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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

邮发代号 80-967

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Frontiers of Medicine  2023, Vol. 17 Issue (4): 685-698   https://doi.org/10.1007/s11684-022-0942-1
  本期目录
ACSL5, a prognostic factor in acute myeloid leukemia, modulates the activity of Wnt/β-catenin signaling by palmitoylation modification
Wenle Ye1,2, Jinghan Wang1,2, Jiansong Huang1,2, Xiao He3, Zhixin Ma4, Xia Li1,2, Xin Huang1,2, Fenglin Li1,2, Shujuan Huang1,2, Jiajia Pan1,2, Jingrui Jin1,2, Qing Ling1,2, Yungui Wang1,2, Yongping Yu5, Jie Sun1,2(), Jie Jin1,2,6()
1. Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou 310003, China
2. Key Laboratory of Hematopoietic Malignancies, Diagnosis and Treatment, Hangzhou 310009, China
3. Research Centre, Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec H2L 4M1, Canada
4. Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China
5. Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
6. Cancer Center, Zhejiang University, Hangzhou 310058, China
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Abstract：

Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.
Key words： acute myeloid leukemia    acyl-CoA synthetase long chain family member 5    Wnt3a    palmitoylation    ABT-199
收稿日期: 2021-08-23      出版日期: 2023-10-12
Corresponding Author(s): Jie Sun,Jie Jin   
 引用本文:   
. [J]. Frontiers of Medicine, 2023, 17(4): 685-698.
Wenle Ye, Jinghan Wang, Jiansong Huang, Xiao He, Zhixin Ma, Xia Li, Xin Huang, Fenglin Li, Shujuan Huang, Jiajia Pan, Jingrui Jin, Qing Ling, Yungui Wang, Yongping Yu, Jie Sun, Jie Jin. ACSL5, a prognostic factor in acute myeloid leukemia, modulates the activity of Wnt/β-catenin signaling by palmitoylation modification. Front. Med., 2023, 17(4): 685-698.
 链接本文:  
https://academic.hep.com.cn/fmd/CN/10.1007/s11684-022-0942-1
https://academic.hep.com.cn/fmd/CN/Y2023/V17/I4/685
Fig.1  
Variables Low expression High expression P value
Number (%) 156 (50.00) 156 (50.00)
ACSL5 expression 0.42 (0.27, 0.64) 1.22 (1.09, 1.64) < 0.0001
Age, median (range), year 51.00 (41.00, 61.00) 58.00 (37.00, 66.00) 0.1577
Male, n (%) 104 (66.67) 93 (59.62) 0.6812
aWBC, median (bIQR), ×109/L 10.65 (2.30, 56.30) 13.10 (2.80, 54.00) 0.5373
cHB, median (IQR), ×109/L 88.00 (69.00, 105.00) 84.00 (67.00, 102.00) 0.1241
dPLT, median (IQR), ×109/L 52.00 (26.75, 90.75) 50.00 (27.75, 90.00) 0.9750
Blast, median (IQR), ×109/L 65.00 (40.00,82.00) 69.00 (48.00,81.00) 0.2390
eFAB classification, n (%) 0.2934
M0 17 (10.90) 20 (12.82)
M1 12 (7.69) 15 (9.62)
M2 78 (50.00) 73 (46.79)
M3 0 0
M4 10 (6.41) 3 (1.92)
M5 34 (21.79) 43 (27.56)
M6 5 (3.21) 2 (1.28)
Genes mutations, n (%)
FLT3-ITD 26 (16.67) 35 (22.44) 0.6936
NPM1 41 (26.28) 42 (26.92) 0.3136
DNMT3A 16 (10.26) 20 (12.82) 0.6940
f CEBPADM 23 (14.74) 24 (15.38) 0.4400
IDH1 32 (20.51) 24 (15.38) 0.8987
IDH2 15 (9.62) 26 (16.67) 0.6859
gTreatment (%) 0.4445
DA 39 (25.00) 36 (23.08)
HAA 34 (21.79) 17 (18.90)
IA 83 (53.20) 103 (66.03)
CR (%) 98 (62.82) 82 (52.56) 0.5097
Tab.1  
Variables Overall survival Event free survival
HR (95% CI) P HR (95% CI) P
ACSL5 expression (high vs. low) 1.932 (1.253, 2.979) 0.003 1.544 (1.040, 2.293) 0.031
Age (> 60) 2.191 (1.407, 3.413) < 0.001 2.194 (1.455, 3.308) < 0.001
WBC (> 10) 1.283 (0.836, 1.968) 0.254 1.487 (0.994, 2.224) 0.053
FLT3-ITD 2.332 (1.454, 3.740) < 0.001 1.933 (1.240, 3.014) 0.004
NPM1 0.726 (0.447, 1.179) 0.196 0.838 (0.536, 1.309) 0.437
DNMT3a 1.839 (1.086, 3.115) 0.023 1.693 (1.030, 2.785) 0.038
CEBPA 0.286 (0.122, 0.670) 0.004 0.271 (0.123, 0.596) 0.001
IDH1 1.420 (0.827, 2.439) 0.204 1.631 (0.991, 2.685) 0.054
IDH2 1.160 (0.604, 2.226) 0.656 1.089 (0.594, 1.995) 0.078
Treatment protocols 1.098 (0.776, 1.553) 0.596 0.957 (0.688, 1.330) 0.792
Tab.2  
Fig.2  
Fig.3  
Fig.4  
Fig.5  
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