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Cancers
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TP53 in Solid Tumors and Hematological Malignancies
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TP53 in Solid Tumors and Hematological Malignancies

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 8810

Special Issue Editor

Dr. Cristina Papayannidis

E-Mail Website
Guest Editor
Istituto di Ematologia “Seràgnoli”, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
Interests: acute myeloid leukemia; bone marrow; cytarabine; cell cycle proteins; mitoxantrone

Special Issue Information

Somatic mutations in the TP53 gene are one of the most frequent alterations in human cancers, mostly consisting of single-base substitutions distributed throughout the coding sequence, and are considered potential prognostic and predictive markers, as well as targets for pharmacological intervention.

In solid tumors and hematological malignancies, the frequency of TP53 mutations is relatively low compared to other tumors. Nevertheless, incidence increases in some cases with disease progression and is associated with a poor prognosis. Several therapeutic approaches have been tested or are currently in clinical development, aiming to target the TP53 pathway, either by blocking its interaction with MDM2 or by restoring the function of the altered protein. However, in TP53 mutated cases, an effective therapeutic option is still lacking.

This Special Issue will be focused on mechanisms of deregulation of TP53 and consequent prognostic impact in solid tumors and hematological malignancies, including acute and chronic leukemias, multiple myeloma, myelodisplastic syndromes and lymphomas, as well as the therapeutic options to interact with the TP53 pathway, highlighting future perspectives for improving treatment and cure rates in such aggressive diseases.

Dr. Cristina Papayannidis
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • TP53
  • myelodisplastic syndromes
  • lymphoma
  • leukemia
  • multiple myeloma
  • target therapy
  • MDM2

Published Papers (3 papers)

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Research

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13 pages, 929 KiB  
Article
Influence of TP53 Mutation on Survival of Diffuse Large B-Cell Lymphoma in the CAR T-Cell Era
by Edit Porpaczy, Philipp Wohlfarth, Oliver Königsbrügge, Werner Rabitsch, Cathrin Skrabs, Philipp Staber, Nina Worel, Leonhard Müllauer, Ingrid Simonitsch-Klupp, Christoph Kornauth, Johannes Rohrbeck, Ulrich Jaeger and Ana-Iris Schiefer
Cancers 2021, 13(22), 5592; https://doi.org/10.3390/cancers13225592 - 09 Nov 2021
Cited by 9 | Viewed by 2933
Abstract
Refractory/relapsed diffuse large B-cell lymphoma (DLBCL) is associated with poor outcome. The clinical behavior and genetic landscape of DLBCL is heterogeneous and still not fully understood. TP53 mutations in DLBCL have been identified as markers of poor prognosis and are often associated with [...] Read more.
Refractory/relapsed diffuse large B-cell lymphoma (DLBCL) is associated with poor outcome. The clinical behavior and genetic landscape of DLBCL is heterogeneous and still not fully understood. TP53 mutations in DLBCL have been identified as markers of poor prognosis and are often associated with therapeutic resistance. Chimeric antigen receptor T-cell therapy is an innovative therapeutic concept and represents a game-changing therapeutic option by supporting the patient’s own immune system to kill the tumor cells. We investigated the impact of TP53 mutations on the overall survival of refractory/relapsed DLBCL patients treated with comparable numbers of therapy lines. The minimum number of therapy lines was 2 (median 4), including either anti-CD19 CAR T-cell therapy or conventional salvage therapy. A total of 170 patients with DLBCL and high-grade B-cell lymphoma with MYC, BCL2, and/or BCL6 rearrangements (DHL/THL), diagnosed and treated in our hospital between 2000 and 2021, were included. Twenty-nine of them received CAR T-cell therapy. TP53 mutations were found in 10/29 (35%) and 31/141 (22%) of patients in the CAR T-cell and conventional groups, respectively. Among the 141 patients not treated with CAR T cells, TP53 mutation was an independent prognostic factor for overall survival (OS) (median 12 months with TP53 vs. not reached without TP53 mutation, p < 0.005), but in the CAR T cell treated group, this significance could not be shown (median OS 30 vs. 120 months, p = 0.263). The findings from this monocentric retrospective study indicate that TP53 mutation status does not seem to affect outcomes in DLBCL patients treated with CAR T-cell therapy. Detailed evaluation in large cohorts is warranted. Full article
(This article belongs to the Special Issue TP53 in Solid Tumors and Hematological Malignancies)
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14 pages, 833 KiB  
Article
TP53 Combined Phenotype Score Is Associated with the Clinical Outcome of TP53-Mutated Myelodysplastic Syndromes
by Mariko Yabe, Aidana Z. Omarbekova, Meier Hsu, Hannah May, Maria E. Arcila, Ying Liu, Ahmet Dogan, Andrew M. Brunner, Valentina Nardi, Robert P. Hasserjian and Virginia M. Klimek
Cancers 2021, 13(21), 5502; https://doi.org/10.3390/cancers13215502 - 02 Nov 2021
Cited by 2 | Viewed by 2089
Abstract
Mutations of TP53 are observed in 5–10% of patients in myelodysplastic syndrome (MDS) and are associated with adverse outcomes. Previous studies indicate that the TP53 allelic state and variant allele frequency of TP53 mutation impact patient outcomes, but there is significant heterogeneity within [...] Read more.
Mutations of TP53 are observed in 5–10% of patients in myelodysplastic syndrome (MDS) and are associated with adverse outcomes. Previous studies indicate that the TP53 allelic state and variant allele frequency of TP53 mutation impact patient outcomes, but there is significant heterogeneity within this MDS subgroup. We performed retrospective review of clinicopathologic and genomic information of 107 patients with TP53-mutated MDS. We assessed each mutation according to the phenotypic annotation of TP53 mutations (PHANTM) and analyzed the associations between predicted TP53 mutant function, represented by the PHANTM combined phenotype score, and overall survival (OS) using the log rank test and Cox regression. Our results indicated that patients with PHANTM combined phenotype score above the median (>1) had significantly shorter OS compared to those with scores below the median (median OS: 10.59 and 16.51 months, respectively, p = 0.025). This relationship remained significant in multivariable analysis (HR (95%CI): 1.62 (1.01–2.58), p = 0.044) and identified to have an independent prognostic influence, accounting for known risk such as IPSS-R and other standard risk variables. Our results suggest that the functional information of TP53 mutations, represented by PHANTM combined phenotype score, are associated with the clinical outcome of patients with TP53-mutated MDS. Full article
(This article belongs to the Special Issue TP53 in Solid Tumors and Hematological Malignancies)
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Review

