Journal: Leukemia

Article Title: Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL

doi: 10.1038/s41375-019-0653-z

Figure Lengend Snippet: Impact of SKP2 depletion on normal lymphopoiesis. a Flow cytometry analysis of thymic subsets in Skp2 +/+ and Skp2 −/− mice. Percentage of DN, DP, CD4-SP, and CD8-SP cells within the whole thymus and of DN1-4 within the DN subpopulation; n = 6 ( Skp2 −/− ) and n = 9 ( Skp2 +/+ ) in three independent experiments. b Percentage of cells in S-phase measured by BrdU incorporation in indicated T-cell subsets in Skp2 +/+ and Skp2 −/− thymocytes; n = 4 ( Skp2 −/− ) and n = 7 ( Skp2 +/+ ) in two independent experiments. c Naive T-cells from Skp2 +/+ and Skp2 −/− mice stained with CFSE (10 µM) were activated with anti-CD3 (2 µg/mL) and anti-CD28 (0.5 µg/mL) for 2 days (left panel). On day 3, an equal number of cells were CFSE stained and further treated for 72 h with 5 ng/ml of IL-7 (right panel). Black and red or gray lines show CFSE dilution in the Skp2 +/+ and Skp2 −/− T-cells, respectively. Solid or dashed histograms show equal loading/Time 0 of the CFSE dye (representative experiment, n = 3). In bar graphs, results are shown as average ± SD

Article Snippet: The SKP2 inhibitor C1 [ ] and C25 [ ] (MedChemExpress), were used to inhibit SKP2 at concentrations from 0–80 μM.

Techniques: Flow Cytometry, BrdU Incorporation Assay, Staining

Journal: Leukemia

Article Title: Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL

doi: 10.1038/s41375-019-0653-z

Figure Lengend Snippet: Activation of Notch and IL-7 signaling pathways cooperate to heighten SKP2 expression. a Fold change for Skp2 mRNA expression measured by qRT-PCR in fresh population of total thymoctes harvested from Rbpj +/+ or Rbpj −/− mice (Day 0). Results are indicated as average ± SE; n = 6 ( Rbpj −/− ) and n = 9 ( Rbpj +/+ ) in two independent experiments. b Fold change for Skp2 , Deltex , and Hey1 mRNA expression measured by qRT-PCR in total thymocytes at 24 h of co-culture with OP9-Dll1 cells in the presence of DMSO or 5 µM GSI; each group n = 4. c Fold change for Skp2 mRNA expression measured by qRT-PCR in two independent experiments. Left panel: Rbpj +/+ or Rbpj −/− total thymocytes population at 4 days of co-cultured with OP9 or OP9-Dll1 cells in the presence of IL-7 (25 ng/ml); n = 3 ( Rbpj −/− ) and n = 4 ( Rbpj +/+ ). Right panel: total thymocytes at 24 h of co-culture with OP9 or OP9-Dll1 cells in the absence or presence of IL-7 (25 ng/ml); n = 3 (OP9 ) and n = 4 (OP9-Dll1). All results are expressed as average ± SD. * p < 0.05, ** p < 0.01, *** p < 0.005 by t -test or one-way ANOVA

Article Snippet: The SKP2 inhibitor C1 [ ] and C25 [ ] (MedChemExpress), were used to inhibit SKP2 at concentrations from 0–80 μM.

Techniques: Activation Assay, Expressing, Quantitative RT-PCR, Co-Culture Assay, Cell Culture

Journal: Leukemia

Article Title: Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL

doi: 10.1038/s41375-019-0653-z

Figure Lengend Snippet: SKP2 expression is upregulated in vivo in the Notch-induced T-ALL model. Lin − cells from C57Bl/6 mice (CD45.2) were transduced with MSCV-GFP (Vector) or MSCV-ICN1-GFP (ICN) constructs. 2.5 × 10 4 ICN/GFP + cells were transplanted into lethally irradiated BoyJ (CD45.1). Recipients were analyzed for: a Fold change for human Skp2 mRNA expression measured by qRT-PCR in the BM (left panel; n = 5) and Sp (right panel; n = 6 (vector) and n = 10(ICN)). b CHIP assay. DNA isolated from the thymus of mice transplanted with ICN-GFP + cells was immunoprecipitated with anti-Notch1 (N1) or anti-Jagged1 (irrelevant) antibodies Top panel: Scatter graph shows fold changes in SKP2 promoter enrichment measured by qRT-PCR (each group n = 3). Bottom panel: schematic representation of the Notch/RBPj binding sites within the mouse Skp2 promoter. All results are from two independent experiments. In scatter plots average is shown by a horizontal line.* p < 0.05, ** p < 0.01, *** p < 0.005 by t -test

Article Snippet: The SKP2 inhibitor C1 [ ] and C25 [ ] (MedChemExpress), were used to inhibit SKP2 at concentrations from 0–80 μM.

