14 research outputs found
Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes
Tumor protein p53 (TP53) is the most frequently mutated gene in cancer1,2. In patients with myelodysplastic syndromes (MDS), TP53 mutations are associated with high-risk disease3,4, rapid transformation to acute myeloid leukemia (AML)5, resistance to conventional therapies6–8 and dismal outcomes9. Consistent with the tumor-suppressive role of TP53, patients harbor both mono- and biallelic mutations10. However, the biological and clinical implications of TP53 allelic state have not been fully investigated in MDS or any other cancer type. We analyzed 3,324 patients with MDS for TP53 mutations and allelic imbalances and delineated two subsets of patients with distinct phenotypes and outcomes. One-third of TP53-mutated patients had monoallelic mutations whereas two-thirds had multiple hits (multi-hit) consistent with biallelic targeting. Established associations with complex karyotype, few co-occurring mutations, high-risk presentation and poor outcomes were specific to multi-hit patients only. TP53 multi-hit state predicted risk of death and leukemic transformation independently of the Revised International Prognostic Scoring System (IPSS-R)11. Surprisingly, monoallelic patients did not differ from TP53 wild-type patients in outcomes and response to therapy. This study shows that consideration of TP53 allelic state is critical for diagnostic and prognostic precision in MDS as well as in future correlative studies of treatment response
PB1776: ABC TRANSPORTERS AFFECT THE SENSITIVITY OF ACUTE MYELOID LEUKEMIA BLASTS TO CHEMOTHERAPY
P729: DEREGULATION OF NONCODING RNAS DERIVED FROM KDM GENES IS ASSOCIATED WITH AZACITIDINE RESPONSE IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES AND ACUTE MYELOID LEUKEMIA
Favourable response to antithymocyte or antilymphocyte globulin in low-risk myelodysplastic syndrome patients with a ‘non-clonal’ pattern of X-chromosome inactivation in bone marrow cells
Investigation of DNA repair gene variants on myelodysplastic syndromes in a Turkish population
The aim of this study was to assess the possible influence of genetic polymorphisms in hOGG1, XRCC1, XRCC3, XPD, XPG and APE1 on the observed DNA damage in a group of Turkish myelodysplastic syndrome (MDS) patients. A total of 39 patients with myelodysplastic syndrome and 78 age-matched healthy control subjects were included in our study. Polymerase chain reaction/restriction fragment length polymorphism analysis was performed for the detection of DNA repair gene variants. No significant differences in DNA repair enzymes APE1, XRCC1 and XPG were found between MDS patients and controls. On the other hand, XRCC3, XPD and hOGG1 were associated with an increased risk of MDS (p = 0.004, p = 0.000, p = 0.017, respectively). Specifically, Thr/Met genotype was more relevant in patients (p = 0.026) in XRCC3; in hOGG1, Cys+ genotype was found higher in patients (p = 0.017); and in XPD, Gln/Gln genotypes were found higher in the patient (p = 0.001). In conclusion, XRCC3, XPD and hOGG1 genotypes are associated with an increased MDS risk, suggesting their possible involvement in the pathogenesis and biology of this disease