TP53-mutated acute myeloid leukemia and myelodysplastic syndrome : biology, treatment challenges, and upcoming approaches
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature..
Improved understanding of TP53 biology and the clinicopathological features of TP53-mutated myeloid neoplasms has led to the recognition of TP53-mutated acute myeloid leukemia/myelodysplastic syndrome (TP53m AML/MDS) as a unique entity, characterized by dismal outcomes following conventional therapies. Several clinical trials have investigated combinations of emerging therapies for these patients with the poorest molecular prognosis among myeloid neoplasms. Although some emerging therapies have shown improvement in overall response rates, this has not translated into better overall survival, hence the notion that p53 remains an elusive target. New therapeutic strategies, including novel targeted therapies, immune checkpoint inhibitors, and monoclonal antibodies, represent a shift away from cytotoxic and hypomethylating-based therapies, towards approaches combining non-immune and novel immune therapeutic strategies. The triple combination of azacitidine and venetoclax with either magrolimab or eprenetapopt have demonstrated safety in early trials, with phase III trials currently underway, and promising interim clinical results. This review compiles background on TP53 biology, available and emerging therapies along with their mechanisms of action for the TP53m disease entity, current treatment challenges, and recently published data and status of ongoing clinical trials for TP53m AML/MDS.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2024 |
---|---|
Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:103 |
---|---|
Enthalten in: |
Annals of hematology - 103(2024), 4 vom: 28. März, Seite 1049-1067 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Pereira, Mariana Pinto [VerfasserIn] |
---|
Links: |
---|
Themen: |
Acute myeloid leukemia |
---|
Anmerkungen: |
Date Completed 15.03.2024 Date Revised 27.03.2024 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1007/s00277-023-05462-5 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM36266837X |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM36266837X | ||
003 | DE-627 | ||
005 | 20240327235326.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1007/s00277-023-05462-5 |2 doi | |
028 | 5 | 2 | |a pubmed24n1350.xml |
035 | |a (DE-627)NLM36266837X | ||
035 | |a (NLM)37770618 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Pereira, Mariana Pinto |e verfasserin |4 aut | |
245 | 1 | 0 | |a TP53-mutated acute myeloid leukemia and myelodysplastic syndrome |b biology, treatment challenges, and upcoming approaches |
264 | 1 | |c 2024 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 15.03.2024 | ||
500 | |a Date Revised 27.03.2024 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. | ||
520 | |a Improved understanding of TP53 biology and the clinicopathological features of TP53-mutated myeloid neoplasms has led to the recognition of TP53-mutated acute myeloid leukemia/myelodysplastic syndrome (TP53m AML/MDS) as a unique entity, characterized by dismal outcomes following conventional therapies. Several clinical trials have investigated combinations of emerging therapies for these patients with the poorest molecular prognosis among myeloid neoplasms. Although some emerging therapies have shown improvement in overall response rates, this has not translated into better overall survival, hence the notion that p53 remains an elusive target. New therapeutic strategies, including novel targeted therapies, immune checkpoint inhibitors, and monoclonal antibodies, represent a shift away from cytotoxic and hypomethylating-based therapies, towards approaches combining non-immune and novel immune therapeutic strategies. The triple combination of azacitidine and venetoclax with either magrolimab or eprenetapopt have demonstrated safety in early trials, with phase III trials currently underway, and promising interim clinical results. This review compiles background on TP53 biology, available and emerging therapies along with their mechanisms of action for the TP53m disease entity, current treatment challenges, and recently published data and status of ongoing clinical trials for TP53m AML/MDS | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Review | |
650 | 4 | |a Acute myeloid leukemia | |
650 | 4 | |a Myelodysplastic syndrome | |
650 | 4 | |a TP53 mutation | |
650 | 4 | |a p53 biology | |
650 | 7 | |a Tumor Suppressor Protein p53 |2 NLM | |
650 | 7 | |a Azacitidine |2 NLM | |
650 | 7 | |a M801H13NRU |2 NLM | |
650 | 7 | |a TP53 protein, human |2 NLM | |
700 | 1 | |a Herrity, Elizabeth |e verfasserin |4 aut | |
700 | 1 | |a Kim, Dennis D H |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Annals of hematology |d 1991 |g 103(2024), 4 vom: 28. März, Seite 1049-1067 |w (DE-627)NLM012918768 |x 1432-0584 |7 nnns |
773 | 1 | 8 | |g volume:103 |g year:2024 |g number:4 |g day:28 |g month:03 |g pages:1049-1067 |
856 | 4 | 0 | |u http://dx.doi.org/10.1007/s00277-023-05462-5 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 103 |j 2024 |e 4 |b 28 |c 03 |h 1049-1067 |