Ferroptosis-centered Disease Response Information

General Information of the Disease (ID: DIS00017)
Name
Myeloid leukaemia
ICD
ICD-11: 2B33
Full List of Target(s) of This Ferroptosis-centered Disease
Cystine/glutamate transporter (SLC7A11)
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Myeloid leukaemia [ICD-11: 2B33]
Responsed Drug Vincristine Investigative
 Drug Info 
Responsed Regulator LINC00618 (IncRNA) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
In Vitro Model HL-60 cells Adult acute myeloid leukemia Homo sapiens CVCL_0002
K-562 cells Chronic myelogenous leukemia Homo sapiens CVCL_0004
Response regulation LINC00618, is reduced in human leukemia and strongly increased by vincristine (VCR) treatment. Furthermore, LINC00618 promotes apoptosis by increasing the levels of BCL2-Associated X (BAX) and cleavage of caspase-3. LINC00618 also accelerates ferroptosis by increasing the levels of lipid reactive oxygen species (ROS) and iron, two surrogate markers of ferroptosis, and decreasing the expression of solute carrier family 7 member 11 (SLC7A11).
Transferrin receptor protein 1 (TFRC)
 Target Info 
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/Driver
Responsed Disease Myeloid leukaemia [ICD-11: 2B33]
Responsed Regulator High mobility group protein B1 (HMGB1) Driver
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Apoptosis hsa04210
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell apoptosis
Cell autophagy
In Vitro Model HL-60 cells Adult acute myeloid leukemia Homo sapiens CVCL_0002
NB4 cells Acute promyelocytic leukemia Homo sapiens CVCL_0005
KG-1 cells Adult acute myeloid leukemia Homo sapiens CVCL_0374
U-937 cells Adult acute monocytic leukemia Homo sapiens CVCL_0007
THP-1 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0006
In Vivo Model
Seven- to eight-week male NOD/SCID (non-obese diabetic/severe combined immunodeficient) mice that weighed about 20 g were purchased from Xiangya Medical College Animal Laboratory (Changsha, China). Indicated HL-60/NRASQ61L cells were subcutaneously injected into the dorsal flanks right of the midline in NOD/SCID mice (weight, approximately 20 g). At day seven, mice were intraperitoneal injected with erastin (20 mg/kg i.v., three times a week) for two weeks. Erastin was dissolved in the vehicle (2% DMSO and 98% PBS) and prepared by Ultrasonic Cleaner (Fisher Scientific, Hampton, NH). A final volume of 300 uL of erastin was applied via intraperitoneal injection.

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Response regulation HMGB1 could be a potential drug target for therapeutic interventions in leukemia.Importantly, these data were further supported by our in vivo experiment, in which xenografts formed by HMGB1 knockdown HL-60/NRASQ61L cells had lower PTGS2 and TfR1 expression than that in control mice.
Prostaglandin G/H synthase 2 (PTGS2)
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Marker
Responsed Disease Myeloid leukaemia [ICD-11: 2B33]
Responsed Regulator High mobility group protein B1 (HMGB1) Driver
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Apoptosis hsa04210
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell apoptosis
Cell autophagy
In Vitro Model HL-60 cells Adult acute myeloid leukemia Homo sapiens CVCL_0002
NB4 cells Acute promyelocytic leukemia Homo sapiens CVCL_0005
KG-1 cells Adult acute myeloid leukemia Homo sapiens CVCL_0374
U-937 cells Adult acute monocytic leukemia Homo sapiens CVCL_0007
THP-1 cells Childhood acute monocytic leukemia Homo sapiens CVCL_0006
In Vivo Model
Seven- to eight-week male NOD/SCID (non-obese diabetic/severe combined immunodeficient) mice that weighed about 20 g were purchased from Xiangya Medical College Animal Laboratory (Changsha, China). Indicated HL-60/NRASQ61L cells were subcutaneously injected into the dorsal flanks right of the midline in NOD/SCID mice (weight, approximately 20 g). At day seven, mice were intraperitoneal injected with erastin (20 mg/kg i.v., three times a week) for two weeks. Erastin was dissolved in the vehicle (2% DMSO and 98% PBS) and prepared by Ultrasonic Cleaner (Fisher Scientific, Hampton, NH). A final volume of 300 uL of erastin was applied via intraperitoneal injection.

