mv4 11  (ATCC)

Journal: bioRxiv

Article Title: Combined Menin and XPO1 inhibition drive synergistic antileukemic activity in KMT2A r and NPM1 -m AML

doi: 10.64898/2026.03.10.710924

Figure Lengend Snippet: (A) Network topology map generated with Slorth ( www.slorth.biochem.sussex ) illustrating direct and indirect molecular interactions between MEN1 and XPO1. (B) IC 50 values of ziftomenib and selinexor in different KMT2A -r and NPM1 -m AML cell lines. (C-F) Ziftomenib and selinexor combination treatment in MV4;11 and MOLM13 KMT2A -r and IMS-M2 and OCI-AML3 NPM1 -m AML cell lines. (G-H) Normalized isobolograms for MV4;11 and MOLM13 KMT2A -r and IMS-M2 and OCI-AML3 NPM1 -m AML cell lines. Isobolograms were generated using Calcusyn 2.1 software. (I-J) Apoptotic cell deaths in MV4;11 and OCI-AML3 cells after ziftomenib, selinexor and combination treatments. Apoptotic cells were determined using annexin V-propidium iodide (PI) flow cytometric assay. DMSO or drug treatments were performed for 48-72 hours. Representative flow cytometric images are shown in the right panel. ***, p < 0.001.

Article Snippet: MV4;11 and MOLM13 cell lines were purchased from the American Type Culture Collection (ATCC, Manassas, VA, USA).

Techniques: Generated, Software, Flow Cytometry

Journal: bioRxiv

Article Title: Combined Menin and XPO1 inhibition drive synergistic antileukemic activity in KMT2A r and NPM1 -m AML

doi: 10.64898/2026.03.10.710924

Figure Lengend Snippet: (A&B) Quantitative expression of menin downstream targets in MV4;11 and OCI-AML3 cell lines as determined by real-time qPCR after 24 hours of treatment with ziftomenib (50 nM), selinexor (100 nM), or combination. (C&D) Expression of menin and its downstream target proteins, including HOXA9, MEIS1, when treated for 72 hours with either DMSO or 36 nM ziftomenib and 55 nM selinexor in MV4;11 and OCI-AML3 cells. (E) Global expression of mRNAs in the indicated treatment groups. (F) Affected gene ontology (GO) terms from GO analysis. (G) Circular heatmap of curated menin/KMT2A target gene expression across treatment conditions displays a curated set of bona fide menin/KMT2A/menin inhibitor-responsive genes identified from RNA sequencing. Expression patterns of these genes are shown across control, ziftomenib monotherapy, selinexor monotherapy, and ziftomenib-selinexor combination treatment groups in MV4;11 cells. Both upregulated and downregulated transcripts are highlighted, demonstrating the selective transcriptional modulation of menin/KMT2A target programs and the enhanced impact of combination therapy. (H) Differential expression of biologically relevant genes defined by heavy MLL/menin-bound loci and impact of different treatments on those genes in MV4;11 treated cells. Concentric rings 1 to 4 represent expression changes across four conditions (inner to outer: Control, Ziftomenib, Selinexor, and Combination), with color intensity reflecting log fold change (range −1.5 to +1.5).

Article Snippet: MV4;11 and MOLM13 cell lines were purchased from the American Type Culture Collection (ATCC, Manassas, VA, USA).

Techniques: Expressing, Targeted Gene Expression, RNA Sequencing, Control, Quantitative Proteomics