Techniques: Expressing, In Vivo, Transduction, Plasmid Preparation, Construct, Irradiation, Quantitative RT-PCR, Isolation, Immunoprecipitation, Binding Assay

Journal: Leukemia

Article Title: Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL

doi: 10.1038/s41375-019-0653-z

Figure Lengend Snippet: Loss of SKP2 attenuates Notch-induced leukemia. Lin − cells from Skp2 +/+ , Skp2 +/− , or Skp2 −/− (CD45.2) mice were transduced with MSCV-GFP (Vector), MSCV-ICN1-GFP (ICN), or MSCV-N1ΔEGFΔLNRΔP-GFP (N1ΔEGF) constructs. 2.5 × 10 4 GFP + cells were transplanted into lethally irradiated BoyJ (CD45.1) recipients (three independent experiments) and were analyzed for: a Percentage of DP T-cells in in gated CD45.2 + donor cells in PB. Skp2 +/+ Vector ( n = 6), Skp2 +/+ ICN ( n = 10), Skp2 +/− ICN ( n = 10) and Skp2 −/− ICN ( n = 6); (average ± SE). b Bar graph show BrdU incorporation in GFP + cells from Skp2 +/+ ICN ( n = 5) and Skp2 −/− ICN ( n = 3) in BM and spleen populations analyzed in recipients at week 8 from transplant. c Kaplan–Meier survival curve. Control cohorts include: Skp2 +/+ Vector group ( n = 10; green solid line) and Skp2 −/− nontransduced and Skp2 −/− Vector group ( n = 8; dark green dashed line); all these groups behaved identically. Experimental cohorts: in left panel include Skp2 +/+ ICN ( n = 19; blue line), Skp2 −/+ ICN ( n = 14; purple line) and Skp2 −/− ICN ( n = 14; red line); in right panel includes Skp2 +/+ N1ΔEGF ( n = 6; blue line) and for Skp2 −/− N1ΔEGF ( n = 6; red line). d Scheme representing the survival percentages of Skp2 −/− ICN ns (solid red) and Skp2 −/− ICN s (dashed red). Mice within Skp2 −/− ICN genotype were distributed in two groups based on their survival, here called Skp2 −/− ICN ns (no survivors; 71%) and Skp2 −/− ICN s (survivors; 29%). Recipients of all genotypes (in three independent experiments), were analyzed at full-blown disease or at 1 year from transplant. e Line graph in left panel represents counts of WBC in the PB of recipient mice at the time points indicated. Line graph in right panel represents percentage of GFP + cells gated on CD45.2 + cells in the PB of recipient mice at the time points indicated (average ± SE). Skp2 +/+ Vector ( n = 6), Skp2 +/+ ICN ( n = 10), Skp2 −/− ICN ns ( n = 6), and Skp2 −/− ICN s ( n = 3). Arrows indicates point of divergence between Skp2 −/− ICN s and Skp2 −/− ICN ns . All results are expressed as average ± SD unless otherwise indicated. * p < 0.05, ** p < 0.01, *** p < 0.005 by two-sample t -test, t -test or log-rank test

Article Snippet: The SKP2 inhibitor C1 [ ] and C25 [ ] (MedChemExpress), were used to inhibit SKP2 at concentrations from 0–80 μM.

