TP53 Mutant Acute Myeloid Leukemia: The Immune and Metabolic Perspective

被引:0
作者
Zingarelli, Federico [1 ]
Zannoni, Letizia [1 ]
Curti, Antonio [2 ]
机构
[1] Univ Bologna, Dipartimento Med Specialist Diagnost & Sperimental, I-40138 Bologna, Italy
[2] IRCCS Azienda Osped Univ Bologna, Ist Ematol Seragnoli, I-40138 Bologna, Italy
来源
HEMATO | 2022年 / 3卷 / 04期
关键词
acute myeloid leukemia; TP53; mutation; metabolism; immunotherapy; COMPLEX KARYOTYPE; STEM-CELLS; PHASE-II; P53; MUTATIONS; INHIBITION; VENETOCLAX; GENE; AZACITIDINE; EXPRESSION;
D O I
10.3390/hemato3040050
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
TP53 mutated/deleted acute myeloid leukemia (AML) stands out as one of the poorest prognosis forms of acute leukemia with a median overall survival not reaching one year in most cases, even in selected cases when allogenic stem-cell transplantation is performed. This aggressive behavior relies on intrinsic chemoresistance of blast cells and on high rates of relapse. New insights into the biology of the disease have shown strong linkage between TP53 mutant AML, altered metabolic features and immunoregulation uncovering new scenarios and leading to possibilities beyond current treatment approaches. Furthermore, new targeted therapies acting on misfolded/dysfunctional p53 protein are under current investigation with the aim to improve outcomes. In this review, we sought to offer an insight into TP53 mutant AML current biology and treatment approaches, with a special focus on leukemia-associated immune and metabolic changes.
引用
收藏
页码:742 / 757
页数:16
相关论文
共 88 条
  • [1] Immune Checkpoint Inhibition in Acute Myeloid Leukemia and Myelodysplastic Syndromes
    Abaza, Yasmin
    Zeidan, Amer M.
    [J]. CELLS, 2022, 11 (14)
  • [2] Efficacy of the combination of venetoclax and hypomethylating agents in relapsed/refractory acute myeloid leukemia
    Aldoss, Ibrahim
    Yang, Dongyun
    Aribi, Ahmed
    Ali, Haris
    Sandhu, Karamjeet
    Al Malki, Monzr M.
    Mei, Matthew
    Salhotra, Amandeep
    Khaled, Samer
    Nakamura, Ryotaro
    Snyder, David
    O'Donnell, Margaret
    Stein, Anthony S.
    Forman, Stephen J.
    Marcucci, Guido
    Pullarkat, Vinod
    [J]. HAEMATOLOGICA, 2018, 103 (09) : E404 - E407
  • [3] The BCL2 selective inhibitor venetoclax induces rapid onset apoptosis of CLL cells in patients via a TP53-independent mechanism
    Anderson, Mary Ann
    Deng, Jing
    Seymour, John F.
    Tam, Constantine
    Kim, Su Young
    Fein, Joshua
    Yu, Lijian
    Brown, Jennifer R.
    Westerman, David
    Si, Eric G.
    Majewski, Ian J.
    Segal, David
    Enschede, Sari L. Heitner
    Huang, David C. S.
    Davids, Matthew S.
    Letai, Anthony
    Roberts, Andrew W.
    [J]. BLOOD, 2016, 127 (25) : 3215 - 3224
  • [4] Why are there hotspot mutations in the TP53 gene in human cancers?
    Baugh, Evan H.
    Ke, Hua
    Levine, Arnold J.
    Bonneau, Richard A.
    Chan, Chang S.
    [J]. CELL DEATH AND DIFFERENTIATION, 2018, 25 (01) : 154 - 160
  • [5] Bernard Elsa, 2022, NEJM Evid, V1, pEVIDoa2200008, DOI 10.1056/EVIDoa2200008
  • [6] APR-246 induces early cell death by ferroptosis in acute myeloid leukemia
    Birsen, Rudy
    Larrue, Clement
    Decroocq, Justine
    Johnson, Natacha
    Guiraud, Nathan
    Gotanegre, Mathilde
    Cantero-Aguilar, Lilia
    Grignano, Eric
    Huynh, Tony
    Fontenay, Michaela
    Kosmider, Olivier
    Mayeux, Patrick
    Chapuis, Nicolas
    Sarry, Jean Emmanuel
    Tamburini, Jerome
    Bouscary, Didier
    [J]. HAEMATOLOGICA, 2022, 107 (02) : 403 - 416
  • [7] p53, cancer and the immune response
    Blagih, Julianne
    Buck, Michael D.
    Vousden, Karen H.
    [J]. JOURNAL OF CELL SCIENCE, 2020, 133 (05)
  • [8] TP53 gene mutation is frequent in patients with acute myeloid leukemia and complex karyotype, and is associated with very poor prognosis
    Bowen, D.
    Groves, M. J.
    Burnett, A. K.
    Patel, Y.
    Allen, C.
    Green, C.
    Gale, R. E.
    Hills, R.
    Linch, D. C.
    [J]. LEUKEMIA, 2009, 23 (01) : 203 - 206
  • [9] Efficacy and Safety of Sabatolimab (MBG453) in Combination with Hypomethylating Agents (HMAs) in Patients (Pts) with Very High/High-Risk Myelodysplastic Syndrome (vHR/HRMDS) and Acute Myeloid Leukemia (AML): Final Analysis from a Phase Ib Study
    Brunner, Andrew M.
    Esteve, Jordi
    Porkka, Kimmo
    Knapper, Steve
    Traer, Elie
    Scholl, Sebasttian
    Garcia-Manero, Guillermo
    Vey, Norbert
    Wermke, Martin
    Janssen, Jeroen
    Narayan, Rupa
    Loo, Sun
    Kontro, Mika
    Ottmann, Oliver
    Naidu, Purushotham
    Pelletier, Marc
    Han, May
    Lewandowski, Andrew
    Zhang, Na
    Mohammed, Anisha
    Rinne, Mikael L.
    Borate, Uma
    Wei, Andrew H.
    Tovar, Natalia
    [J]. BLOOD, 2021, 138
  • [10] P63 and P73 Activation in Cancers with p53 Mutation
    Cai, Bi-He
    Hsu, Yun-Chien
    Yeh, Fang-Yu
    Lin, Yu-Rou
    Lu, Rui-Yu
    Yu, Si-Jie
    Shaw, Jei-Fu
    Wu, Ming-Han
    Tsai, Yi-Zhen
    Lin, Ying-Chen
    Bai, Zhi-Yu
    Shih, Yu-Chen
    Hsu, Yi-Chiang
    Liao, Ruo-Yu
    Kuo, Wei-Hsin
    Hsu, Chao-Tien
    Lien, Ching-Feng
    Chen, Chia-Chi
    [J]. BIOMEDICINES, 2022, 10 (07)