Mechanisms of Resistance to Small Molecules in Acute Myeloid Leukemia

被引：9

作者：

Lang, Tonio Johannes Lukas ^{[1
,2
,3
]}

Damm, Frederik ^{[1
,2
,3
,4
,5
]}

Bullinger, Lars ^{[1
,2
,3
,4
,5
]}

Frick, Mareike ^{[1
,2
,3
,4
,5
]}

机构：

[1] Charite Univ Med Berlin, Dept Hematol Oncol & Canc Immunol, D-13353 Berlin, Germany

[2] Free Univ Berlin, D-13353 Berlin, Germany

[3] Humboldt Univ, D-13353 Berlin, Germany

[4] German Canc Consortium DKTK, D-69120 Heidelberg, Germany

[5] German Canc Res Ctr, D-69120 Heidelberg, Germany

来源：

CANCERS | 2023年 / 15卷 / 18期

关键词：

AML; small molecule; gene mutations; resistance; FLT3; IDH1/IDH2; BCL2; venetoclax; targeted therapy; precision medicine; RECEPTOR TYROSINE KINASE; MYELODYSPLASTIC SYNDROMES; PROMOTES RESISTANCE; CONFER RESISTANCE; FLT3; INHIBITORS; BCL-2; PROTEIN; AML CELLS; MUTATIONS; EXPRESSION; THERAPY;

D O I：

10.3390/cancers15184573

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary Acute myeloid leukemia (AML) is a dangerous cancer of the blood. In recent years, a series of drugs was approved to specifically target misdirected processes in the cancerous cells. These so-called "small molecules" substantially improved therapeutic outcomes, but eventually leukemia returns in most patients. In this review, we summarize the current state of knowledge regarding the mechanisms that lead to failure of the most frequently used new therapies and introduce potential strategies to overcome the mechanisms associated with disease recurrence.Abstract In recent years, great progress has been made in the therapy of AML by targeting cellular processes associated with specific molecular features of the disease. Various small molecules inhibiting FLT3, IDH1/IDH2, and BCL2 have already gained approval from the respective authorities and are essential parts of personalized therapeutic regimens in modern therapy of AML. Unfortunately, primary and secondary resistance to these inhibitors is a frequent problem. Here, we comprehensively review the current state of knowledge regarding molecular processes involved in primary and secondary resistance to these agents, covering both genetic and nongenetic mechanisms. In addition, we introduce concepts and strategies for how these resistance mechanisms might be overcome.

引用

页数：19

共 134 条

[1] GENOMIC STRUCTURE OF THE DOWNSTREAM PART OF THE HUMAN FLT3 GENE - EXON/INTRON STRUCTURE CONSERVATION AMONG GENES ENCODING RECEPTOR TYROSINE KINASES (RTK) OF SUBCLASS-III [J].

AGNES, F ;

SHAMOON, B ;

DINA, C ;

ROSNET, O ;

BIRNBAUM, D ;

GALIBERT, F .

GENE, 1994, 145 (02) :283-288

[2] Association of leukemia genetics with response to venetoclax and hypomethylating agents in relapsed/refractory acute myeloid leukemia [J].

Aldoss, Ibrahim ;

Yang, Dongyun ;

Pillai, Raju ;

Sanchez, James F. ;

Mei, Matthew ;

Aribi, Ahmed ;

Ali, Haris ;

Sandhu, Karamjeet ;

Al Malki, Monzr M. ;

Salhotra, Amandeep ;

Khaled, Samer ;

Sun, Weili ;

O'Donnell, Margaret ;

Snyder, David ;

Nakamura, Ryotaro ;

Stein, Anthony S. ;

Forman, Stephen J. ;

Marcucci, Guido ;

Pullarkat, Vinod .

AMERICAN JOURNAL OF HEMATOLOGY, 2019, 94 (10) :E253-E255

[3] Patterns of Resistance Differ in Patients with Acute Myeloid Leukemia Treated with Type I versus Type II FLT3 Inhibitors [J].

Alotaibi, Ahmad S. ;

Yilmaz, Musa ;

Kanagal-Shamanna, Rashmi ;

Loghavi, Sanam ;

Kadia, Tapan M. ;

DiNardo, Courtney D. ;

Borthakur, Gautam ;

Konopleva, Marina ;

Pierce, Sherry A. ;

Wang, Sa A. ;

Tang, Guilin ;

Guerra, Veronica ;

Samra, Bachar ;

Pemmaraju, Naveen ;

Jabbour, Elias ;

Short, Nicholas J. ;

Issa, Ghayas C. ;

Ohanian, Maro ;

Garcia-Manero, Guillermo ;

Bhalla, Kapil N. ;

Patel, Keyur P. ;

Takahashi, Koichi ;

Andreeff, Michael ;

Cortes, Jorge E. ;

Kantarjian, Hagop M. ;

Ravandi, Farhad ;

Daver, Naval .