Techniques: Transduction, Plasmid Preparation, Construct, Irradiation, BrdU Incorporation Assay, Control

Journal: Leukemia

Article Title: Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL

doi: 10.1038/s41375-019-0653-z

Figure Lengend Snippet: SKP2 blockade by small molecule inhibitors reduces proliferation of T-ALL in cell lines, primary cells, and in vivo in a xenograft model of T-ALL. Viability assays for the C1 inhibitor were performed at 96 h for cell lines and 48 h for primary cells. DMSO was used as vehicle control in all experiments. a Percentage viability of human T-ALL cell lines treated with increasing doses of the SKP2 inhibitor C1 (average ± SE). SupT1, HBP-ALL ( n = 4), and all other cell lines ( n = 6) in three independent experiments. b Percentage viability of primary T-ALL patient cells treated with increasing doses of the SKP2 inhibitor C1 (three patients samples, two independent experiment). c Top panel: percentage viability of TAIL7 cells treated with increasing doses of the SKP2 inhibitor C1 ( n = 6 in three independent experiments). Bottom panel: percentage of cells in S-phase measured by BrdU incorporation and percentage of apoptotic cells measured by Annexin V in TAIL7 cells treated for 48 h with 2.5 µM C1 or DMSO; n = 4. d Percentage of cells in S-phase measured by BrdU incorporation and percentage of apoptotic cells measured by Annexin V in TAIL7 cells treated for 48 h with 30 µM C25 or DMSO as vehicle control (average ± SD); n = 3. e Western blot (top) and densitometry analysis (bottom) of SKP2, p27 Kip1 , and β-Actin protein levels in TAIL7 cells treated with DMSO, 2.5 µM C1 and 30 µM C25 for 48 h; four independent experiments. f Immunofluorescence images show accumulation and localization of p27 kip1 (red) in the nucleus (blue) in TAIL7 cells following treatment with 30 µM of C25 or DMSO for 48 h (representative of three independent experiments). g Line graph shows average percentage of ICN-GFP + blasts in the PB of each recipient mouse at the time points indicated. End point is the last point indicated in the graph. h Kaplan–Meier survival curve. All experiments are shown as average ± SD unless otherwise indicated. ** p < 0.01, *** p < 0.005 by t -test. p = 0.009 by long rank test

Article Snippet: The SKP2 inhibitor C1 [ ] and C25 [ ] (MedChemExpress), were used to inhibit SKP2 at concentrations from 0–80 μM.

Techniques: In Vivo, Control, BrdU Incorporation Assay, Western Blot, Immunofluorescence

Journal: Leukemia

Article Title: Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL

doi: 10.1038/s41375-019-0653-z

Figure Lengend Snippet: A Notch/SKP2/IL-7 signature defines human T-ALL samples. a Expression of SKP2, NOTCH1, HES1, and IL-7r transcripts (CPM) across primary T-ALL, ETP-ALL, and B-ALL cases ( n = 17, 34, and 154, respectively). b Principal component analysis showing the distribution of primary T-ALL, B-ALL, and AML samples according to their whole transcriptome (left panel) or to the expression of 23 key genes involved in NOTCH and IL-7 signaling pathways (right panel)

Article Snippet: The SKP2 inhibitor C1 [ ] and C25 [ ] (MedChemExpress), were used to inhibit SKP2 at concentrations from 0–80 μM.

Techniques: Expressing

Journal: Pharmaceuticals

Article Title: Tyrphostin AG1024 Suppresses Coronaviral Replication by Downregulating JAK1 via an IR/IGF-1R Independent Proteolysis Mediated by Ndfip1/2_NEDD4-like E3 Ligase Itch

doi: 10.3390/ph15020241

Figure Lengend Snippet: NEDD4-like Itch E3 inhibition restored the AG1024 downregulated JAK1. ( A ) Neither the NEDD4 inhibitor heclin ( a ) nor the skp2 inhibitors SKPin C1 and CC220 ( b ) restored AG1024 downregulated JAK1, whereas the NEDD4 inhibitor heclin restored ouabain diminished JAK1 protein level. ( B ) Itch E3 inhibitors clomipramine and CPZ significantly restored the AG1024 downregulated JAK1. TGEV infected (MOI: 7) ST cells were treated with ouabain, AG1024, heclin, MLN4924, SKPin C1, CC220, clomipramine, or CPZ as indicated and harvested at 5 h.p.i. MLN4924, a NEDD8 inhibitor, served as a non-specific reference control, and the concentrations were used as reported . The concentrations of SKPin C1, CC220, clomipramine, or CPZ used herein were based on previous reports [ , , , , ]. The resulting lysates were subjected to western analyses. *, p < 0.05; **, p < 0.01. Results shown are averages ± SD from three independent experiments.

