51 research outputs found
Characterization of oral and gut microbiome temporal variability in hospitalized cancer patients
Quantitative proteomic analysis of histone modifications in decitabine sensitive and resistant leukemia cell lines
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
Intensive chemotherapy is more effective than hypomethylating agents for the treatment of younger patients with myelodysplastic syndrome and elevated bone marrow blasts
P763: VENETOCLAX WITH AZACITIDINE IN RELAPSE/REFRACTORY HIGHER RISK MYELODYSPLASTIC SYNDROME: UPDATED PHASE 1 RESULTS
P754: INITIAL RESULTS OF PHASE I/II STUDY OF AZACITIDINE IN COMBINATION WITH QUIZARTINIB FOR PATIENTS WITH MYELODYSPLASTIC SYNDROME AND MYELODYSPLASTIC/MYELOPROLIFERATIVE NEOPLASM WITH FLT3 OR CBL MUTATION
P762: NONLINIEAR IMPACT OF CLINICAL FEATURES ON THE SURVIVAL OUTCOME OF MYELODYSPLASTIC SYNDROMES PATIENTS
S160: MOLECULAR DETERMINANTS OF DISEASE PROGRESSION AFTER HYPOMETHYLATING AGENT THERAPY IN RAS PATHWAY MUTANT CHRONIC MYELOMONOCYTIC LEUKEMIA AT THE SINGLE-CELL LEVEL
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