All-trans retinoic acid exerts selective anti-FLT3-ITD acute myeloid leukemia efficacy through downregulating Chk1 kinase

被引：8

作者：

Wang, Wenliang ^{[1
,2
]}

Jiang, Zongru ^{[1
,2
]}

Wang, Li ^{[1
,2
]}

Wang, Aoli ^{[1
]}

Liu, Juan ^{[1
,2
]}

Chen, Cheng ^{[1
,2
]}

Yu, Kailin ^{[1
]}

Zou, Fengming ^{[1
]}

Wang, Wenchao ^{[1
,3
]}

Liu, Jing ^{[1
,3
]}

Liu, Qingsong ^{[1
,2
,3
,4
]}

机构：

[1] Chinese Acad Sci, Hefei Inst Phys Sci, High Magnet Field Lab, Key Lab High Magnet Field & Ion Beam Phys Biol, Hefei 230031, Anhui, Peoples R China

[2] Univ Sci & Technol China, Hefei 230036, Anhui, Peoples R China

[3] Precis Med Res Lab Anhui Prov, Hefei 230088, Anhui, Peoples R China

[4] Anhui Univ, Minist Educ, Key Lab Struct & Funct Regulat Hybrid Mat, Inst Phys Sci & Informat Technol, Hefei 230601, Anhui, Peoples R China

来源：

CANCER LETTERS | 2020年 / 473卷

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

ATRA; Acute myeloid leukemia; DNA damage repair; SN38; Combination therapy; INTERNAL TANDEM DUPLICATION; DNA-DAMAGE RESPONSE; POOR-PROGNOSIS; IN-VITRO; FLT3; CANCER; CELLS; MUTATIONS; SURVIVAL; HISAT;

D O I：

10.1016/j.canlet.2019.12.045

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

All-trans retinoic acid (ATRA) is known to be a potent inhibitor of FLT3-ITD acute myeloid leukemia (AML) cells, although the exact mechanism remains unclear. In this work, we report that ATRA causes fatal mitotic catastrophe in FLT3-ITD AML cells by degrading Chk1 kinase, and therefore preventing DNA damage repair. In order to explore a further enhancement in the inhibitory effect of ATRA on FLT3-ITD AML cells, we investigated the suitability of a combination of ATRA and DNA damage drug SN38. In vitro experiments showed that this combinatorial approach effectively inhibited the proliferation of FLT3-ITD cells and induced cell apoptosis in AML. In vivo experiments confirmed that the combination could substantially improve the anti-tumor effect of SN38. Taken together, our results indicate that ATRA down-regulates Chk1 in FLT3-ITD AML cells, and the combination of ATRA and SN38 significantly improves the anti-tumor effect of either ATRA or SN38 when used alone.

引用

页码：130 / 138

页数：9

共 34 条

[1] Differential response of human acute myeloid leukemia cells to gemtuzumab ozogamicin in vitro: role of Chk1 and Chk2 phosphorylation and caspase 3 [J].

Amico, D ;

Barbui, AM ;

Erba, E ;

Rambaldi, A ;

Introna, M ;

Golay, J .

BLOOD, 2003, 101 (11) :4589-4597

[2]

Barnum KJ, 2014, METHODS MOL BIOL, V1170, P29, DOI 10.1007/978-1-4939-0888-2_2

[3] Multiomic Analysis of the UV-Induced DNA Damage Response [J].

Boeing, Stefan ;

Williamson, Laura ;

Encheva, Vesela ;

Gori, Ilaria ;

Saunders, Rebecca E. ;

Instrell, Rachael ;

Aygun, Ozan ;

Rodriguez-Martinez, Marta ;

Weems, Juston C. ;

Kelly, Gavin P. ;

Conaway, Joan W. ;

Conaway, Ronald C. ;

Stewart, Aengus ;

Howell, Michael ;

Snijders, Ambrosius P. ;

Svejstrup, Jesper Q. .

CELL REPORTS, 2016, 15 (07) :1597-1610

[4] Constitutive Activation of the DNA Damage Signaling Pathway in Acute Myeloid Leukemia with Complex Karyotype: Potential Importance for Checkpoint Targeting Therapy [J].

Cavelier, Cindy ;

Didier, Christine ;

Prade, Nais ;

Mas, Veronique Mansat-De ;

Manenti, Stephane ;

Recher, Christian ;

Demur, Cecile ;

Ducommun, Bernard .

CANCER RESEARCH, 2009, 69 (22) :8652-8661

[5] Retinoic acid synthesis and functions in early embryonic development [J].

Kam, Richard Kin Ting ;

Deng, Yi ;

Chen, Yonglong ;

Zhao, Hui .

CELL AND BIOSCIENCE, 2012, 2

[6] CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML) [J].

Kelly, LM ;

Yu, JC ;

Boulton, CL ;

Apatira, M ;

Li, J ;

Sullivan, CM ;

Williams, I ;

Amaral, SM ;

Curley, DP ;

Duclos, N ;

Neuberg, D ;

Scarborough, RM ;

Pandey, A ;

Hollenbach, S ;

Abe, K ;

Lokker, NA ;

Gilliland, DG ;

Giese, NA .

CANCER CELL, 2002, 1 (05) :421-432

[7] Comprehensive analysis of genetic alterations and their prognostic impacts in adult acute myeloid leukemia patients [J].

Kihara, R. ;

Nagata, Y. ;

Kiyoi, H. ;

Kato, T. ;

Yamamoto, E. ;

Suzuki, K. ;

Chen, F. ;

Asou, N. ;

Ohtake, S. ;

Miyawaki, S. ;

Miyazaki, Y. ;

Sakura, T. ;

Ozawa, Y. ;

Usui, N. ;

Kanamori, H. ;

Kiguchi, T. ;

Imai, K. ;

Uike, N. ;

Kimura, F. ;

Kitamura, K. ;

Nakaseko, C. ;

Onizuka, M. ;

Takeshita, A. ;

Ishida, F. ;

Suzushima, H. ;

Kato, Y. ;

Miwa, H. ;

Shiraishi, Y. ;

Chiba, K. ;

Tanaka, H. ;

Miyano, S. ;

Ogawa, S. ;

Naoe, T. .

LEUKEMIA, 2014, 28 (08) :1586-1595

[8]

Kim D, 2015, NAT METHODS, V12, P357, DOI [10.1038/NMETH.3317, 10.1038/nmeth.3317]

[9] FLT3: ITDoes matter in leukemia [J].

Levis, M ;

Small, D .

LEUKEMIA, 2003, 17 (09) :1738-1752

[10] Death by releasing the breaks: CHK1 inhibitors as cancer therapeutics [J].

Ma, Cynthia X. ;

Janetka, James W. ;

Piwnica-Worms, Helen .

TRENDS IN MOLECULAR MEDICINE, 2011, 17 (02) :88-96

← 1 2 3 4 →