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Table 1 Nrf2 in leukemia

From: The molecular biology and therapeutic potential of Nrf2 in leukemia

Type of leukemia Type of study Cell line Study results Refs
CML In vitro K-562 and KU-812 Nrf2 gene targets such as HO-1 and NQO1 increased imatinib resistance and decreased apoptosis in CML [176]
CML In vitro K562/G01 When Nrf2 expression was inhibited by siRNA, reactive oxygen species (ROS) and the rate of apoptosis in response to imatinib increased, and cell proliferation decreased [177]
CML In vitro HL60/A(AML)
and K562 /G(CML)
Using Triptolide, a natural inhibitor of Nrf2, along with other drugs such as doxorubicin and imatinib, reduced HIF-1a, Nrf2, and drug resistance [178]
CML In vitro and in vivo K562/A02 and NOD/SCID mice Wogonin, an Nrf2 inhibitor, reduced Adriamycin resistance by inhibiting the Stat3/NF-κB—signaling [179, 180]
CML In vitro K562 Chaetominine disrupted the PI3K/Akt/Nrf2 signaling pathway, inhibited the MRP1-mediated drug efflux pump, induced Bax apoptotic protein, and inhibited anti-apoptotic proteins [181]
AML In vitro Blood samples from 15 AML patients (PBMC) Malignant AML stem cells increased NF-κB expression, responsible for high Nrf2 expression [144, 186]
AML In vitro THP-1, HL60, U937, and AML 193 In cells resistant to TNF-induced cell death, the Nrf2 pathway is activated [187]
AML In vitro 17 patients with AML and THP-1, HL60, and U937 1) Simultaneous inhibition of HO-1 and NF-κB might be fluent in increasing apoptosis
2) high expression of Nrf2 as a result of NF-κB expression
[91]
AML In vitro and in vivo THP-1, HL-60, U937, and CAMs of chicken eggs 4f drug-based therapy induces programmed cell death (dependent on mitochondria) by decreasing the level of Nrf2 protein and increasing caspase-3, cleaved poly (ADP-ribose) protein levels, a pro-apoptotic protein. Also, tumor growth was inhibited by 4f in a chick embryo model [188]
AML In vitro THP-1 and U937 Several Nrf2 inhibitors were identified, including ATRA, brusatol, and luteolin, which sensitized cells to arsenic trioxide (As2O3), etoposide, and doxorubicin [189]
AML In vitro HL60, Molm13, THP-1, and U937 Nrf2 inhibitor, Cytarabine, and Daunorubicin decreased drug resistance in AML [190]
AML In vitro KG1 Leukemia stem cells are resistant to apoptosis by activating the PERK/Nrf2 signaling pathway [191]
AML In vitro and in vivo KG1α, Kasumi-1 and NOD/SCID mice Disulfiram/copper, which had an inhibitory effect on NF-κB and Nrf2, killed the malignant stem cells in AML [192]
AML In vitro ALL (REH, MOLT4)
AML (MOLM-14)
Inhibition of MAPK/ERK and PI3K/AKT pathways reduced the expression of Nrf2, which was associated with downregulation of target genes, upregulation of ROS, and increased apoptosis [193]
AML In vitro U937
HL60
Nrf2 activators in AML cell line U937 prevented the toxicity of calcium (dimethyl fumarate (DMF), tert-butyl hydroquinone, or carnosic acid [194, 195]
AML In vitro U937, MOLM-13, HL-60, THP1, KG1a Combination therapy with cytarabine (AraC), DHA, and EPA in AML cell lines increased cell cytotoxicity [196]
APL In vitro PR9 (U937 cell line with zinc inducible PML/RARa expression) 1) Nrf2 expression in APL is lower than in AML because some inhibitory mechanisms hinder Nrf2 transcription activity
2) suppressing Nrf2 activity in APL made cells sensitive to treatment with high doses of ascorbate
[199]
APL In vitro NB4 NF-κB increased Nrf2 expression and leukemia progression [200]
CLL In vitro Blood samples (PBMC) The PBMC of patients with CLL had higher levels of Nrf2 than normal blood samples [203]
CLL In vitro Blood samples (PBMC) Increased ROR1 expression in CLL cells increases APRIL and BAFF-R expression, leading to the recruitment and accumulation of the p62 protein, which triggers several separate signaling pathways such as Nrf2 [204]
ALL In silico The Nrf2 inhibitory pathway and activation of this factor are disrupted in patients with ALL [205]
ALL In vitro REH, MOLT-4 Inhibition of MAPK/ERK and PI3K/AKT pathways reduced Nrf2/NF-κΒ and drug resistance
The combination of MAPK/ERK pathway inhibitors plus topoisomerase II inhibitor treatment synergistically increased the production of ROS and caused apoptosis in leukemic cells
[193, 207, 208]