BLOOD CANCER DISCOVERY, 2021, 2 (02) :125-134

[4] Enasidenib induces acute myeloid leukemia cell differentiation to promote clinical response [J].

Amatangelo, Michael D. ;

Quek, Lynn ;

Shih, Alan ;

Stein, Eytan M. ;

Roshal, Mikhail ;

David, Muriel D. ;

Marteyn, Benoit ;

Farnoud, Noushin Rahnamay ;

de Botton, Stephane ;

Bernard, Olivier A. ;

Wu, Bin ;

Yen, Katharine E. ;

Tallman, Martin S. ;

Papaemmanuil, Elli ;

Penard-Lacronique, Virginie ;

Thakurta, Anjan ;

Vyas, Paresh ;

Levine, Ross L. .

BLOOD, 2017, 130 (06) :732-741

[5] FLT3 inhibitors in acute myeloid leukemia: ten frequently asked questions [J].

Antar, Ahmad I. ;

Otrock, Zaher K. ;

Jabbour, Elias ;

Mohty, Mohamad ;

Bazarbachi, Ali .

LEUKEMIA, 2020, 34 (03) :682-696

[6] International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data [J].

Arber, Daniel A. ;

Orazi, Attilio ;

Hasserjian, Robert P. ;

Borowitz, Michael J. ;

Calvo, Katherine R. ;

Kvasnicka, Hans-Michael ;

Wang, Sa A. ;

Bagg, Adam ;

Barbui, Tiziano ;

Branford, Susan ;

Bueso-Ramos, Carlos E. ;

Cortes, Jorge E. ;

Dal Cin, Paola ;

DiNardo, Courtney D. ;

Dombret, Herve ;

Duncavage, Eric J. ;

Ebert, Benjamin L. ;

Estey, Elihu H. ;

Facchetti, Fabio ;

Foucar, Kathryn ;

Gangat, Naseema ;

Gianelli, Umberto ;

Godley, Lucy A. ;

Gokbuget, Nicola ;

Gotlib, Jason ;

Hellstrom-Lindberg, Eva ;

Hobbs, Gabriela S. ;

Hoffman, Ronald ;

Jabbour, Elias J. ;

Kiladjian, Jean-Jacques ;

Larson, Richard A. ;

Le Beau, Michelle M. ;

Loh, Mignon L. -C. ;

Lowenberg, Bob ;

Macintyre, Elizabeth ;

Malcovati, Luca ;

Mullighan, Charles G. ;

Niemeyer, Charlotte ;

Odenike, Olatoyosi M. ;

Ogawa, Seishi ;

Orfao, Alberto ;

Papaemmanuil, Elli ;

Passamonti, Francesco ;

Porkka, Kimmo ;

Pui, Ching-Hon ;

Radich, Jerald P. ;

Reiter, Andreas ;

Rozman, Maria ;

Rudelius, Martina ;

Savona, Michael R. .

BLOOD, 2022, 140 (11) :1200-1228

[7] Endothelial E-selectin inhibition improves acute myeloid leukaemia therapy by disrupting vascular niche-mediated chemoresistance [J].

Barbier, Valerie ;

Erbani, Johanna ;

Fiveash, Corrine ;

Davies, Julie M. ;

Tay, Joshua ;

Tallack, Michael R. ;

Lowe, Jessica ;

Magnani, John L. ;

Pattabiraman, Diwakar R. ;

Perkins, Andrew C. ;

Lisle, Jessica ;

Rasko, John E. J. ;

Levesque, Jean-Pierre ;

Winkler, Ingrid G. .

NATURE COMMUNICATIONS, 2020, 11 (01)

[8]

BENSI L, 1995, HAEMATOLOGICA, V80, P98

[9] Genetic characterization of ABT-199 sensitivity in human AML [J].

Bisaillon, Richard ;

Moison, Celine ;

Thiollier, Clarisse ;

Krosl, Jana ;

Bordeleau, Marie-Eve ;

Lehnertz, Bernhard ;

Lavallee, Vincent-Philippe ;

MacRae, Tara ;

Mayotte, Nadine ;

Labelle, Caroline ;

Boucher, Genevieve ;

Spinella, Jean-Francois ;

Boivin, Isabel ;

D'Angelo, Giovanni ;

Lavallee, Sylvie ;

Marinier, Anne ;

Lemieux, Sebastien ;

Hebert, Josee ;

Sauvageau, Guy .

LEUKEMIA, 2020, 34 (01) :63-74

[10] A novel molecular mechanism of primary resistance to FLT3-kinase inhibitors in AML [J].

Breitenbuecher, Frank ;

Markova, Boyka ;

Kasper, Stefan ;

Carius, Birgit ;

Stauder, Torsten ;

Boehmer, Frank D. ;

Masson, Kristina ;

Ronnstrand, Lars ;

Huber, Christoph ;

Kindler, Thomas ;

Fischer, Thomas .

BLOOD, 2009, 113 (17) :4063-4073

← 1 2 3 4 5 6 7 8 9 10 →