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Responses to revumenib in <t>KMT2A</t> -rearranged AML and ALL cells. ( A ) Cell viability in response to increasing concentrations of revumenib as assessed by 4-day MTT assays in KMT2A -rearranged (n = 6) and wildtype KMT2A (n = 3) <t>AML</t> <t>cell</t> line models. The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates and data consisted of three biological replicates. ( B ) IC 50 -values (i.e., the inhibitory concentration to 50% of the leukemic cells) for revumenib as determined by nonlinear regression in KMT2A -rearranged and wildtype KMT2A AML cell lines, statistically evaluated by an unpaired two-tailed t -test, with ns showing no significant differences. ( C ) Cell viability in response to increasing concentrations of revumenib using 4-day MTT assays in ex vivo pediatric KMT2A -rearranged AML patient samples obtained from patient-derived xenograft mouse models (n = 3). The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates. ( D ) Cell viability in response to increasing concentrations of revumenib as assessed by 4-day MTT assays in KMT2A -rearranged ALL cell line models (n = 5) and wildtype KMT2A ALL cell lines (n = 2). The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates and data consisted of three biological replicates. ( E ) IC 50 -values for revumenib as determined by nonlinear regression in KMT2A -rearranged and wildtype KMT2A ALL cell lines, statistically evaluated by an unpaired two-tailed t -test; * p < 0.05 ( F ) Cell viability in response to increasing concentrations of revumenib using 4-day MTT assays in ex vivo pediatric KMT2A -rearranged ALL patient samples (n = 5). The dashed line shows the 50% viability threshold Experiments were performed in technical triplicates.
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Responses to revumenib in <t>KMT2A</t> -rearranged AML and ALL cells. ( A ) Cell viability in response to increasing concentrations of revumenib as assessed by 4-day MTT assays in KMT2A -rearranged (n = 6) and wildtype KMT2A (n = 3) <t>AML</t> <t>cell</t> line models. The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates and data consisted of three biological replicates. ( B ) IC 50 -values (i.e., the inhibitory concentration to 50% of the leukemic cells) for revumenib as determined by nonlinear regression in KMT2A -rearranged and wildtype KMT2A AML cell lines, statistically evaluated by an unpaired two-tailed t -test, with ns showing no significant differences. ( C ) Cell viability in response to increasing concentrations of revumenib using 4-day MTT assays in ex vivo pediatric KMT2A -rearranged AML patient samples obtained from patient-derived xenograft mouse models (n = 3). The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates. ( D ) Cell viability in response to increasing concentrations of revumenib as assessed by 4-day MTT assays in KMT2A -rearranged ALL cell line models (n = 5) and wildtype KMT2A ALL cell lines (n = 2). The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates and data consisted of three biological replicates. ( E ) IC 50 -values for revumenib as determined by nonlinear regression in KMT2A -rearranged and wildtype KMT2A ALL cell lines, statistically evaluated by an unpaired two-tailed t -test; * p < 0.05 ( F ) Cell viability in response to increasing concentrations of revumenib using 4-day MTT assays in ex vivo pediatric KMT2A -rearranged ALL patient samples (n = 5). The dashed line shows the 50% viability threshold Experiments were performed in technical triplicates.
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Responses to revumenib in <t>KMT2A</t> -rearranged AML and ALL cells. ( A ) Cell viability in response to increasing concentrations of revumenib as assessed by 4-day MTT assays in KMT2A -rearranged (n = 6) and wildtype KMT2A (n = 3) <t>AML</t> <t>cell</t> line models. The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates and data consisted of three biological replicates. ( B ) IC 50 -values (i.e., the inhibitory concentration to 50% of the leukemic cells) for revumenib as determined by nonlinear regression in KMT2A -rearranged and wildtype KMT2A AML cell lines, statistically evaluated by an unpaired two-tailed t -test, with ns showing no significant differences. ( C ) Cell viability in response to increasing concentrations of revumenib using 4-day MTT assays in ex vivo pediatric KMT2A -rearranged AML patient samples obtained from patient-derived xenograft mouse models (n = 3). The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates. ( D ) Cell viability in response to increasing concentrations of revumenib as assessed by 4-day MTT assays in KMT2A -rearranged ALL cell line models (n = 5) and wildtype KMT2A ALL cell lines (n = 2). The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates and data consisted of three biological replicates. ( E ) IC 50 -values for revumenib as determined by nonlinear regression in KMT2A -rearranged and wildtype KMT2A ALL cell lines, statistically evaluated by an unpaired two-tailed t -test; * p < 0.05 ( F ) Cell viability in response to increasing concentrations of revumenib using 4-day MTT assays in ex vivo pediatric KMT2A -rearranged ALL patient samples (n = 5). The dashed line shows the 50% viability threshold Experiments were performed in technical triplicates.
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Responses to revumenib in <t>KMT2A</t> -rearranged AML and ALL cells. ( A ) Cell viability in response to increasing concentrations of revumenib as assessed by 4-day MTT assays in KMT2A -rearranged (n = 6) and wildtype KMT2A (n = 3) <t>AML</t> <t>cell</t> line models. The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates and data consisted of three biological replicates. ( B ) IC 50 -values (i.e., the inhibitory concentration to 50% of the leukemic cells) for revumenib as determined by nonlinear regression in KMT2A -rearranged and wildtype KMT2A AML cell lines, statistically evaluated by an unpaired two-tailed t -test, with ns showing no significant differences. ( C ) Cell viability in response to increasing concentrations of revumenib using 4-day MTT assays in ex vivo pediatric KMT2A -rearranged AML patient samples obtained from patient-derived xenograft mouse models (n = 3). The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates. ( D ) Cell viability in response to increasing concentrations of revumenib as assessed by 4-day MTT assays in KMT2A -rearranged ALL cell line models (n = 5) and wildtype KMT2A ALL cell lines (n = 2). The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates and data consisted of three biological replicates. ( E ) IC 50 -values for revumenib as determined by nonlinear regression in KMT2A -rearranged and wildtype KMT2A ALL cell lines, statistically evaluated by an unpaired two-tailed t -test; * p < 0.05 ( F ) Cell viability in response to increasing concentrations of revumenib using 4-day MTT assays in ex vivo pediatric KMT2A -rearranged ALL patient samples (n = 5). The dashed line shows the 50% viability threshold Experiments were performed in technical triplicates.
Gene Exp Mll Aff1 Fusion Hs03024412 Ft, supplied by Thermo Fisher, used in various techniques. Bioz Stars score: 92/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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Image Search Results


