Secondary-Type Mutations in Acute Myeloid Leukemia: Updates from ELN 2022

被引：4

作者：

Bouligny, Ian M. ^{[1
]}

Maher, Keri R. ^{[1
]}

Grant, Steven ^{[1
]}

机构：

[1] Virginia Commonwealth Univ, Dept Internal Med, Div Hematol & Oncol, Massey Canc Ctr, Richmond, VA 23298 USA

来源：

CANCERS | 2023年 / 15卷 / 13期

关键词：

SRSF2; U2AF1; ZRSR2; BCOR; EZH2; STAG2; RUNX1; ASXL1; hematological malignancies; acute myeloid leukemia; COHESIN COMPLEX; SYNTHETIC LETHAL; DOSE-ESCALATION; PHASE-I; THERAPY; TARGET; GENES; RUNX1; CLASSIFICATION; MECHANISMS;

D O I：

10.3390/cancers15133292

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary Therapeutic advances in acute myeloid leukemia (AML) are dependent on identifying and targeting the molecular aberrations that drive disease. The European LeukemiaNet (ELN) 2022 guidelines have improved the categorization of AML into distinct molecular subgroups. One of the most notable recent inclusions is a group of mutations highly specific for secondary AML. This review examines how each of the secondary-type mutations contributes to the genesis of leukemia while spotlighting potential therapeutic avenues. While we highlight the limitations of the ELN 2022 revision, we also emphasize current progress, recent breakthroughs, and novel therapeutic options tailored to each molecular subset. This review provides a background and foundation for rational molecular-based therapeutic approaches and combination strategies to inspire future clinical trial designs. The characterization of the molecular landscape and the advent of targeted therapies have defined a new era in the prognostication and treatment of acute myeloid leukemia. Recent revisions in the European LeukemiaNet 2022 guidelines have refined the molecular, cytogenetic, and treatment-related boundaries between myelodysplastic neoplasms (MDS) and AML. This review details the molecular mechanisms and cellular pathways of myeloid maturation aberrancies contributing to dysplasia and leukemogenesis, focusing on recent molecular categories introduced in ELN 2022. We provide insights into novel and rational therapeutic combination strategies that exploit mechanisms of leukemogenesis, highlighting the underpinnings of splicing factors, the cohesin complex, and chromatin remodeling. Areas of interest for future research are summarized, and we emphasize approaches designed to advance existing treatment strategies.

引用

页数：16

共 92 条

[1] BET inhibitors in the treatment of hematologic malignancies: current insights and future prospects [J].

Abedin, Sameem M. ;

Boddy, Craig S. ;

Munshi, Hidayatullah G. .

ONCOTARGETS AND THERAPY, 2016, 9 :5943-5953

[2] Mutant ASXL1 cooperates with BAP1 to promote myeloid leukaemogenesis [J].

Asada, Shuhei ;

Goyama, Susumu ;

Inoue, Daichi ;

Shikata, Shiori ;

Takeda, Reina ;

Fukushima, Tsuyoshi ;

Yonezawa, Taishi ;

Fujino, Takeshi ;

Hayashi, Yasutaka ;

Kawabata, Kimihito Cojin ;

Fukuyama, Tomofusa ;

Tanaka, Yosuke ;

Yokoyama, Akihiko ;

Yamazaki, Satoshi ;

Kozuka-Hata, Hiroko ;

Oyama, Masaaki ;

Kojima, Shinya ;

Kawazu, Masahito ;

Mano, Hiroyuki ;

Kitamura, Toshio .

NATURE COMMUNICATIONS, 2018, 9

[3] Final results of a phase 2, open-label study of indisulam, idarubicin, and cytarabine in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome [J].

Assi, Rita ;

Kantarjian, Hagop M. ;

Kadia, Tapan M. ;

Pemmaraju, Naveen ;

Jabbour, Elias ;

Jain, Nitin ;

Daver, Naval ;

Estrov, Zeev ;

Uehara, Taisuke ;

Owa, Takashi ;

Cortes, Jorge E. ;

Borthakur, Gautam .

