General Information of the Disease (ID: DIS00011)
Name
Acute myeloid leukaemia
ICD
ICD-11: 2A60
Full List of Target(s) of This Ferroptosis-centered Disease
Long-chain-fatty-acid--CoA ligase 1 (ACSL1)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Driver
Responsed Disease Acute myeloid leukemia [ICD-11: 2A60]
Responsed Drug GSK3368715 Phase 1
Responsed Regulator Protein arginine N-methyltransferase 1 (PRMT1) Suppressor
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model NB4 cells Acute promyelocytic leukemia Homo sapiens CVCL_0005
HEL cells Erythroleukemia Homo sapiens CVCL_0001
MOLM-13 cells Adult acute myeloid leukemia Homo sapiens CVCL_2119
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
5 x 106 NB4 cells were subcutaneously injected into the flank of 6-7-week-old female nude mice. The tumor number, body weight, and tumor volume were measured every other day. Tumor volumes were estimated using the following formula: tumor volume = (length x width2)/2. When tumor volumes reached 100-200 mm3, the mice were randomly divided into solvent control, RSL3, GSK3368715, or RSL3 + GSK3368715 combination groups (six mice per group). Specifically, for the RSL3 group, mice received intraperitoneal injections of RSL3 at 50 mg/kg 2 days apart. In the GSK3368715 group, GSK3368715 was intraperitoneally injected into mice at a dose of 75 mg/kg for 2 consecutive days per week. For the group that received RSL3 + GSK3368715 combination treatment, GSK3368715 (75 mg/kg) was administered by intraperitoneal injection for the first 2 days. Immediately thereafter, the mice received an intraperitoneal injection of RSL3 (50 mg/kg) 2 days apart. After 1 day of rest, the cycle was repeated until the end of the study on Day 21. Tumor volumes and body weights of the mice were measured and recorded every other day.

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Response regulation Both GSK3368715 and PRMT1 knockout upregulated acyl-CoA synthetase long-chain family member 1 (ACSL1), which acts as a ferroptosis promoter by increasing lipid peroxidation. Knockout ACSL1 reduced the ferroptosis sensitivity of Acute myeloid leukemia (AML) cells following GSK3368715 treatment. Overall, PRMT1 inhibition promotes ferroptosis sensitivity via ACSL1 upregulation in acute myeloid leukemia.
Unspecific Target
In total 7 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Responsed Disease Acute myeloid leukemia [ICD-11: 2A60]
Responsed Drug Dihydroartemisinin Investigative
Responsed Regulator 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
Cell proliferation
Cell cycle
In Vitro Model HL-60 cells Adult acute myeloid leukemia Homo sapiens CVCL_0002
KG1 cells Normal Mus musculus CVCL_UD72
THP-1 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0006
In Vivo Model
BALB/c Nude Mice (4 weeks old) were obtained from Shanghai Experimental Animal Center of the Chinese Academy of Sciences (Shanghai, China) and then subcutaneously injection with HL60 cells (1 x 107, suspended in 0.1 mL PBS). After tumors reached 100-200 mm3, the mice were randomly assigned to two groups. DHA was administered intraperitoneal injection once a day at 50 mg/kg body weight and the mice in normal control were received equal amounts of vehicle (10% DMSO in sterile corn oil). On the 28th day, mice were euthanized. The tumor volumes were measured every 4 days with a caliper.

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Response regulation Dihydroartemisinin (DHA) strongly inhibited the viability of acute myeloid leukemia (AML) cell lines and arrest cell cycle at G0/G1 phase. Mechanistically, DHA induced autophagy by regulating the activity of AMPK/mTOR/p70S6k signaling pathway, which accelerated the degradation of ferritin, increased the labile iron pool, promoted the accumulation of cellular ROS and eventually led to ferroptotic cell death.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [3]
Responsed Disease Acute myeloid leukemia [ICD-11: 2A60]
Responsed Drug Dihydroartemisinin Investigative
Responsed Regulator Metallothionein-1A (MT1A) .