Article Snippet: DMSO (≧99.5%), human insulin (I2643, ≧98%, HPLC), ouabain (O3125, ≧95%, HPLC), and clomipramine hydrochloride (C7291, ≧98%, HPLC) were purchased from Sigma-Aldrich (St. Louis, MO, USA); MG132 (474790, ≧98%, HPLC) from Merck Millipore Calbiochem (Merck, La Jolla, CA, USA); AG1024 (S1234, ≧99.7%, HPLC), picropodophyllin (PPP, S7668, ≧99.5%, HPLC), MLN4924 (S7109, ≧99%, HPLC), chlorpromazine (CPZ, S5749, ≧97%, HPLC), Skp2 inhibitor C1 (SKPin C1, S8652, ≧99%, HPLC) and iberdomide (CC-220, S8760, ≧98%, HPLC) from Selleckchem (Houston, TX, USA); heclin (5433, ≧98%, HPLC) from Tocris Bioscience (Minneapolis, MN, USA); and human IGF-1 (CYT-216, ≧98%, SDS-PAGE) from ProSpec (Rehovot, Israel).

Techniques: Inhibition, Infection, Control, Western Blot

Journal: Leukemia

Article Title: Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL

doi: 10.1038/s41375-019-0653-z

Figure Lengend Snippet: Impact of SKP2 depletion on normal lymphopoiesis. a Flow cytometry analysis of thymic subsets in Skp2 +/+ and Skp2 −/− mice. Percentage of DN, DP, CD4-SP, and CD8-SP cells within the whole thymus and of DN1-4 within the DN subpopulation; n = 6 ( Skp2 −/− ) and n = 9 ( Skp2 +/+ ) in three independent experiments. b Percentage of cells in S-phase measured by BrdU incorporation in indicated T-cell subsets in Skp2 +/+ and Skp2 −/− thymocytes; n = 4 ( Skp2 −/− ) and n = 7 ( Skp2 +/+ ) in two independent experiments. c Naive T-cells from Skp2 +/+ and Skp2 −/− mice stained with CFSE (10 µM) were activated with anti-CD3 (2 µg/mL) and anti-CD28 (0.5 µg/mL) for 2 days (left panel). On day 3, an equal number of cells were CFSE stained and further treated for 72 h with 5 ng/ml of IL-7 (right panel). Black and red or gray lines show CFSE dilution in the Skp2 +/+ and Skp2 −/− T-cells, respectively. Solid or dashed histograms show equal loading/Time 0 of the CFSE dye (representative experiment, n = 3). In bar graphs, results are shown as average ± SD

Article Snippet: The SKP2 inhibitor C1 [ ] and C25 [ ] (MedChemExpress), were used to inhibit SKP2 at concentrations from 0–80 μM.

Techniques: Flow Cytometry, BrdU Incorporation Assay, Staining

Journal: Leukemia

Article Title: Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL

doi: 10.1038/s41375-019-0653-z

Figure Lengend Snippet: Activation of Notch and IL-7 signaling pathways cooperate to heighten SKP2 expression. a Fold change for Skp2 mRNA expression measured by qRT-PCR in fresh population of total thymoctes harvested from Rbpj +/+ or Rbpj −/− mice (Day 0). Results are indicated as average ± SE; n = 6 ( Rbpj −/− ) and n = 9 ( Rbpj +/+ ) in two independent experiments. b Fold change for Skp2 , Deltex , and Hey1 mRNA expression measured by qRT-PCR in total thymocytes at 24 h of co-culture with OP9-Dll1 cells in the presence of DMSO or 5 µM GSI; each group n = 4. c Fold change for Skp2 mRNA expression measured by qRT-PCR in two independent experiments. Left panel: Rbpj +/+ or Rbpj −/− total thymocytes population at 4 days of co-cultured with OP9 or OP9-Dll1 cells in the presence of IL-7 (25 ng/ml); n = 3 ( Rbpj −/− ) and n = 4 ( Rbpj +/+ ). Right panel: total thymocytes at 24 h of co-culture with OP9 or OP9-Dll1 cells in the absence or presence of IL-7 (25 ng/ml); n = 3 (OP9 ) and n = 4 (OP9-Dll1). All results are expressed as average ± SD. * p < 0.05, ** p < 0.01, *** p < 0.005 by t -test or one-way ANOVA

Article Snippet: The SKP2 inhibitor C1 [ ] and C25 [ ] (MedChemExpress), were used to inhibit SKP2 at concentrations from 0–80 μM.

