial induction therapy. However, ERM+ patients had significantly better overall survival [OS; 18% at 6 years; 95% confidence interval (CI), 12-24% versus 9%; CI, 3-14% for ERM- patients; P = 0.022]. In multiple regression analyses, OS increased with increasing ERM (P = 0.0044). Similar results were seen for relapse-free survival (23% at 6 years; CI, 15-32% for ERM+ versus 10%; CI, 2-19% for ERM-), although the effect of ERM was not statistically significant (P = 0.15 in multiple regression analysis). Our results indicate that ERM at diagnosis may be a favorable prognostic factor for OS in adult AML.
authors.affiliation: The Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: K J
authors.initials: KJ
authors.lastname: Kopecky
authors.forename: A
authors.initials: A
authors.lastname: Mohan
authors.forename: C L
authors.initials: CL
authors.lastname: Willman
authors.forename: F R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: J K
authors.initials: JK
authors.lastname: Weick
authors.forename: J P
authors.initials: JP
authors.lastname: Issa
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000737:chemistry; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000737:chemistry*; D003630:Daunorubicin / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000145:classification / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009360:Neoplastic Cells, Circulating; D014411:Neoplastic Stem Cells / Q000737:chemistry*; D011379:Prognosis; D011960:Receptors, Estrogen / Q000235:genetics*; D012044:Regression Analysis
chemical_list: D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D003561:Cytarabine; D003630:Daunorubicin