Clinical outcomes and characteristics of patients with TP53-mutated acute myeloid leukemia or myelodysplastic syndromes: a single center experience*

References

• Bullinger L, Döhner K, Döhner H. Genomics of acute myeloid leukemia diagnosis and pathways. JCO. 2017;35(9):934–946.
   PubMed Web of Science ®Google Scholar
• Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374(23):2209–2221.
   PubMed Web of Science ®Google Scholar
• Dohner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424–447.
   PubMed Web of Science ®Google Scholar
• Papaemmanuil E, Gerstung M, Malcovati L, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013;122(22):3616–3627. quiz 99.
   PubMed Web of Science ®Google Scholar
• Bykov VJN, Eriksson SE, Bianchi J, et al. Targeting mutant p53 for efficient cancer therapy. Nat Rev Cancer. 2018;18(2):89–102.
   PubMed Web of Science ®Google Scholar
• Vousden KH, Prives C. Blinded by the light: the growing complexity of p53. Cell. 2009;137(3):413–431.
   PubMed Web of Science ®Google Scholar
• Prokocimer M, Molchadsky A, Rotter V. Dysfunctional diversity of p53 proteins in adult acute myeloid leukemia: projections on diagnostic workup and therapy. Blood. 2017;130(6):699–712.
   PubMed Web of Science ®Google Scholar
• Metzeler KH, Herold T, Rothenberg-Thurley M, et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood. 2016;128(5):686–698.
   PubMed Web of Science ®Google Scholar
• Stengel A, Kern W, Haferlach T, et al. The impact of TP53 mutations and TP53 deletions on survival varies between AML, ALL, MDS and CLL: an analysis of 3307 cases. Leukemia. 2017;31(3):705–711.
   PubMed Web of Science ®Google Scholar
• Kadia TM, Jain P, Ravandi F, et al. TP53 mutations in newly diagnosed acute myeloid leukemia: Clinicomolecular characteristics, response to therapy, and outcomes. Cancer. 2016;122(22):3484–3491.
   PubMed Web of Science ®Google Scholar
• Rucker FG, Schlenk RF, Bullinger L, et al. TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome. Blood. 2012;119(9):2114–2121.
   PubMed Web of Science ®Google Scholar
• Wong TN, Ramsingh G, Young AL, et al. Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia. Nature. 2015;518(7540):552–555.
   PubMed Web of Science ®Google Scholar
• Haase D, for the International Working Group for MDS Molecular Prognostic Committee, Stevenson KE, Neuberg D, et al. TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups. Leukemia. 2019;33(7):1747–1758.
   PubMed Web of Science ®Google Scholar
• Mrózek K, Eisfeld A-K, Kohlschmidt J, et al. Complex karyotype in de novo acute myeloid leukemia: typical and atypical subtypes differ molecularly and clinically. Leukemia. 2019;33(7):1620–1634.
   PubMed Web of Science ®Google Scholar
• Bewersdorf JP, Ardasheva A, Podoltsev NA, et al. From clonal hematopoiesis to myeloid leukemia and what happens in between: will improved understanding lead to new therapeutic and preventive opportunities?. Blood Rev. 2019; 37:100587.
   PubMed Web of Science ®Google Scholar
• Zeidan AM, Al Ali N, Barnard J, et al. Comparison of clinical outcomes and prognostic utility of risk stratification tools in patients with therapy-related vs de novo myelodysplastic syndromes: a report on behalf of the MDS Clinical Research Consortium. Leukemia. 2017;31(6):1391–1397.
   PubMed Web of Science ®Google Scholar
• Abou Zahr A, Kavi AM, Mukherjee S, et al. Therapy-related myelodysplastic syndromes, or are they? Blood Rev. 2017;31(3):119–128.
   PubMed Web of Science ®Google Scholar
• Leung GMK, Zhang C, Ng NKL, et al. Distinct mutation spectrum, clinical outcome and therapeutic responses of typical complex/monosomy karyotype acute myeloid leukemia carrying TP53 mutations. Am J Hematol. 2019;94(6):650–657.
   PubMed Web of Science ®Google Scholar
• Cheson BD, Greenberg PL, Bennett JM, et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006;108(2):419–425.