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model MOLM-14 cells Leukemia Homo sapiens CVCL_7916
OCI-AML-2 cells Acute myeloid leukemia Homo sapiens CVCL_1619
HL-60 cells Adult acute myeloid leukemia Homo sapiens CVCL_0002
SET-2 cells Acute megakaryoblastic leukemia Homo sapiens CVCL_2187
MV4-11 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0064
K-562 cells Chronic myelogenous leukemia Homo sapiens CVCL_0004
THP-1 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0006
UT-7/Epo cells Acute megakaryoblastic leukemia Homo sapiens CVCL_5202
SKM-1 cells Acute myeloid leukemia Homo sapiens CVCL_0098
NB4 cells Acute promyelocytic leukemia Homo sapiens CVCL_0005
Kasumi-1 cells Acute myeloid leukemia Homo sapiens CVCL_0589
Response regulation Dihydroartemisinin (DHA) activated zinc metabolism signaling, especially the upregulation of metallothionein (MT). DHA activates ferritinophagy and subsequent ferroptosis in AML and that MTs are involved in glutathione regenerating and antioxidant response in Acute Myeloid Leukemia.
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target [4]
Responsed Disease Acute myeloid leukemia [ICD-11: 2A60]
Responsed Drug Typhaneoside Investigative
Responsed Regulator 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1) Driver
Pathway Response Ferroptosis hsa04216
Apoptosis hsa04210
Autophagy hsa04140
AMPK signaling pathway hsa04152
Cell Process Cell ferroptosis
Cell proliferation
Cell apoptosis
Cell autophagy
In Vitro Model KAS-6/1 cells Plasma cell myeloma Homo sapiens CVCL_9544
HL-60 cells Adult acute myeloid leukemia Homo sapiens CVCL_0002
NB4 cells Acute promyelocytic leukemia Homo sapiens CVCL_0005
K-562 cells Chronic myelogenous leukemia Homo sapiens CVCL_0004
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
4-week-old BALB/c malenude mice(Peking University Health Science Center, Beijing, China) were subcutaneously injection with HL60 cells (1 x 107). After tumor volume reached 50 mm3, mice were randomly divided into 4 groups (n = 16/group). TYP was administered intraperitoneal injection once a day at 10, 20 and 30 mg/kg body weight and the mice in normal control group were received equal amounts of 10% DMSO in sterile corn oil.

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Response regulation Typhaneoside (TYP) significantly triggered autophagy in acute myeloid leukemia (AML) cells by promoting the activation of AMP-activated protein kinase (AMPK) signaling, contributing to ferritin degradation, ROS accumulation and ferroptotic cell death ultimately.
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target [13]
Responsed Disease Acute myeloid leukemia [ICD-11: 2A60]
Responsed Regulator Basic helix-loop-helix ARNT-like protein 1 (BMAL1) Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model MOLM-13 cells Adult acute myeloid leukemia Homo sapiens CVCL_2119
Response regulation ARNTL expression is closely associated with tumor-infiltrating immune cells like the macrophages and NK cells. Inhibiting the ARNTL expression suppressed colony formation and induced ferroptosis in acute myeloid leukemia (AML) cells.
Experiment 5 Reporting the Ferroptosis-centered Disease Response by This Target [14]
Responsed Disease Acute myeloid leukemia [ICD-11: 2A60]
Responsed Regulator CircKDM4C (circRNA) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model hBMSCs (Bone marrow stromal cells)
K-562 cells Chronic myelogenous leukemia Homo sapiens CVCL_0004
THP-1 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0006
HL-60 cells Adult acute myeloid leukemia Homo sapiens CVCL_0002
MOLM-13 cells Adult acute myeloid leukemia Homo sapiens CVCL_2119
In Vivo Model
All BALB/C male nude mice (6 weeks old), purchased from Beijing Weitong lihua Experimental Animal Technology Co., Ltd, were maintained in pathogen-free facilities. The K562 or HL-60 cells (3 x 106, 200 ul) transfected with circKDM4C, vector, si-NC, or si-circKDM4C were subcutaneously injected into the right flank of nude mice (9 mice each group) for tumorigenesis. The maximum (Length) and minimum (Width) length of the tumors were measured.

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Response regulation The overexpression of circKDM4C in AML cell lines inhibited the cell proliferation, migration, invasion, and promoted ferroptosis. The expression of circKDM4C and hsa-let-7b-5p are negatively correlated, while circKDM4C and p53 are positively correlated to acute myeloid leukemia (AML) patients. Moreover, circKDM4C induces ferroptosis by sponging hsa-let-7b-5p which upregulates the expression of P53.
