Journal: Nature Communications

Article Title: TET1 as a master regulator controlling GPX4-dependent and -independent ferroptosis surveillance in acute myeloid leukemia

doi: 10.1038/s41467-026-68509-x

Figure Lengend Snippet: a Comparison of gene expression patterns detected with RNA-seq in Kasumi-1 and MV4;11 cells. RNA-seq data were analyzed using FPKM values. Differential gene expression analysis was performed by edgeR between Kasumi-1 and MV4;11 cell lines, with significantly differentially expressed genes identified using the following cutoff criteria: absolute log2(fold change) ≥ 1 and P -value ≤ 0.05. Shown are genes expressed at a significantly higher level (red) or lower level (blue) in Kasumi-1 cells than in MV4;11 cells. b The top 10 genes of the chromatin_assembly_or_disassembly gene set expressed at higher level in Kasumi-1 than in MV4;11. c Correlation between TET1 expression level and cellular response to RSL3. Left panel: Curves of relative cell viability (RSL3-treated versus control) and basal expression level of TET1 in a 33-sample cohort, including 24 cancer cell lines and 9 primary AML samples. Curves were obtained with Gaussian fitting. TET1 expression levels were detected by Q-PCR and were normalized to TET1 basal level of Daudi cells. Right panel: The Pearson correlation analysis between the detected cell viability and lg-transformed TET1 gene expression levels. n = 3 biologically replicates. d TET1 knockdown increases sensitivity of THP1 cells to RSL3. Cells transfected with shNC or sh TET1 lentivirus were treated with RSL3 at indicated doses for 48 h. Relative cell viability is shown. n = 3 biologically replicates. Lipid peroxidation level in MA9 ( e ) or AE9a ( f )-AML cells of wild-type or Tet1 −/− mice treated with DMSO, 500 nM RSL3 or 500 nM RSL3 + 5 μM Fer-1 for 24 h. For e panels: n = 4 independent experiments for WT+ Ctrl and WT + RSL3 group; n = 3 independent experiments for WT + RSL3+ Fer-1, Tet1 −/− + Ctrl, Tet1 −/− + RSL3, and Tet1 −/− + RSL3+ Fer-1 group. For f panels: n = 3 independent experiments for all groups. Data are presented as mean ± SEM; * P < 0.05, ** P < 0.01, *** P < 0.001; Statistical significance was determined by two-way ANOVA with Tukey’s multiple comparisons test ( d ) or one-way ANOVA with Tukey’s multiple comparisons test ( e , f ). Exact P values and source data are provided as a Source Data file.

Article Snippet: THP1 (TIB-202), U937 (CRL-1593.2), and MV4;11 (CRL-9591) cells were obtained from America Type Culture Collection (ATCC) and cultured in RPMI-1640 medium (Gibco, Grand Island, NY, USA), supplemented with 10% FBS (Vistech) and penicillin-streptomycin.

Techniques: Comparison, Gene Expression, RNA Sequencing, Expressing, Control, Transformation Assay, Knockdown, Transfection

Journal: Nature Communications

Article Title: TET1 as a master regulator controlling GPX4-dependent and -independent ferroptosis surveillance in acute myeloid leukemia

doi: 10.1038/s41467-026-68509-x

Figure Lengend Snippet: Relative cell viability of GPX4 knockout MV4;11 ( a , n = 6 independent experiments) or Kasumi-1 ( b , n = 3 independent experiments for Ctrl group; n = 6 independent experiments for GPX4 OE group) cells with or without overexpression of GPX4 . Cells were cultured in the presence of 100 μM Trolox, and ferroptosis was induced by removing Trolox for 24 h. Relative cell viability of GPX4 knockout MV4;11 ( c , n = 6 independent experiments) or Kasumi-1 ( d , n = 3 independent experiments for Ctrl group; n = 6 independent experiments for TET1 and TET1 -HxD group) cells ectopically overexpressing TET1 or TET1 -HxD. Cells were cultured in the presence of 100 μM Trolox, and ferroptosis was induced by removal of Trolox for 24 h. Results of lipid peroxidation analysis in GPX4 knockout MV4;11 ( e ) or Kasumi-1 ( f ) cells with control, TET1, or TET1 -HxD overexpression. Cells were treated with 100 μM Trolox or DMSO for 24 h. Statistical results are shown (right panels, n = 3 independent experiments). The impacts of TET1 overexpression on lipid peroxidation level in GSTP1 , DHODH , FSP1 , GCH1 ( g ) knockout THP1 cells in the presence of RSL3 ( h ) or Erastin ( i ) for 24 h. n = 3 biologically replicates. Data are presented as mean ± SEM; * P < 0.05, ** P < 0.01, *** P < 0.001; Statistical significance was determined by unpaired two-tailed t -test ( a – d ) or one-way ANOVA with Tukey’s multiple comparisons test ( e , f and h , i ). Exact P values and source data are provided as a file.

Article Snippet: THP1 (TIB-202), U937 (CRL-1593.2), and MV4;11 (CRL-9591) cells were obtained from America Type Culture Collection (ATCC) and cultured in RPMI-1640 medium (Gibco, Grand Island, NY, USA), supplemented with 10% FBS (Vistech) and penicillin-streptomycin.

