Prognostic implications of mono-hit and multi-hit TP53 alterations in patients with acute myeloid leukemia and higher risk myelodysplastic syndromes treated with azacitidine-based therapy

Article Hematology

Molecular characterization of mutant TP53 acute myeloid leukemia and high-risk myelodysplastic syndrome

Tim Grob et al.

Summary: Mutant TP53 AML and MDS-EB share similar molecular characteristics and survival outcomes, suggesting that they should be considered as distinct molecular disease entities.

BLOOD (2022)

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Article Oncology

Myelodysplastic Syndromes, Version 3.2022 Featured Updates to the NCCN Guidelines

Peter L. Greenberg et al.

Summary: The NCCN Guidelines for Myelodysplastic Syndromes (MDS) provide recommendations for the evaluation, diagnosis, and management of patients with MDS based on clinical evidence. The 2022 updates include treatment recommendations for both lower-risk and higher-risk MDS, emerging therapies, supportive care recommendations, and genetic assessment for hereditary myeloid malignancy predisposition syndromes.

JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK (2022)

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Article Hematology

A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for higher-risk myelodysplastic syndromes

Amer M. Zeidan et al.

Summary: This study conducted a randomized phase 2 trial comparing the efficacy of Azacitidine plus Durvalumab with Azacitidine monotherapy in the treatment of higher-risk myelodysplastic syndromes. The results showed that the combination therapy did not significantly improve clinical outcomes and was associated with more toxicities.

BLOOD ADVANCES (2022)

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Article Hematology

A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for older patients with AML

Amer M. Zeidan et al.

Summary: Evidence suggests that combining immunotherapy with hypomethylating agents may enhance antitumor activity. However, in this study, the combination of durvalumab and azacitidine did not improve clinical efficacy compared with azacitidine alone in older patients with acute myeloid leukemia.

BLOOD ADVANCES (2022)

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Article Hematology

TP53 mutation defines a unique subgroup within complex karyotype de novo and therapy-related MDS/AML

Olga K. Weinberg et al.

Summary: This study evaluated the clinicopathologic features and outcomes of AML and MDS patients with complex karyotype (CK). The presence of TP53 mutation, especially multihit TP53 mutation, in the context of CK, identified a homogeneously aggressive disease, irrespective of blast count or therapy-relatedness.

BLOOD ADVANCES (2022)

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Article Hematology

TP53 copy number and protein expression inform mutation status across risk categories in acute myeloid leukemia

Mehrnoosh Tashakori et al.

Summary: Mutant TP53 is a risk factor in AML, but there is limited analysis of TP53 alterations in AML patients. Our study analyzed TP53 mutational status, copy number, and protein expression in AML patients and identified different hotspots and novel pathogenic variants involving TP53 splice sites. We found TP53 CN loss in TP53-mutated AML cases and copy neutral loss of heterozygosity in AML patients with intact TP53 CN. We also demonstrated that mutant p53 protein expression patterns can provide a readout that integrates TP53 mutation and allelic states in AML patients, regardless of TP53 CN status. Additionally, genomic analysis of comutations in TP53-mutant AML showed mutations in genes involved in epigenetic regulation, RAS/MAPK signaling, and RNA splicing. This study provides insights for risk stratification of AML patients based on integrated molecular and protein-level TP53 analyses.

BLOOD (2022)

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Review Oncology

Are We Moving the Needle for Patients with TP53-Mutated Acute Myeloid Leukemia?

Rory M. Shallis et al.

Summary: TP53-mutated AML is a high-risk form of AML, and the currently available treatment options are insufficient. Clinical trials should be recommended for newly diagnosed patients. Novel agents, such as CD47/SIRP alpha axis and TIM-3 inhibitors, show promise in treating this disease. However, there is no standard of care due to the lack of clear differences in treatment outcomes.

CANCERS (2022)

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Article Hematology

Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN

Hartmut Doehner et al.

Summary: The 2010 and 2017 editions of the European LeukemiaNet recommendations for AML diagnosis and management are widely recognized. There have been major advances in our understanding of AML, including disease classification updates, improvements in genomic diagnostics, and the development of new therapeutic agents. This update includes a revised genetic risk classification, response criteria, and treatment recommendations.

BLOOD (2022)

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Article Hematology

International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data

Daniel A. Arber et al.

Summary: In 2016, the WHO, Society for Hematopathology, and European Association for Haematopathology collaborated to update the classification of myeloid neoplasms and acute leukemias, advancing the field of myeloid neoplasms and acute leukemias.

BLOOD (2022)

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Review Oncology

The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms

Joseph D. Khoury et al.

Summary: This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms, emphasizing the refinement of diagnostic criteria and the importance of actionable biomarkers, while maintaining global applicability.

LEUKEMIA (2022)

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Article Biochemistry & Molecular Biology