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22 pages, 1514 KiB  
Review
TP53 in Myelodysplastic Syndromes
by Yan Jiang, Su-Jun Gao, Benoit Soubise, Nathalie Douet-Guilbert, Zi-Ling Liu and Marie-Bérengère Troadec
Cancers 2021, 13(21), 5392; https://doi.org/10.3390/cancers13215392 - 27 Oct 2021
Cited by 10 | Viewed by 3072
Abstract
Myelodysplastic syndromes (MDSs) are heterogeneous for their morphology, clinical characteristics, survival of patients, and evolution to acute myeloid leukemia. Different prognostic scoring systems including the International Prognostic Scoring System (IPSS), the Revised IPSS, the WHO Typed Prognostic Scoring System, and the Lower-Risk Prognostic [...] Read more.
Myelodysplastic syndromes (MDSs) are heterogeneous for their morphology, clinical characteristics, survival of patients, and evolution to acute myeloid leukemia. Different prognostic scoring systems including the International Prognostic Scoring System (IPSS), the Revised IPSS, the WHO Typed Prognostic Scoring System, and the Lower-Risk Prognostic Scoring System have been introduced for categorizing the highly variable clinical outcomes. However, not considered by current MDS prognosis classification systems, gene variants have been identified for their contribution to the clinical heterogeneity of the disease and their impact on the prognosis. Notably, TP53 mutation is independently associated with a higher risk category, resistance to conventional therapies, rapid transformation to leukemia, and a poor outcome. Herein, we discuss the features of monoallelic and biallelic TP53 mutations within MDS, their corresponding carcinogenic mechanisms, their predictive value in current standard treatments including hypomethylating agents, allogeneic hematopoietic stem cell transplantation, and lenalidomide, together with the latest progress in TP53-targeted therapy strategies, especially MDS clinical trial data. Full article
(This article belongs to the Special Issue TP53 in Solid Tumors and Hematological Malignancies)
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