Techniques: Activation Assay, Expressing, Quantitative RT-PCR, Co-Culture Assay, Cell Culture

Journal: Leukemia

Article Title: Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL

doi: 10.1038/s41375-019-0653-z

Figure Lengend Snippet: SKP2 expression is upregulated in vivo in the Notch-induced T-ALL model. Lin − cells from C57Bl/6 mice (CD45.2) were transduced with MSCV-GFP (Vector) or MSCV-ICN1-GFP (ICN) constructs. 2.5 × 10 4 ICN/GFP + cells were transplanted into lethally irradiated BoyJ (CD45.1). Recipients were analyzed for: a Fold change for human Skp2 mRNA expression measured by qRT-PCR in the BM (left panel; n = 5) and Sp (right panel; n = 6 (vector) and n = 10(ICN)). b CHIP assay. DNA isolated from the thymus of mice transplanted with ICN-GFP + cells was immunoprecipitated with anti-Notch1 (N1) or anti-Jagged1 (irrelevant) antibodies Top panel: Scatter graph shows fold changes in SKP2 promoter enrichment measured by qRT-PCR (each group n = 3). Bottom panel: schematic representation of the Notch/RBPj binding sites within the mouse Skp2 promoter. All results are from two independent experiments. In scatter plots average is shown by a horizontal line.* p < 0.05, ** p < 0.01, *** p < 0.005 by t -test

Article Snippet: The SKP2 inhibitor C1 [ ] and C25 [ ] (MedChemExpress), were used to inhibit SKP2 at concentrations from 0–80 μM.

Techniques: Expressing, In Vivo, Transduction, Plasmid Preparation, Construct, Irradiation, Quantitative RT-PCR, Isolation, Immunoprecipitation, Binding Assay

Journal: Leukemia

Article Title: Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL

doi: 10.1038/s41375-019-0653-z

Figure Lengend Snippet: Loss of SKP2 attenuates Notch-induced leukemia. Lin − cells from Skp2 +/+ , Skp2 +/− , or Skp2 −/− (CD45.2) mice were transduced with MSCV-GFP (Vector), MSCV-ICN1-GFP (ICN), or MSCV-N1ΔEGFΔLNRΔP-GFP (N1ΔEGF) constructs. 2.5 × 10 4 GFP + cells were transplanted into lethally irradiated BoyJ (CD45.1) recipients (three independent experiments) and were analyzed for: a Percentage of DP T-cells in in gated CD45.2 + donor cells in PB. Skp2 +/+ Vector ( n = 6), Skp2 +/+ ICN ( n = 10), Skp2 +/− ICN ( n = 10) and Skp2 −/− ICN ( n = 6); (average ± SE). b Bar graph show BrdU incorporation in GFP + cells from Skp2 +/+ ICN ( n = 5) and Skp2 −/− ICN ( n = 3) in BM and spleen populations analyzed in recipients at week 8 from transplant. c Kaplan–Meier survival curve. Control cohorts include: Skp2 +/+ Vector group ( n = 10; green solid line) and Skp2 −/− nontransduced and Skp2 −/− Vector group ( n = 8; dark green dashed line); all these groups behaved identically. Experimental cohorts: in left panel include Skp2 +/+ ICN ( n = 19; blue line), Skp2 −/+ ICN ( n = 14; purple line) and Skp2 −/− ICN ( n = 14; red line); in right panel includes Skp2 +/+ N1ΔEGF ( n = 6; blue line) and for Skp2 −/− N1ΔEGF ( n = 6; red line). d Scheme representing the survival percentages of Skp2 −/− ICN ns (solid red) and Skp2 −/− ICN s (dashed red). Mice within Skp2 −/− ICN genotype were distributed in two groups based on their survival, here called Skp2 −/− ICN ns (no survivors; 71%) and Skp2 −/− ICN s (survivors; 29%). Recipients of all genotypes (in three independent experiments), were analyzed at full-blown disease or at 1 year from transplant. e Line graph in left panel represents counts of WBC in the PB of recipient mice at the time points indicated. Line graph in right panel represents percentage of GFP + cells gated on CD45.2 + cells in the PB of recipient mice at the time points indicated (average ± SE). Skp2 +/+ Vector ( n = 6), Skp2 +/+ ICN ( n = 10), Skp2 −/− ICN ns ( n = 6), and Skp2 −/− ICN s ( n = 3). Arrows indicates point of divergence between Skp2 −/− ICN s and Skp2 −/− ICN ns . All results are expressed as average ± SD unless otherwise indicated. * p < 0.05, ** p < 0.01, *** p < 0.005 by two-sample t -test, t -test or log-rank test