Experiment 6 Reporting the Ferroptosis-centered Disease Response by This Target [14]
Responsed Disease Acute myeloid leukemia [ICD-11: 2A60]
Responsed Regulator hsa-let-7b-5p (miRNA) Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model hBMSCs (Bone marrow stromal cells)
K-562 cells Chronic myelogenous leukemia Homo sapiens CVCL_0004
THP-1 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0006
HL-60 cells Adult acute myeloid leukemia Homo sapiens CVCL_0002
MOLM-13 cells Adult acute myeloid leukemia Homo sapiens CVCL_2119
In Vivo Model
All BALB/C male nude mice (6 weeks old), purchased from Beijing Weitong lihua Experimental Animal Technology Co., Ltd, were maintained in pathogen-free facilities. The K562 or HL-60 cells (3 x 106, 200 ul) transfected with circKDM4C, vector, si-NC, or si-circKDM4C were subcutaneously injected into the right flank of nude mice (9 mice each group) for tumorigenesis. The maximum (Length) and minimum (Width) length of the tumors were measured.

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Response regulation The overexpression of circKDM4C in acute myeloid leukemia (AML) cell lines inhibited the cell proliferation, migration, invasion, and promoted ferroptosis. The expression of circKDM4C and hsa-let-7b-5p are negatively correlated, while circKDM4C and p53 are positively correlated to AML patients. Moreover, circKDM4C induces ferroptosis by sponging hsa-let-7b-5p which upregulates the expression of P53.
Experiment 7 Reporting the Ferroptosis-centered Disease Response by This Target [14]
Responsed Disease Acute myeloid leukemia [ICD-11: 2A60]
Responsed Regulator Cellular tumor antigen p53 (TP53) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model hBMSCs (Bone marrow stromal cells)
K-562 cells Chronic myelogenous leukemia Homo sapiens CVCL_0004
THP-1 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0006
HL-60 cells Adult acute myeloid leukemia Homo sapiens CVCL_0002
MOLM-13 cells Adult acute myeloid leukemia Homo sapiens CVCL_2119
In Vivo Model
All BALB/C male nude mice (6 weeks old), purchased from Beijing Weitong lihua Experimental Animal Technology Co., Ltd, were maintained in pathogen-free facilities. The K562 or HL-60 cells (3 x 106, 200 ul) transfected with circKDM4C, vector, si-NC, or si-circKDM4C were subcutaneously injected into the right flank of nude mice (9 mice each group) for tumorigenesis. The maximum (Length) and minimum (Width) length of the tumors were measured.

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Response regulation The overexpression of circKDM4C in acute myeloid leukemia (AML) cell lines inhibited the cell proliferation, migration, invasion, and promoted ferroptosis. The expression of circKDM4C and hsa-let-7b-5p are negatively correlated, while circKDM4C and p53 are positively correlated to AML patients. Moreover, circKDM4C induces ferroptosis by sponging hsa-let-7b-5p which upregulates the expression of P53.
