PURPOSE: To examine cancer genes undergoing epigenetic inactivation in a set of T-cell acute lymphoblastic leukemias (T-ALLs) to obtain the CpG island methylator phenotype (CIMP) in the disease and its possible correlation with clinical features and outcome of the patients. PATIENTS AND METHODS: Methylation-specific polymerase chain reaction was used to analyze methylation of the ADAMTS-1, ADAMTS-5, APAF-1, ASPP-1, CDH1, CDH13, DAPK, DIABLO, DKK-3, LATS-1, LATS-2, NES-1, p14, p15, p16, p57, p73, PARK-2, PTEN, sFRP1/2/4/5, SHP-1, SYK, TMS-1, and WIF-1 genes in samples from 50 consecutive T-ALL patients (19 children and 31 adults). Results were compared with results obtained in 286 B-cell acute lymphoblastic leukemias (B-ALLs). RESULTS: A total of 88% of the T-ALL samples had at least one gene methylated. According to the number of methylated genes observed in each individual sample, 12 patients (24%) were included in the CIMP- group (zero to two methylated genes), and 38 patients (76%) were included in the CIMP+ group (> two methylated genes). Clinical features and remission rate did not differ significantly among both groups of patients. Estimated disease-free survival (DFS) rate at 12 years and overall survival (OS) rate at 13 years were 100% and 91% for the CIMP- group and 20% and 17% for the CIMP+ group, respectively (P = .0006 and P = .003, respectively). Multivariate analysis demonstrated that methylation profile was an independent prognostic factor in predicting DFS (P = .05) and OS (P = .02). A group of five genes (SYK-1, ASPP-1, sFRP-2, sFRP-5, and WIF-1) showed specificity for T-ALL compared with B-ALL. CONCLUSION: Our results suggest that the methylation profile may be a potential new biomarker of risk prediction in T-ALL.
PURPOSE: To examine cancer genes undergoing epigenetic inactivation in a set of T-cell acute lymphoblastic leukemias (T-ALLs) to obtain the CpG island methylator phenotype (CIMP) in the disease and its possible correlation with clinical features and outcome of the patients. PATIENTS AND METHODS: Methylation-specific polymerase chain reaction was used to analyze methylation of the ADAMTS-1, ADAMTS-5, APAF-1, ASPP-1, CDH1, CDH13, DAPK, DIABLO, DKK-3, LATS-1, LATS-2, NES-1, p14, p15, p16, p57, p73, PARK-2, PTEN, sFRP1/2/4/5, SHP-1, SYK, TMS-1, and WIF-1 genes in samples from 50 consecutive T-ALL patients (19 children and 31 adults). Results were compared with results obtained in 286 B-cell acute lymphoblastic leukemias (B-ALLs). RESULTS: A total of 88% of the T-ALL samples had at least one gene methylated. According to the number of methylated genes observed in each individual sample, 12 patients (24%) were included in the CIMP- group (zero to two methylated genes), and 38 patients (76%) were included in the CIMP+ group (> two methylated genes). Clinical features and remission rate did not differ significantly among both groups of patients. Estimated disease-free survival (DFS) rate at 12 years and overall survival (OS) rate at 13 years were 100% and 91% for the CIMP- group and 20% and 17% for the CIMP+ group, respectively (P = .0006 and P = .003, respectively). Multivariate analysis demonstrated that methylation profile was an independent prognostic factor in predicting DFS (P = .05) and OS (P = .02). A group of five genes (SYK-1, ASPP-1, sFRP-2, sFRP-5, and WIF-1) showed specificity for T-ALL compared with B-ALL. CONCLUSION: Our results suggest that the methylation profile may be a potential new biomarker of risk prediction in T-ALL.
Authors: S C Mack; H Witt; R M Piro; L Gu; S Zuyderduyn; A M Stütz; X Wang; M Gallo; L Garzia; K Zayne; X Zhang; V Ramaswamy; N Jäger; D T W Jones; M Sill; T J Pugh; M Ryzhova; K M Wani; D J H Shih; R Head; M Remke; S D Bailey; T Zichner; C C Faria; M Barszczyk; S Stark; H Seker-Cin; S Hutter; P Johann; S Bender; V Hovestadt; T Tzaridis; A M Dubuc; P A Northcott; J Peacock; K C Bertrand; S Agnihotri; F M G Cavalli; I Clarke; K Nethery-Brokx; C L Creasy; S K Verma; J Koster; X Wu; Y Yao; T Milde; P Sin-Chan; J Zuccaro; L Lau; S Pereira; P Castelo-Branco; M Hirst; M A Marra; S S Roberts; D Fults; L Massimi; Y J Cho; T Van Meter; W Grajkowska; B Lach; A E Kulozik; A von Deimling; O Witt; S W Scherer; X Fan; K M Muraszko; M Kool; S L Pomeroy; N Gupta; J Phillips; A Huang; U Tabori; C Hawkins; D Malkin; P N Kongkham; W A Weiss; N Jabado; J T Rutka; E Bouffet; J O Korbel; M Lupien; K D Aldape; G D Bader; R Eils; P Lichter; P B Dirks; S M Pfister; A Korshunov; M D Taylor Journal: Nature Date: 2014-02-19 Impact factor: 49.962