METHYLATION of PIS and P16 GENES in ADULT ACUTE LEUKEMIA

Abstract

We investigated the frequency and prognostic significance of plS and p!6 gene methylation in adult acute leukemia. The methylation specific polymerase chain reaction (MS-PCR) was used to analyze plS and pl6 gene methylation in 49 cases of acute lymphoblastic leukemia (ALL) and 29 cases of acute myelogenous leukemia (AML). At presentation, 93 % of cases in AML (8/8 Ml, 10/11 M2, 2/2 M4, 5/6 M5 and 2/2 M6) showedp/5 methylation, but none showedp!6 methylation. In ALL, 57% (5/8 T-ALL, 14/ 26 common-ALL, 4/5 pre-B ALL, 1/3 early B precursor ALL and 4/7 mixed lineage ALL) showed pi5 methylation. Only 6% showed pI6 methylation, all of whom had concomitant pi5 methylation. One patient acquired p!6 methylation during relapse. For 23 ALL cases karyotyped,/>/5 methylation was found in 6/9 cases with normal karyotype, 3/7 cases with the Philadelphia chromosome, 3/3 cases with 9p-, 2/2 cases with complex karyotypes and 1/1 case with hyperdiploidy. Three more cases with unsuccessful karyotyping but BCR' ABL fusion showed plS methylation as well. Five ALL patients were tested serially for minimal residual disease (MRD) with MS-PCR that has a sensitivity of ICH to 10J. All showed continuous positive MS-PCR that heralded hématologie relapse. The prognostic significance of pi 5 methylation was tested in ALL patients, showing no impact on complete; remission rate, 5-year overall survival and 5-year disease free survival.