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Response regulation HMGB1 could be a potential drug target for therapeutic interventions in leukemia.Importantly, these data were further supported by our in vivo experiment, in which xenografts formed by HMGB1 knockdown HL-60/NRASQ61L cells had lower PTGS2 and TfR1 expression than that in control mice.
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
 Target Info 
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [3]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Myeloid leukaemia [ICD-11: 2B33]
Responsed Drug Triptolide Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model K-562 cells Chronic myelogenous leukemia Homo sapiens CVCL_0004
HL-60 cells Adult acute myeloid leukemia Homo sapiens CVCL_0002
HEK-293T cells Normal Homo sapiens CVCL_0063
Response regulation Triptolide inhibited Nrf2 expression and induced leukemia cell ferroptosis, as evidenced by increased ROS levels and lipid oxidation as well as decreased glutathione peroxidase 4 expression. Therefore, it is plausible that triptolide can promote leukemia cell sensitivity to DOX via downregulation of Nrf2 expression.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [4]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Acute lymphoblastic leukemia [ICD-11: 2B33]
Responsed Regulator Progestin and adipoQ receptor family member 3 (PAQR3) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Ubiquitin mediated proteolysis hsa04120
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model MOLT-3 cells T-lymphoblastic leukemia Homo sapiens CVCL_0624
MOLT4 cells Adult T acute lymphoblastic leukemia Homo sapiens CVCL_0013
CEM/C1 cells T acute lymphoblastic leukemia Homo sapiens CVCL_3496
Jurkat cells T acute lymphoblastic leukemia Homo sapiens CVCL_0065
Response regulation PAQR3 inhibited proliferation and aggravated ferroptosis in acute lymphoblastic leukemia through modulation Nrf2 stability. This study suggested that PAQR3 may serve as an effective biological marker for ALL treatment.
Unspecific Target
In total 5 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [5]
Responsed Disease Myeloid leukaemia [ICD-11: 2B33]
Responsed Drug Soyauxinium chloride Investigative
 Drug Info 
Pathway Response Apoptosis hsa04210
Ferroptosis hsa04216
Necroptosis hsa04217
Cell Process Cell ferroptosis
Cell apoptosis
Cell necroptosis
In Vitro Model CCRF-CEM cells T acute lymphoblastic leukemia Homo sapiens CVCL_0207
Response regulation The prominent cytotoxic potential of soyauxinium chloride (SCHL) on a panel of 18 human and animal cancer cell lines, including MDR phenotypes. This investigated indoloquinazoline alkaloid induced apoptosis in leukemia CCRF-CEM cells via caspases activation, MMP alteration and increase of ROS production, and caused ferroptosis and necroptosis.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [6]
Responsed Disease Myeloid leukaemia [ICD-11: 2B33]
Responsed Drug T. vulgaris and A. lappa Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell autophagy
Cell proliferation
In Vitro Model CCRF-CEM cells T acute lymphoblastic leukemia Homo sapiens CVCL_0207
NCI-H929 cells Plasma cell myeloma Homo sapiens CVCL_1600
Response regulation T. vulgaris and A. lappa could be considered as potential herbal drug candidates, which arrest leukemia cancer cell proliferation by induction of apoptosis, autophagic, and ferroptosis.
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target [7]
Responsed Disease Acute lymphoblastic leukemia [ICD-11: 2B33]
Responsed Regulator Circ_0000745 (circRNA) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Gluconeogenesis hsa00010
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell proliferation
Cell apoptosis
In Vitro Model Kasumi-1 cells Acute myeloid leukemia Homo sapiens CVCL_0589
KG-1 cells Adult acute myeloid leukemia Homo sapiens CVCL_0374
Response regulation Circ_0000745 promoted cell cycle progression and glycolytic metabolism and inhibited the apoptosis and ferroptosis of acute lymphoblastic leukemia cells by regulating miR-494-3p/NET1 axis. Circ_0000745/miR-494-3p/NET1 axis may provide novel potential targets for the diagnosis and treatment of acute lymphoblastic leukemia (ALL).