Journal: bioRxiv

Article Title: Combined Menin and XPO1 inhibition drive synergistic antileukemic activity in KMT2A r and NPM1 -m AML

doi: 10.64898/2026.03.10.710924

Figure Lengend Snippet: (A) Representative ChIP-qPCR analyses of indicated regions of Hoxa9 locus relative to the transcriptional start site (TSS) using an anti-menin antibody or IgG in KMT2A/MLLT3-immortalized myeloid progenitor cells treated with KPT-185 (500 nM) or DMSO for 6 hours. (B) Representative ChIP-qPCR analyses of indicated regions of Hoxa9 locus using an anti-XPO1 antibody in same cells as in (A). (C) Representative ChIP-qPCR analyses of indicated regions of Hoxa9 locus using an anti-menin antibody or IgG in KMT2A/MLLT3-immortalized myeloid progenitor cells treated with ziftomenib (50 nM) alone, selinexor (100 nM) alone, the combination, or DMSO for 6 hours. Percent of Input values for menin are presented after deduction of values for IgG. (D) Representative ChIP-qPCR analyses of indicated regions of Hoxa9 locus using an anti-XPO1 antibody in same cells as in (C) treated with selinexor (100 nM) or DMSO for 6 hours. Percent of Input values for XPO1 are presented after deduction of values for IgG. (E) Left panel, immunoprecipitates were prepared from nuclear extract of HEK293T cells transiently transfected with pMSCVpuro-KMT2A/MLLT3 using a menin-specific antibody or control IgG and analyzed by Western blotting analysis using indicated antibodies. Right panel, immunoprecipitates prepared from same nuclear extract using a KMT2A-N-specific antibody or IgG were analyzed by Western blotting analysis. (F) Immunoprecipitates were prepared from nuclear extract of HEK293T cells transiently transfected with pMSCVpuro-KMT2A/MLLT3 and treated with ziftomenib (50 nM) alone, selinexor (100 nM) alone, the combination, or DMSO for 6 hours using a menin-specific antibody and analyzed by Western blotting analysis using indicated antibodies. (G) Real-time RT-PCR analysis of Hoxa9 (left panel) and Meis1 (right panel) mRNA levels in KMT2A/MLLT3-immortalized myeloid progenitors transduced with indicated empty pMYs retrovirus (Vector) or pMYs virus expressing menin NES mutants (NES1, NES2, and NES1+2) in combination with a lentiviral shRNA targeting 3’UTR of endogenous Men1 (Men1-sh) or a non-targeting shRNA (NC-sh). Bottom panel, Western blotting analysis of menin expression in the co-transduced cells. (H) MV4;11 cells were treated with selinexor (or vehicle control, as indicated), followed by ChIP-qPCR using an anti-menin antibody (left panel) and anti-XPO1 antibody (right panel). qPCR was performed with primers spanning the indicated regions across the HOXA9 locus. ChIP enrichment is plotted as percent input (% input) for each amplicon; IgG served as a negative control. Bars represent the measured enrichment for each condition. (I) ChIP-qPCR using an anti-menin antibody in MV4;11 cells to map occupancy across the HOXA9 locus following treatment with vehicle control, ziftomenib, selinexor, or the combination.

Article Snippet: MV4;11 and MOLM13 cell lines were purchased from the American Type Culture Collection (ATCC, Manassas, VA, USA).

Techniques: ChIP-qPCR, Transfection, Control, Western Blot, Quantitative RT-PCR, Transduction, Plasmid Preparation, Virus, Expressing, shRNA, Amplification, Negative Control

Journal: bioRxiv

Article Title: Combined Menin and XPO1 inhibition drive synergistic antileukemic activity in KMT2A r and NPM1 -m AML

doi: 10.64898/2026.03.10.710924

Figure Lengend Snippet: (A-C) Survival of MV4;11 cell line-derived xenograft mice treated with metronomic doses of the ziftomenib and selinexor, and in combination. (D-F) Percentage of human CD45 positive cells in the peripheral blood of MV4;11 cell line-derived xenograft mice groups two weeks post last treatment (3 mice/group) with different doses of ziftomenib and selinexor. (G) Survival of GFP/Luciferase positive OCI-AML3 cell line-derived xenograft mice treated with ziftomenib and selinexor, and with combination. (H) Bioluminescence from luciferase in different groups of GFP/Luciferase-positive OCI-AML3 cell line-derived xenograft mice.

Article Snippet: MV4;11 and MOLM13 cell lines were purchased from the American Type Culture Collection (ATCC, Manassas, VA, USA).

Techniques: Derivative Assay, Luciferase