   PubMed Web of Science ®Google Scholar
• Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. JCO. 2003;21(24):4642–4649.
   PubMed Web of Science ®Google Scholar
• Ok CY, Patel KP, Garcia-Manero G, et al. Mutational profiling of therapy-related myelodysplastic syndromes and acute myeloid leukemia by next generation sequencing, a comparison with de novo diseases. Leuk Res. 2015;39(3):348–354.
   PubMed Web of Science ®Google Scholar
• Pedersen-Bjergaard J, Andersen MK, Andersen MT, et al. Genetics of therapy-related myelodysplasia and acute myeloid leukemia. Leukemia. 2008;22(2):240–248.
   PubMed Web of Science ®Google Scholar
• Welch JS. Patterns of mutations in TP53 mutated AML. Best Pract Res Clin Haematol. 2018;31(4):379–383.
   PubMed Web of Science ®Google Scholar
• Sabapathy K, Lane DP. Therapeutic targeting of p53: all mutants are equal, but some mutants are more equal than others. Nat Rev Clin Oncol. 2018;15(1):13–30.
   PubMed Web of Science ®Google Scholar
• Bernard E, Nannya Y, Yoshizato T, et al. TP53 state dictates genome stability, clinical presentation and outcomes in myelodysplastic syndromes. Blood. 2019;134(Supplement_1):675–675.
   Web of Science ®Google Scholar
• Giacomelli AO, Yang X, Lintner RE, et al. Mutational processes shape the landscape of TP53 mutations in human cancer. Nat Genet. 2018;50(10):1381–1387.
   PubMed Web of Science ®Google Scholar
• Boettcher S, Miller PG, Sharma R, et al. A dominant-negative effect drives selection of TP53 missense mutations in myeloid malignancies. Science. 2019;365(6453):599–604.
   PubMed Web of Science ®Google Scholar
• Lehmann S, Bykov VJ, Ali D, et al. Targeting p53 in vivo: a first-in-human study with p53-targeting compound APR-246 in refractory hematologic malignancies and prostate cancer. JCO. 2012;30(29):3633–3639.
   PubMed Web of Science ®Google Scholar
• Sallman DA, DeZern AE, Steensma DP, et al. Phase 1b/2 combination study of APR-246 and Azacitidine (AZA) in patients with TP53 mutant myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Blood. 2018;132(Supplement 1):3091–3091.
   Google Scholar
• Prochazka KT, Pregartner G, Rücker FG, et al. Clinical implications of subclonal TP53 mutations in acute myeloid leukemia. Haematologica. 2019;104(3):516–523.
   PubMed Web of Science ®Google Scholar
• Sallman DA, Komrokji R, Vaupel C, et al. Impact of TP53 mutation variant allele frequency on phenotype and outcomes in myelodysplastic syndromes. Leukemia. 2016;30(3):666–673.
   PubMed Web of Science ®Google Scholar
• Belickova M, Vesela J, Jonasova A, et al. TP53 mutation variant allele frequency is a potential predictor for clinical outcome of patients with lower-risk myelodysplastic syndromes. Oncotarget. 2016;7(24):36266–36279.
   PubMedGoogle Scholar
• Bejar R, Papaemmanuil E, Haferlach T, et al. Somatic mutations in MDS patients are associated with clinical features and predict prognosis independent of the IPSS-R: analysis of combined datasets from the International Working Group for Prognosis in MDS-Molecular Committee. Blood. 2015;126(23):907–907.
   Web of Science ®Google Scholar
• Welch JS, Petti AA, Miller CA, et al. TP53 and decitabine in acute myeloid leukemia and myelodysplastic syndromes. N Engl J Med. 2016;375(21):2023–2036.
   PubMed Web of Science ®Google Scholar
• Roboz GJ, Mandrekar SJ, Desai P, et al. Randomized trial of 10 days of decitabine ± bortezomib in untreated older patients with AML: CALGB 11002 (Alliance). Blood Advances. 2018;2(24):3608–3617.
   PubMed Web of Science ®Google Scholar
• Short NJ, Kantarjian HM, Loghavi S, et al. Treatment with a 5-day versus a 10-day schedule of decitabine in older patients with newly diagnosed acute myeloid leukaemia: a randomised phase 2 trial. Lancet Haematol. 2019;6(1):e29–e37.