Article Snippet: The SKP2 inhibitor C1 [ ] and C25 [ ] (MedChemExpress), were used to inhibit SKP2 at concentrations from 0–80 μM.

Techniques: Transduction, Plasmid Preparation, Construct, Irradiation, BrdU Incorporation Assay, Control

Journal: Leukemia

Article Title: Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL

doi: 10.1038/s41375-019-0653-z

Figure Lengend Snippet: SKP2 blockade by small molecule inhibitors reduces proliferation of T-ALL in cell lines, primary cells, and in vivo in a xenograft model of T-ALL. Viability assays for the C1 inhibitor were performed at 96 h for cell lines and 48 h for primary cells. DMSO was used as vehicle control in all experiments. a Percentage viability of human T-ALL cell lines treated with increasing doses of the SKP2 inhibitor C1 (average ± SE). SupT1, HBP-ALL ( n = 4), and all other cell lines ( n = 6) in three independent experiments. b Percentage viability of primary T-ALL patient cells treated with increasing doses of the SKP2 inhibitor C1 (three patients samples, two independent experiment). c Top panel: percentage viability of TAIL7 cells treated with increasing doses of the SKP2 inhibitor C1 ( n = 6 in three independent experiments). Bottom panel: percentage of cells in S-phase measured by BrdU incorporation and percentage of apoptotic cells measured by Annexin V in TAIL7 cells treated for 48 h with 2.5 µM C1 or DMSO; n = 4. d Percentage of cells in S-phase measured by BrdU incorporation and percentage of apoptotic cells measured by Annexin V in TAIL7 cells treated for 48 h with 30 µM C25 or DMSO as vehicle control (average ± SD); n = 3. e Western blot (top) and densitometry analysis (bottom) of SKP2, p27 Kip1 , and β-Actin protein levels in TAIL7 cells treated with DMSO, 2.5 µM C1 and 30 µM C25 for 48 h; four independent experiments. f Immunofluorescence images show accumulation and localization of p27 kip1 (red) in the nucleus (blue) in TAIL7 cells following treatment with 30 µM of C25 or DMSO for 48 h (representative of three independent experiments). g Line graph shows average percentage of ICN-GFP + blasts in the PB of each recipient mouse at the time points indicated. End point is the last point indicated in the graph. h Kaplan–Meier survival curve. All experiments are shown as average ± SD unless otherwise indicated. ** p < 0.01, *** p < 0.005 by t -test. p = 0.009 by long rank test

Article Snippet: The SKP2 inhibitor C1 [ ] and C25 [ ] (MedChemExpress), were used to inhibit SKP2 at concentrations from 0–80 μM.

Techniques: In Vivo, Control, BrdU Incorporation Assay, Western Blot, Immunofluorescence

Journal: Leukemia

Article Title: Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL

doi: 10.1038/s41375-019-0653-z

Figure Lengend Snippet: A Notch/SKP2/IL-7 signature defines human T-ALL samples. a Expression of SKP2, NOTCH1, HES1, and IL-7r transcripts (CPM) across primary T-ALL, ETP-ALL, and B-ALL cases ( n = 17, 34, and 154, respectively). b Principal component analysis showing the distribution of primary T-ALL, B-ALL, and AML samples according to their whole transcriptome (left panel) or to the expression of 23 key genes involved in NOTCH and IL-7 signaling pathways (right panel)

Article Snippet: The SKP2 inhibitor C1 [ ] and C25 [ ] (MedChemExpress), were used to inhibit SKP2 at concentrations from 0–80 μM.

Techniques: Expressing