Techniques: Knock-Out, Over Expression, Cell Culture, Control, Two Tailed Test

Journal: Nature Communications

Article Title: TET1 as a master regulator controlling GPX4-dependent and -independent ferroptosis surveillance in acute myeloid leukemia

doi: 10.1038/s41467-026-68509-x

Figure Lengend Snippet: a Association between TET1 and the NFKB2 gene locus. Upper panel: Predicted TET1 binding site at the promoter region of NFKB2 . Lower panel: ChIP-Q-PCR results showing enrichment of TET1 at the NFKB2 promoter region in Kasumi-1 cells, which could be suppressed by TET1 knockdown. Cells were transfected with shNC or sh TET1 lentivirus. b Reporter analysis of NFKB2 transcription activity. The pGL3- NFKB2 promoter was co-transfected with shNC or sh TET1 , and luciferase reporter assay was performed. Expression levels of NFKB2 and GCH1 in MV4;11 cells transfected with shNC, sh NFKB2 −1, sh NFKB2 −2 ( c ) or pLJM1, NFKB2 ( d ) were detected through Q-PCR. e Reporter analysis of GCH1 transcription activity. The pGL3- GCH1 promoter was co-transfected with shNC, sh NFKB2 −1, or sh NFKB2 −2, and luciferase reporter assay was performed. f Expression levels of TET1 and GCH1 in TET1 knockdown or control MV4;11 cells were detected with Q-PCR. g Expression levels of TET1 and GCH1 in TET1 / TET1 -HxD overexpressing or control MV4;11 cells were detected with Q-PCR. h The impacts of GCH1 overexpression on cell viability in THP1 cells with TET1 knockdown under the conditions of RSL3 treatment for 48 h. Shown are the RSL3 dose curves (left panel) and the relative viability of cells treated with DMSO or 100 nM RSL3 (right panel). i Lipid ROS levels of THP1 cells co-transfected with pLJM1 or GCH1 and shNC or sh TET1 . Cells were treated with DMSO or 500 nM RSL3 for 24 h. Statistical results are shown (right panel). Relative cell viability of MV4;11 ( j ) and Kasumi-1 ( k ) cells after concurrently treated with DMSO, 100 nM RSL3, or 30 μM Bobcat339 for 48 h in the presence of DAHP at indicated doses. l Schematic depiction of the TET1 mediated ferroptosis surveillance system, i.e., the TET1/GCL axis and the TET1/GCH1 axis. Data are presented as mean ± SEM; n = 3 biologically independent replicates in ( a – k ); * P < 0.05, ** P < 0.01, *** P < 0.001; Statistical significance was determined by unpaired two-tailed t -test ( a – g ) or two-way ANOVA with Tukey’s multiple comparisons test ( h – k ). Exact P values and source data are provided as a file.

Article Snippet: THP1 (TIB-202), U937 (CRL-1593.2), and MV4;11 (CRL-9591) cells were obtained from America Type Culture Collection (ATCC) and cultured in RPMI-1640 medium (Gibco, Grand Island, NY, USA), supplemented with 10% FBS (Vistech) and penicillin-streptomycin.

Techniques: Binding Assay, Knockdown, Transfection, Activity Assay, Luciferase, Reporter Assay, Expressing, Control, Over Expression, Two Tailed Test

Journal: bioRxiv

Article Title: The sensitivity of acute myeloid leukemia to CDK8/19 inhibitors is determined by their metabolic profile

doi: 10.64898/2025.12.14.694205

Figure Lengend Snippet: AML cell sensitivity to CDK8/19i correlates with their metabolic properties. A. AML cell lines and their sensitivity to CCNC KO (CRISPR_CCNC (DepMap Public 25Q3+Score, Chronos)) and siRNA CCNC (siRNA_CCNC, (Achilles+DRIVE+Marcotte, DEMETER2)) as determined by DepMap or CDK8/19i as determined by minIC50 from published data. B . Distribution ridgeplots of CDK8/19i sensitive and resistant AML cells based on their average sensitivity to gene KO (DepMap, Chronos) in the groups determined using the Hallmark database. Data transformed using z-scaling. Groups of KO in which the greatest differences between groups of cells are expected are marked in green. C . Heatmap of genes whose KO directly correlates with AML sensitivity to CDK8/19i. Data was obtained from the DepMap (Public 25Q3+Score, Chronos) using Spearman correlation. Data were transformed using z-scaling. E . Distribution ridgeplots of CDK8/19i sensitive and resistant AML cells based on their metabolic indices (genes obtained from DepMap Expression Public 25Q3 database). The indices with the greatest differences between CDK8/19i sensitive and resistant AML cells are presented. G . A schematic diagram summarizing the major cellular processes that may be involved in the sensitivity of AML cells to CDK8/19i.

Article Snippet: Human AML cell lines MV4;11, KG-1 (Russian Collection of Cell Cultures, Saint-Petersburg, Russia), THP-1 (TIB-202 TM, ATCC), Kasumi-1 (the cells were provided by the Department of Genetics, Faculty of Biology, Belarusian State University) were propagated in RPMI-1640 (PanEco, Moscow, Russia) with 10% fetal bovine serum (Biosera, Cholet, France), 2 mM L-glutamine, 100 U/mL penicillin and 100 μg/mL streptomycin (PanEco) at 37°C and 5% CO2 in humidified atmosphere.

Techniques: CRISPR, Transformation Assay, Expressing