   PubMed Web of Science ®Google Scholar
• Aldoss I, Pham A, Li SM, et al. Favorable impact of allogeneic stem cell transplantation in patients with therapy-related myelodysplasia regardless of TP53 mutational status. Haematologica. 2017;102(12):2030–2038.
   PubMed Web of Science ®Google Scholar
• Bejar R, Stevenson KE, Caughey B, et al. Somatic mutations predict poor outcome in patients with myelodysplastic syndrome after hematopoietic stem-cell transplantation. JCO. 2014;32(25):2691–2698.
   PubMed Web of Science ®Google Scholar
• Lindsley RC, Saber W, Mar BG, et al. Prognostic mutations in myelodysplastic syndrome after stem-cell transplantation. N Engl J Med. 2017;376(6):536–547.
   PubMed Web of Science ®Google Scholar
• Ciurea SO, Chilkulwar A, Saliba RM, et al. Prognostic factors influencing survival after allogeneic transplantation for AML/MDS patients with TP53 mutations. Blood. 2018;131(26):2989–2992.
   PubMed Web of Science ®Google Scholar
• Middeke JM, Fang M, Cornelissen JJ, Mohr B, et al. Outcome of patients with abnl(17p) acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. Blood. 2014;123(19):2960–2967.
   PubMed Web of Science ®Google Scholar
• Kharfan-Dabaja MA, Komrokji RS, Zhang Q, et al. TP53 and IDH2 somatic mutations are associated with inferior overall survival after allogeneic hematopoietic cell transplantation for myelodysplastic syndrome. Clin Lymphoma Myeloma Leuk. 2017;17(11):753–758.
   PubMed Web of Science ®Google Scholar
• Duncavage EJ, Jacoby MA, Chang GS, et al. Mutation clearance after transplantation for myelodysplastic syndrome. N Engl J Med. 2018;379(11):1028–1041.
   PubMed Web of Science ®Google Scholar
• Yoshizato T, Nannya Y, Atsuta Y, et al. Genetic abnormalities in myelodysplasia and secondary acute myeloid leukemia: impact on outcome of stem cell transplantation. Blood. 2017;129(17):2347–2358.
   PubMed Web of Science ®Google Scholar
• Poiré X, Labopin M, Maertens J, et al. Allogeneic stem cell transplantation in adult patients with acute myeloid leukaemia and 17p abnormalities in first complete remission: a study from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT). J Hematol Oncol. 2017;10(1):20.
   PubMed Web of Science ®Google Scholar
• Platzbecker U, Middeke JM, Sockel K, et al. Measurable residual disease-guided treatment with azacitidine to prevent haematological relapse in patients with myelodysplastic syndrome and acute myeloid leukaemia (RELAZA2): an open-label, multicentre, phase 2 trial. Lancet Oncol. 2018;19(12):1668–1679.
   PubMed Web of Science ®Google Scholar
• Thol F, Gabdoulline R, Liebich A, et al. Measurable residual disease monitoring by NGS before allogeneic hematopoietic cell transplantation in AML. Blood. 2018;132(16):1703–1713.
   PubMed Web of Science ®Google Scholar
• Bewersdorf JP, Shallis RM, Boddu PC, et al. The minimal that kills: Why defining and targeting measurable residual disease is the “Sine Qua Non” for further progress in management of acute myeloid leukemia. Blood Rev. 2019;100650. doi: 10.1016/j.blre.2019.100650
   PubMed Web of Science ®Google Scholar
• Wei AH, Döhner H, Pocock C, et al. The QUAZAR AML-001 maintenance trial: results of a Phase III international, randomized, double-blind, placebo-controlled study of CC-486 (Oral Formulation of Azacitidine) in patients with acute myeloid leukemia (AML) in first remission. Blood. 2019;134(Supplement_2):LBA-3–LBA.
   Web of Science ®Google Scholar
• Liu Y, Chen C, Xu Z, et al. Deletions linked to TP53 loss drive cancer through p53-independent mechanisms. Nature. 2016;531(7595):471–475.
   PubMed Web of Science ®Google Scholar