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
In total 4 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [5]
Target for Ferroptosis Suppressor
Responsed Disease Acute myeloid leukemia [ICD-11: 2A60]
Responsed Drug Perillaldehyde Investigative
Pathway Response Glutathione metabolism hsa00480
Cell Process Cell ferroptosis
In Vitro Model Jurkat cells T acute lymphoblastic leukemia Homo sapiens CVCL_0065
DLD-1 cells Colon adenocarcinoma Homo sapiens CVCL_0248
SH-SY5Y cells Neuroblastoma Homo sapiens CVCL_0019
HL-60 cells Adult acute myeloid leukemia Homo sapiens CVCL_0002
Response regulation We investigated and characterized its antileukemic potential in vitro, disclosing its ability to trigger ferroptosis. Specifically, perillaldehyde induced lipid peroxidation, decreased glutathione peroxidase 4 protein expression, and depleted intracellular glutathione on HL-60 promyelocytic leukemia cells.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [6]
Target for Ferroptosis Suppressor
Responsed Disease Acute myeloid leukemia [ICD-11: 2A60]
Responsed Drug APR-246 Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Glutathione metabolism hsa00480
Cell Process Cell ferroptosis
In Vitro Model HL-60 cells Adult acute myeloid leukemia Homo sapiens CVCL_0002
MOLM-14 cells Leukemia Homo sapiens CVCL_7916
SET-2 cells Acute megakaryoblastic leukemia Homo sapiens CVCL_2187
MV4-11 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0064
OCI-AML-2 cells Acute myeloid leukemia Homo sapiens CVCL_1619
OCI-AML3 cells Adult acute myeloid leukemia Homo sapiens CVCL_1844
K-562 cells Chronic myelogenous leukemia Homo sapiens CVCL_0004
THP-1 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0006
UT-7/Epo cells Acute megakaryoblastic leukemia Homo sapiens CVCL_5202
SKM-1 cells Acute myeloid leukemia Homo sapiens CVCL_0098
NB4 cells Acute promyelocytic leukemia Homo sapiens CVCL_0005
Kasumi-1 cells Acute myeloid leukemia Homo sapiens CVCL_0589
In Vivo Model
Xenograft tumors were generated by randomly injecting 1 x 106 MOLM14 shCTRL or shSLC7A11 cells into the tail veins of NOD/SCID IL-2 receptor g-chain-null mice (NSG) aged 6-9 weeks. Fourteen days after injection, doxycycline (200 mg/mL) and sucrose (1% weight:volume) were added to the drinking water of these animals. After 3 days, the mice were randomly treated with a daily intraperitoneal injection of APR-246 (100 mg/kg) or vehicle (phosphate-buffered saline [PBS]) for 4 days.

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Response regulation APR-246 is a promising new therapeutic agent that targets p53 mutated proteins in myelodysplastic syndromes and in acute myeloid leukemia (AML). The association of APR-246 with induction of ferroptosis (either by pharmacological compounds, or genetic inactivation of SLC7A11 or GPX4) had a synergistic effect on the promotion of cell death, both in vivo and ex vivo.
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target [7]
Target for Ferroptosis Suppressor
Responsed Disease Acute myeloid leukemia [ICD-11: 2A60]
Responsed Drug Sulforaphane Investigative
Pathway Response Glutathione metabolism hsa00480
Fatty acid metabolism hsa01212
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell proliferation
Cell apoptosis
In Vitro Model U-937 cells Adult acute monocytic leukemia Homo sapiens CVCL_0007
MV4-11 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0064
Response regulation Sulforaphane triggers different types of PCD in a concentration-dependent manner on the two tested acute myeloid leukemia cell lines. Deepening the molecular mechanisms on U-937 cells, we discovered that at lower concentrations, SFN induces apoptosis; at higher concentrations, SFN elicits ferroptosis, characterized by the depletion of intracellular GSH, the downregulation of GPX4 protein expression, and lipid peroxidation.
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target [8]
Target for Ferroptosis Suppressor
Responsed Disease Acute myeloid leukemia [ICD-11: 2A60]
Responsed Regulator Aldehyde dehydrogenase family 3 member A2 (ALDH3A2) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model HL-60 cells Adult acute myeloid leukemia Homo sapiens CVCL_0002
MOLM-14 cells Leukemia Homo sapiens CVCL_7916
Mono-Mac-6 cells Acute monocytic leukemia Homo sapiens CVCL_1426
NB4 cells Acute promyelocytic leukemia Homo sapiens CVCL_0005
NOMO-1 cells Acute monocytic leukemia Homo sapiens CVCL_1609
THP-1 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0006
In Vivo Model
Six- to 12-week-old Aldh-mut and Aldh-Ctrl mice were used to generate MLL-AF9 leukemia through retroviral transduction. This was transplanted into lethally irradiated (9 Gy) primary leukemic C57BL/6J mice and then into sublethally irradiated (4.5 Gy) secondary leukemic C57BL/6J mice. Forty-eight hours after injection into secondary recipients, these mice received 3 doses of polyinosinic-polycytidylic acid (GE Healthcare) on alternate days.

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Response regulation Aldh3a2 inhibition was synthetically lethal with glutathione peroxidase-4 (GPX4) inhibition; GPX4 inhibition is a known trigger of ferroptosis that by itself minimally affects acute myeloid leukemia cells. Inhibiting Aldh3a2 provides a therapeutic opportunity and a unique synthetic lethality to exploit the distinctive metabolic state of malignant cells.