CANCER, 2018, 124 (13) :2758-2765

[4] Phase I Clinical Trial of DNA Methyltransferase Inhibitor Decitabine and PARP Inhibitor Talazoparib Combination Therapy in Relapsed/Refractory Acute Myeloid Leukemia [J].

Baer, Maria R. ;

Kogan, Aksinija A. ;

Bentzen, Soren M. ;

Mi, Tian ;

Lapidus, Rena G. ;

Duong, Vu H. ;

Emadi, Ashkan ;

Niyongere, Sandrine ;

O'Connell, Casey L. ;

Youngblood, Benjamin A. ;

Baylin, Stephen B. ;

Rassool, Feyruz, V .

CLINICAL CANCER RESEARCH, 2022, 28 (07) :1313-1322

[5] Contrasting requirements during disease evolution identify EZH2 as a therapeutic target in AML [J].

Basheer, Faisal ;

Giotopoulos, George ;

Meduri, Eshwar ;

Yun, Haiyang ;

Mazan, Milena ;

Sasca, Daniel ;

Gallipoli, Paolo ;

Marando, Ludovica ;

Gozdecka, Malgorzata ;

Asby, Ryan ;

Sheppard, Olivia ;

Dudek, Monika ;

Bullinger, Lars ;

Doehner, Hartmut ;

Dillon, Richard ;

Freeman, Sylvie ;

Ottmann, Oliver ;

Burnett, Man ;

Russell, Nigel ;

Papaemmanuil, Elli ;

Hills, Robert ;

Campbell, Peter ;

Vassiliou, George S. ;

Huntly, Brian J. P. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2019, 216 (04) :966-981

[6] RUNX1 Mutations in Inherited and Sporadic Leukemia [J].

Bellissimo, Dana C. ;

Speck, Nancy A. .

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2017, 5

[7] Synthetic lethal interaction between the tumour suppressor STAG2 and its paralog STAG1 [J].

Benedetti, Lorena ;

Cereda, Matteo ;

Monteverde, LeeAnn ;

Desai, Nikita ;

Ciccarelli, Francesca D. .

ONCOTARGET, 2017, 8 (23) :37619-37632

[8] Classification and Personalized Prognostic Assessment on the Basis of Clinical and Genomic Features in Myelodysplastic Syndromes [J].

Bersanelli, Matteo ;

Travaglino, Erica ;

Meggendorfer, Manja ;

Matteuzzi, Tommaso ;

Sala, Claudia ;

Mosca, Ettore ;

Chiereghin, Chiara ;

Di Nanni, Noemi ;

Gnocchi, Matteo ;

Zampini, Matteo ;

Rossi, Marianna ;

Maggioni, Giulia ;

Termanini, Alberto ;

Angelucci, Emanuele ;

Bernardi, Massimo ;

Borin, Lorenza ;

Bruno, Benedetto ;

Bonifazi, Francesca ;

Santini, Valeria ;

Bacigalupo, Andrea ;

Voso, Maria Teresa ;

Oliva, Esther ;

Riva, Marta ;

Ubezio, Marta ;

Morabito, Lucio ;

Campagna, Alessia ;

Saitta, Claudia ;

Savevski, Victor ;

Giampieri, Enrico ;

Remondini, Daniel ;

Passamonti, Francesco ;

Ciceri, Fabio ;

Bolli, Niccolo ;

Rambaldi, Alessandro ;

Kern, Wolfgang ;

Kordasti, Shahram ;

Sole, Francesc ;

Palomo, Laura ;

Sanz, Guillermo ;

Santoro, Armando ;

Platzbecker, Uwe ;

Fenaux, Pierre ;

Milanesi, Luciano ;

Haferlach, Torsten ;

Castellani, Gastone ;

Della Porta, Matteo G. .

JOURNAL OF CLINICAL ONCOLOGY, 2021, 39 (11) :1223-+

[9] Mechanisms of myeloid leukemogenesis: Current perspectives and therapeutic objectives [J].

Bouligny, Ian M. ;

Maher, Keri R. ;

Grant, Steven .

BLOOD REVIEWS, 2023, 57

[10]

Bouligny Ian Michael, 2023, J Cell Signal, V4, P1, DOI 10.33696/signaling.4.085

← 1 2 3 4 5 6 7 8 9 10 →