Responses to revumenib in KMT2A -rearranged AML and ALL cells. ( A ) Cell viability in response to increasing concentrations of revumenib as assessed by 4-day MTT assays in KMT2A -rearranged (n = 6) and wildtype KMT2A (n = 3) AML cell line models. The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates and data consisted of three biological replicates. ( B ) IC 50 -values (i.e., the inhibitory concentration to 50% of the leukemic cells) for revumenib as determined by nonlinear regression in KMT2A -rearranged and wildtype KMT2A AML cell lines, statistically evaluated by an unpaired two-tailed t -test, with ns showing no significant differences. ( C ) Cell viability in response to increasing concentrations of revumenib using 4-day MTT assays in ex vivo pediatric KMT2A -rearranged AML patient samples obtained from patient-derived xenograft mouse models (n = 3). The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates. ( D ) Cell viability in response to increasing concentrations of revumenib as assessed by 4-day MTT assays in KMT2A -rearranged ALL cell line models (n = 5) and wildtype KMT2A ALL cell lines (n = 2). The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates and data consisted of three biological replicates. ( E ) IC 50 -values for revumenib as determined by nonlinear regression in KMT2A -rearranged and wildtype KMT2A ALL cell lines, statistically evaluated by an unpaired two-tailed t -test; * p < 0.05 ( F ) Cell viability in response to increasing concentrations of revumenib using 4-day MTT assays in ex vivo pediatric KMT2A -rearranged ALL patient samples (n = 5). The dashed line shows the 50% viability threshold Experiments were performed in technical triplicates.

Journal: International Journal of Molecular Sciences

Article Title: Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in KMT2A -Rearranged Acute Lymphoblastic and Myeloid Leukemia

doi: 10.3390/ijms25116020

Figure Lengend Snippet: Responses to revumenib in KMT2A -rearranged AML and ALL cells. ( A ) Cell viability in response to increasing concentrations of revumenib as assessed by 4-day MTT assays in KMT2A -rearranged (n = 6) and wildtype KMT2A (n = 3) AML cell line models. The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates and data consisted of three biological replicates. ( B ) IC 50 -values (i.e., the inhibitory concentration to 50% of the leukemic cells) for revumenib as determined by nonlinear regression in KMT2A -rearranged and wildtype KMT2A AML cell lines, statistically evaluated by an unpaired two-tailed t -test, with ns showing no significant differences. ( C ) Cell viability in response to increasing concentrations of revumenib using 4-day MTT assays in ex vivo pediatric KMT2A -rearranged AML patient samples obtained from patient-derived xenograft mouse models (n = 3). The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates. ( D ) Cell viability in response to increasing concentrations of revumenib as assessed by 4-day MTT assays in KMT2A -rearranged ALL cell line models (n = 5) and wildtype KMT2A ALL cell lines (n = 2). The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates and data consisted of three biological replicates. ( E ) IC 50 -values for revumenib as determined by nonlinear regression in KMT2A -rearranged and wildtype KMT2A ALL cell lines, statistically evaluated by an unpaired two-tailed t -test; * p < 0.05 ( F ) Cell viability in response to increasing concentrations of revumenib using 4-day MTT assays in ex vivo pediatric KMT2A -rearranged ALL patient samples (n = 5). The dashed line shows the 50% viability threshold Experiments were performed in technical triplicates.

