title: Microsatellite instability is not an uncommon finding in adult de novo acute myeloid leukemia.
abstract: To investigate the biologic relevance of microsatellite instability (MSI) in de novo acute myeloid leukemia (AML), 102 consecutive adult patients were analyzed by using a panel of seven microsatellites (BAT25, BAT26, D13S1267, D13S174, D2S123, D5S346 and Mdf15). Frame-shift mutations in the repetitive sequences in the coding region of MSH3, MSH6, BAX, TGFBRII and IGFRII were also investigated by using a fluorescent PCR-based assay. Methylation-specific PCR was used to determine the methylation status of hMLH1 in MSI+ cases. MSH3, MSH6 and MLH1 expression was also analyzed in 68 cases by means of real-time quantitative PCR. MSI was detected in 20 cases: 14 cases had MSI-high (instability of at least two microsatellite markers) and 6 cases corresponded to MSI-low (a single polymorphic marker with instability). Six MSI+ cases showed an associated MLL rearrangement (p=0.002). No single case showed a mutation in the repetitive sequences of the MSH3, MSH6, BAX, TGFBRII and IGFRII genes. Most samples displayed low mRNA levels of the repair genes. hMLH1 promoter was hypermethylated in five MSI+ cases. Overall survival analysis revealed no adverse effect of MSI positivity. These results suggest that MSI may be a common biologic finding in de novo AML.
authors.affiliation: Department of Hematology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. jnomdedeu@hsp.santpau.es
authors.forename: Josep F
authors.initials: JF
authors.lastname: Nomdedéu
authors.forename: Granada
authors.initials: G
authors.lastname: Perea
authors.forename: Camino
authors.initials: C
authors.lastname: Estivill
authors.forename: Adriana
authors.initials: A
authors.lastname: Lasa
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Carnicer
authors.forename: Salut
authors.initials: S
authors.lastname: Brunet
authors.forename: Anna
authors.initials: A
authors.lastname: Aventín
authors.forename: Jorge
authors.initials: J
authors.lastname: Sierra
mesh_terms: D000208:Acute Disease; D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D002869:Chromosome Aberrations; D003131:Combined Modality Therapy; D004260:DNA Repair / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D015993:Life Tables; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D009857:Oncogenes; D011379:Prognosis; D012074:Remission Induction; D012306:Risk; D016019:Survival Analysis; D014182:Transplantation, Autologous
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein