Microsatellite instability is not an uncommon finding in adult de novo acute myeloid leukemia

Autor: Granada Perea, Anna Aventin, Salut Brunet, Adriana Lasa, Maria J. Carnicer, Jorge Sierra, Josep F. Nomdedeu, Camino Estivill
Rok vydání: 2005
Předmět:
Male
DNA Repair
Bone Marrow
Antineoplastic Combined Chemotherapy Protocols
Life Tables
Gene Expression Regulation
Leukemic
Remission Induction
Hematopoietic Stem Cell Transplantation
Nuclear Proteins
Myeloid leukemia
DNA
Neoplasm
Hematology
General Medicine
Middle Aged
Prognosis
Combined Modality Therapy
Neoplasm Proteins
DNA-Binding Proteins
Leukemia
MutS Homolog 2 Protein
Real-time polymerase chain reaction
Leukemia
Myeloid
Acute Disease
Microsatellite
Female
MutL Protein Homolog 1
Adult
Risk
congenital
hereditary
and neonatal diseases and abnormalities
Adolescent
Biology
MLH1
Transplantation
Autologous
medicine
Humans
neoplasms
Adaptor Proteins
Signal Transducing
Chromosome Aberrations
nutritional and metabolic diseases
Microsatellite instability
Oncogenes
medicine.disease
Survival Analysis
Molecular biology
digestive system diseases
MSH6
MSH3
Karyotyping
Carrier Proteins
Microsatellite Repeats
Zdroj: Annals of Hematology. 84:368-375
ISSN: 1432-0584
0939-5555
Popis: 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.
Databáze: OpenAIRE
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