Comparison of acute myeloid leukemia and myelodysplastic syndromes with TP53 aberrations

Dutta, Sayantanee; Moritz, Jennifer; Pregartner, Gudrun; Thallinger, Gerhard; Brandstätter, Ilona; Lind, Karin; Rezania, Simin; Lyssy, Freya; Reinisch, Andreas; Zebisch, Armin; Berghold, Andrea; Wölfler, Albert; Sill, Heinz

doi:10.1007/s00277-022-04766-2

Cited by 10 publications

(7 citation statements)

References 46 publications

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“…The bone marrow blast cut‐off point of 20% that separates MDS from AML among myeloid malignancies is still up for dispute 21 . Given their distinct clinical characteristics and dismal prognosis, a growing body of evidence demonstrates that MDS and AML with TP53 mutations may comprise a unique continuum of myeloid malignancies 22–24 . It seems arbitrary to use the diagnostic cut‐off of bone marrow blasts percentage to distinguish between MDS and AML and it is unable to represent the biological continuity that myeloid pathogenic processes naturally possess 25 .…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization and prognosis of mutant TP53 acute myeloid leukemia and myelodysplastic syndrome with excess blasts

Shen

Zhang

et al. 2023

Int J Lab Hematology

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Introduction Myeloid tumors typically harbor TP53 mutations, which are linked to a dismal prognosis. There are fewer studies on whether TP53‐mutated acute myeloid leukemia (AML) and myelodysplastic syndrome with excess blasts (MDS‐EB) differ in molecular characteristics and should be considered as separate entities. Methods Between January 2016 and December 2021, a retrospective analysis was done on a total of 73 newly diagnosed AML patients and 61 MDS‐EB patients from the first affiliated hospital of Soochow University. We described a survival profile and a thorough characterization of newly found TP53‐mutant AML and MDS‐EB and investigated the relationship between these characteristics and overall survival (OS). Results 38 (31.1%) were mono‐allelic, and 84 (68.9%) were bi‐allelic. There is no significant difference between TP53‐mutated AML and MDS‐EB (median OS 12.9 verse 14.4 months; p = .558). Better overall survival was linked to mono‐allelic TP53 than bi‐allelic TP53(HR = 3.030, CI:1.714–5.354, p < .001). However, the number of TP53 mutations and comutations were not significantly associated with OS. TP53 variant allele frequency cutoff of 50% is significant correlation with OS (HR: 2.177, 95% CI: 1.142–4.148; p = .0063). Conclusion Our data revealed that allele status and allogeneic hematopoietic stem cell transplant independently affect the prognostic of AML and MDS‐EB patients, with a concordance of molecular features and survival between these two disease entities. Our analysis favors considering TP53‐mutated AML/MDS‐EB as a distinct disorder.

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Section: Discussionmentioning

confidence: 99%

Molecular characterization and prognosis of mutant TP53 acute myeloid leukemia and myelodysplastic syndrome with excess blasts

Shen

Zhang

et al. 2023

Int J Lab Hematology

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“…As boundaries between AML and MDS fade in current classifications [ 38 ], recent data indicate that TP53 -mutated AML and MDS with excess blasts share similar characteristics and prognoses, suggesting they should be regarded as a specific molecular disease entity [ 112 , 113 , 114 ].…”

Section: Genetic Risk Profilementioning

confidence: 99%

Modern Risk Stratification of Acute Myeloid Leukemia in 2023: Integrating Established and Emerging Prognostic Factors

Boscaro¹,

Urbino²,

Catania³

et al. 2023

Cancers

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An accurate estimation of AML prognosis is complex since it depends on patient-related factors, AML manifestations at diagnosis, and disease genetics. Furthermore, the depth of response, evaluated using the level of MRD, has been established as a strong prognostic factor in several AML subgroups. In recent years, this rapidly evolving field has made the prognostic evaluation of AML more challenging. Traditional prognostic factors, established in cohorts of patients treated with standard intensive chemotherapy, are becoming less accurate as new effective therapies are emerging. The widespread availability of next-generation sequencing platforms has improved our knowledge of AML biology and, consequently, the recent ELN 2022 recommendations significantly expanded the role of new gene mutations. However, the impact of rare co-mutational patterns remains to be fully disclosed, and large international consortia such as the HARMONY project will hopefully be instrumental to this aim. Moreover, accumulating evidence suggests that clonal architecture plays a significant prognostic role. The integration of clinical, cytogenetic, and molecular factors is essential, but hierarchical methods are reaching their limit. Thus, innovative approaches are being extensively explored, including those based on “knowledge banks”. Indeed, more robust prognostic estimations can be obtained by matching each patient’s genomic and clinical data with the ones derived from very large cohorts, but further improvements are needed.

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“… 105 These similarities between TP53 aberrant MDS and AML were confirmed by Dunn et al through the analysis of 84 patients with TP53 -mutated AML and MDS patients. 170 …”

Section: Tp53-mutated Mds and Amlmentioning

confidence: 99%

Tp53-Mutated Myelodysplasia and Acute Myeloid Leukemia

Testa¹,

Castelli

Pelosi

2023

Mediterr J Hematol Infect Dis

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TP53-mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) form a distinct and heterogeneous group of myeloid malignancies associated with poor outcomes. Studies carried out in the last years have in part elucidated the complex role played by TP53 mutations in the pathogenesis of these myeloid disorders and in the mechanisms of drug resistance. A consistent number of studies has shown that some molecular parameters, such as the presence of a single or multiple TP53 mutations, the presence of concomitant TP53 deletions, the association with co-occurring mutations, the clonal size of TP53 mutations, the involvement of a single (monoallelic) or of both TP53 alleles (biallelic) and the cytogenetic architecture of concomitant chromosome abnormalities are major determinants of outcomes of patients. The limited response of these patients to standard treatments, including induction chemotherapy, hypomethylating agents, and venetoclax-based therapies and the discovery of an immune dysregulation have induced a shift to new emerging therapies, some of which being associated with promising efficacy. The main aim of these novel immune and nonimmune strategies consists in improving survival and in increasing the number of TP53-mutated MDS/AML patients in remission amenable to allogeneic stem cell transplantation. Keywords: myelodysplastic syndromes; acute myeloid leukemias; TP53; molecular abnormalities; gene sequencing; cytogenetic characterization

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Comparison of acute myeloid leukemia and myelodysplastic syndromes with TP53 aberrations

Cited by 10 publications

References 46 publications

Molecular characterization and prognosis of mutant TP53 acute myeloid leukemia and myelodysplastic syndrome with excess blasts

Molecular characterization and prognosis of mutant TP53 acute myeloid leukemia and myelodysplastic syndrome with excess blasts

Modern Risk Stratification of Acute Myeloid Leukemia in 2023: Integrating Established and Emerging Prognostic Factors

Tp53-Mutated Myelodysplasia and Acute Myeloid Leukemia

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