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [9]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Acute myeloid leukemia [ICD-11: 2A60]
Responsed Drug All-trans retinoic acid derivative Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model NB4 cells Acute promyelocytic leukemia Homo sapiens CVCL_0005
HL-60 cells Adult acute myeloid leukemia Homo sapiens CVCL_0002
U-937 cells Adult acute monocytic leukemia Homo sapiens CVCL_0007
In Vivo Model
Six- to seven-week-old female NCG mice were obtained from the Nanjing model animal research institute (Nanjing, China). Mice were raised in individually ventilated cages of Anhui Medical University (Hefei, China). Then, an injection of NB4 cells (5 x 106/100 ul) suspended in chilled Matrigel and PBS (1:1) was given into the right flank of each mouse. For each experiment, the animals (n = 12) were randomly allocated into the two groups and treated with solvent or 10 mg/kg ATPR (intraperitoneal injection, once every other day) for 7 days.

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Response regulation ATPR, a novel all-trans retinoic acid (ATRA) derivative, has been extensively developed to show superior anticancer effect than ATRA in acute myeloid leukemia (AML). ATPR-induced ferroptosis was regulated by autophagy via iron homeostasis, especially Nrf2.
Heme oxygenase 1 (HMOX1)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [10]
Target for Ferroptosis Driver
Responsed Disease Acute myeloid leukemia [ICD-11: 2A60]
Responsed Drug Honokiol Investigative
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model THP-1 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0006
U-937 cells Adult acute monocytic leukemia Homo sapiens CVCL_0007
SKM-1 cells Acute myeloid leukemia Homo sapiens CVCL_0098
Response regulation Honokiol decreased the viability of the targeted Acute myeloid leukemia cells, induced their cell cycle arrest at G0/G1 phase, and inhibited their colony-formation capacity. Honokiol also triggers a noncanonical ferroptosis pathway in THP-1 and U-937 cells by upregulating the level of intracellular lipid peroxide and HMOX1 significantly. And HMOX1 was a critical target in honokiol-induced ferroptosis.
Ferritin heavy chain (FTH1)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Acute myeloid leukemia [ICD-11: 2A60]
Responsed Regulator Iron-sulfur cluster assembly enzyme ISCU (ISCU) Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
Cell proliferation
Cell cycle
In Vitro Model HL-60 cells Adult acute myeloid leukemia Homo sapiens CVCL_0002
KG1 cells Normal Mus musculus CVCL_UD72
THP-1 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0006
In Vivo Model
BALB/c Nude Mice (4 weeks old) were obtained from Shanghai Experimental Animal Center of the Chinese Academy of Sciences (Shanghai, China) and then subcutaneously injection with HL60 cells (1 x 107, suspended in 0.1 mL PBS). After tumors reached 100-200 mm3, the mice were randomly assigned to two groups. DHA was administered intraperitoneal injection once a day at 50 mg/kg body weight and the mice in normal control were received equal amounts of vehicle (10% DMSO in sterile corn oil). On the 28th day, mice were euthanized. The tumor volumes were measured every 4 days with a caliper.

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Response regulation Dihydroartemisinin (DHA) strongly inhibited the viability of acute myeloid leukemia (AML) cell lines and arrest cell cycle at G0/G1 phase. ISCU over-expression robustly alleviated the iron starvation response through regulating the expression of IRPs and downstream FTH. ISCU significantly attenuated DHA induced ferroptosis by regulating iron metabolism, rescuing the mitochondrial function and increasing the level of GSH.
Cystine/glutamate transporter (SLC7A11)
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [11]
Target for Ferroptosis Suppressor
Responsed Disease Childhood acute monocytic leukemia [ICD-11: 2A60]
Responsed Drug Indole-3-pyruvic acid Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model THP-1 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0006
MLL/AF4+ RS4 cells Adult B acute lymphoblastic leukemia Homo sapiens CVCL_0093
HEK-293T cells Normal Homo sapiens CVCL_0063
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
NIH3T3 cells Normal Mus musculus CVCL_0594
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
Response regulation Indole-3-pyruvate (I3P) suppresses ferroptosis by direct free radical scavenging and through the activation of an anti-oxidative gene expression program in Childhood acute monocytic leukemia. And I3P elevated the activation of compensatory gene expression as indicated by increased protein amounts of SLC7A11 and HO-1, two important target genes of anti-oxidative stress pathways.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [12]
Target for Ferroptosis Suppressor
Responsed Disease Acute myeloid leukemia [ICD-11: 2A60]
Responsed Regulator Lysine-specific demethylase 3B (KDM3B) Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
HEK293 cells Normal Homo sapiens CVCL_0045
THP-1 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0006
Response regulation Since KDM3B has been shown to associate with acute myeloid leukemia (AML). KDM3B protects cells from Erastininduced ferroptosis through transcriptional upregulation of SLC7A11 via interaction with ATF4.