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target [7]
Responsed Disease Acute lymphoblastic leukemia [ICD-11: 2B33]
Responsed Regulator hsa-miR-494-3p (miRNA) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Gluconeogenesis hsa00010
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell proliferation
Cell apoptosis
In Vitro Model Kasumi-1 cells Acute myeloid leukemia Homo sapiens CVCL_0589
KG-1 cells Adult acute myeloid leukemia Homo sapiens CVCL_0374
Response regulation Circ_0000745 promoted cell cycle progression and glycolytic metabolism and inhibited the apoptosis and ferroptosis of acute lymphoblastic leukemia cells by regulating miR-494-3p/NET1 axis. Circ_0000745/ miR-494-3p/NET1 axis may provide novel potential targets for the diagnosis and treatment of acute lymphoblastic leukemia (ALL).
Experiment 5 Reporting the Ferroptosis-centered Disease Response by This Target [7]
Responsed Disease Acute lymphoblastic leukemia [ICD-11: 2B33]
Responsed Regulator Neuroepithelial cell-transforming gene 1 protein (NET1) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Gluconeogenesis hsa00010
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell proliferation
Cell apoptosis
In Vitro Model Kasumi-1 cells Acute myeloid leukemia Homo sapiens CVCL_0589
KG-1 cells Adult acute myeloid leukemia Homo sapiens CVCL_0374
Response regulation Circ_0000745 promoted cell cycle progression and glycolytic metabolism and inhibited the apoptosis and ferroptosis of acute lymphoblastic leukemia cells by regulating miR-494-3p/ NET1 axis. Circ_0000745/miR-494-3p/ NET1 axis may provide novel potential targets for the diagnosis and treatment of acute lymphoblastic leukemia (ALL).
References
Ref 1 A Nuclear Long Non-Coding RNA LINC00618 Accelerates Ferroptosis in a Manner Dependent upon Apoptosis. Mol Ther. 2021 Jan 6;29(1):263-274. doi: 10.1016/j.ymthe.2020.09.024. Epub 2020 Sep 20.
Ref 2 HMGB1 regulates erastin-induced ferroptosis via RAS-JNK/p38 signaling in HL-60/NRAS(Q61L) cells. Am J Cancer Res. 2019 Apr 1;9(4):730-739. eCollection 2019.
Ref 3 Triptolide promotes ferroptosis by suppressing Nrf2 to overcome leukemia cell resistance to doxorubicin. Mol Med Rep. 2023 Jan;27(1):17. doi: 10.3892/mmr.2022.12904. Epub 2022 Dec 1.
Ref 4 PAQR3 inhibits proliferation and aggravates ferroptosis in acute lymphoblastic leukemia through modulation Nrf2 stability. Immun Inflamm Dis. 2021 Sep;9(3):827-839. doi: 10.1002/iid3.437. Epub 2021 May 6.
Ref 5 The alkaloid, soyauxinium chloride, displays remarkable cytotoxic effects towards a panel of cancer cells, inducing apoptosis, ferroptosis and necroptosis. Chem Biol Interact. 2021 Jan 5;333:109334. doi: 10.1016/j.cbi.2020.109334. Epub 2020 Nov 24.
Ref 6 Induction of Apoptosis, Autophagy and Ferroptosis by Thymus vulgaris and Arctium lappa Extract in Leukemia and Multiple Myeloma Cell Lines. Molecules. 2020 Oct 29;25(21):5016. doi: 10.3390/molecules25215016.
Ref 7 Circ_0000745 promotes acute lymphoblastic leukemia progression through mediating miR-494-3p/NET1 axis. Hematology. 2022 Dec;27(1):11-22. doi: 10.1080/16078454.2021.2008590.