References
Ref 1 PRMT1 inhibition promotes ferroptosis sensitivity via ACSL1 upregulation in acute myeloid leukemia. Mol Carcinog. 2023 Aug;62(8):1119-1135. doi: 10.1002/mc.23550. Epub 2023 May 5.
Ref 2 DHA inhibits proliferation and induces ferroptosis of leukemia cells through autophagy dependent degradation of ferritin. Free Radic Biol Med. 2019 Feb 1;131:356-369. doi: 10.1016/j.freeradbiomed.2018.12.011. Epub 2018 Dec 14.
Ref 3 Dihydroartemisinin-induced ferroptosis in acute myeloid leukemia: links to iron metabolism and metallothionein. Cell Death Discov. 2023 Mar 17;9(1):97. doi: 10.1038/s41420-023-01371-8.
Ref 4 Typhaneoside prevents acute myeloid leukemia (AML) through suppressing proliferation and inducing ferroptosis associated with autophagy. Biochem Biophys Res Commun. 2019 Sep 3;516(4):1265-1271. doi: 10.1016/j.bbrc.2019.06.070. Epub 2019 Jul 10.
Ref 5 Perillaldehyde is a new ferroptosis inducer with a relevant clinical potential for acute myeloid leukemia therapy. Biomed Pharmacother. 2022 Oct;154:113662. doi: 10.1016/j.biopha.2022.113662. Epub 2022 Sep 7.
Ref 6 APR-246 induces early cell death by ferroptosis in acute myeloid leukemia. Haematologica. 2022 Feb 1;107(2):403-416. doi: 10.3324/haematol.2020.259531.
Ref 7 Discovery of Sulforaphane as an Inducer of Ferroptosis in U-937 Leukemia Cells: Expanding Its Anticancer Potential. Cancers (Basel). 2021 Dec 24;14(1):76. doi: 10.3390/cancers14010076.
Ref 8 Aldehyde dehydrogenase 3a2 protects AML cells from oxidative death and the synthetic lethality of ferroptosis inducers. Blood. 2020 Sep 10;136(11):1303-1316. doi: 10.1182/blood.2019001808.
Ref 9 Targeting ferroptosis contributes to ATPR-induced AML differentiation via ROS-autophagy-lysosomal pathway. Gene. 2020 Sep 10;755:144889. doi: 10.1016/j.gene.2020.144889. Epub 2020 Jun 10.
Ref 10 Honokiol Induces Ferroptosis by Upregulating HMOX1 in Acute Myeloid Leukemia Cells. Front Pharmacol. 2022 May 11;13:897791. doi: 10.3389/fphar.2022.897791. eCollection 2022.
Ref 11 Anti-ferroptotic mechanism of IL4i1-mediated amino acid metabolism. Elife. 2021 Mar 1;10:e64806. doi: 10.7554/eLife.64806.
Ref 12 Histone demethylase KDM3B protects against ferroptosis by upregulating SLC7A11. FEBS Open Bio. 2020 Apr;10(4):637-643. doi: 10.1002/2211-5463.12823. Epub 2020 Mar 18.
Ref 13 A ferroptosis-related gene signature and immune infiltration patterns predict the overall survival in acute myeloid leukemia patients. Front Mol Biosci. 2022 Aug 15;9:959738. doi: 10.3389/fmolb.2022.959738. eCollection 2022.
Ref 14 CircKDM4C upregulates P53 by sponging hsa-let-7b-5p to induce ferroptosis in acute myeloid leukemia. Environ Toxicol. 2021 Jul;36(7):1288-1302. doi: 10.1002/tox.23126. Epub 2021 Mar 18.