Article Snippet: The KMT2A -rearranged AML cell lines include MV4-11 ( KMT2A::AFF1 + ; DMSZ: ACC 102), ML2 ( KMT2A::AFDN + ; DMSZ: ACC 15), SHI-1 ( KMT2A::AFDN + ; DSMZ: ACC 645), NOMO-1 ( KMT2A::MLLT3 + ; DSMZ: ACC 542), THP-1 ( KMT2A::MLLT3 + ; DSMZ: ACC 16), and MONO-MAC-1 ( KMT2A::MLLT3 + ; DSMZ: ACC 252), and the wildtype KMT2A AML cell lines include HL-60 (DMSZ: ACC 3), Kasumi-1 (AML1-ETO); DSMZ: ACC 220), and OCI-AML3 (NPM1 mutated; DSMZ: ACC 582).

Techniques: Concentration Assay, Two Tailed Test, Ex Vivo, Derivative Assay

Prolonged revumenib exposure induces myeloid differentiation in KMT2A -rearranged AML cells. ( A ) Percentage of viable cells after 7 and 14-day exposures to indicated concentrations of revumenib as determined by trypan blue exclusion in KMT2A -rearranged AML cell line models (n = 5). Responsive cell lines are in blue and unresponsive cell lines are in purple. The dashed line shows the 50% viability threshold. Experiments were performed in technical duplicates and data consisted of two biological replicates. ( B ) Percentages of live (grey), apoptotic (orange), and dead (red) cells after 7 and 14-day exposures to indicated concentrations of revumenib as determined by an Annexin V/7AAD staining and flowcytometry in KMT2A -rearranged AML cell line models. Differences in live, apoptotic, and death cells induced by revumenib as compared to untreated controls were statistically verified by two-way ANOVA Tukey’s multiple comparisons tests. Data consisted of two biological replicates. ( C ) Flow cytometric assessment of the expression of the myeloid differentiation marker CD14 and of stem cell marker CD117 (c-Kit) after 7 and 14 days of revumenib exposure in the responsive KMT2A -rearranged AML cell lines SHI-1, MONO-MAC-1, and NOMO-1, from duplicate experiments. * p < 0.05, ** p < 0.005, *** p < 0.0005, **** p < 0.00005 and ns for no significant p .

Journal: International Journal of Molecular Sciences

Article Title: Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in KMT2A -Rearranged Acute Lymphoblastic and Myeloid Leukemia

doi: 10.3390/ijms25116020

Figure Lengend Snippet: Prolonged revumenib exposure induces myeloid differentiation in KMT2A -rearranged AML cells. ( A ) Percentage of viable cells after 7 and 14-day exposures to indicated concentrations of revumenib as determined by trypan blue exclusion in KMT2A -rearranged AML cell line models (n = 5). Responsive cell lines are in blue and unresponsive cell lines are in purple. The dashed line shows the 50% viability threshold. Experiments were performed in technical duplicates and data consisted of two biological replicates. ( B ) Percentages of live (grey), apoptotic (orange), and dead (red) cells after 7 and 14-day exposures to indicated concentrations of revumenib as determined by an Annexin V/7AAD staining and flowcytometry in KMT2A -rearranged AML cell line models. Differences in live, apoptotic, and death cells induced by revumenib as compared to untreated controls were statistically verified by two-way ANOVA Tukey’s multiple comparisons tests. Data consisted of two biological replicates. ( C ) Flow cytometric assessment of the expression of the myeloid differentiation marker CD14 and of stem cell marker CD117 (c-Kit) after 7 and 14 days of revumenib exposure in the responsive KMT2A -rearranged AML cell lines SHI-1, MONO-MAC-1, and NOMO-1, from duplicate experiments. * p < 0.05, ** p < 0.005, *** p < 0.0005, **** p < 0.00005 and ns for no significant p .

Article Snippet: The KMT2A -rearranged AML cell lines include MV4-11 ( KMT2A::AFF1 + ; DMSZ: ACC 102), ML2 ( KMT2A::AFDN + ; DMSZ: ACC 15), SHI-1 ( KMT2A::AFDN + ; DSMZ: ACC 645), NOMO-1 ( KMT2A::MLLT3 + ; DSMZ: ACC 542), THP-1 ( KMT2A::MLLT3 + ; DSMZ: ACC 16), and MONO-MAC-1 ( KMT2A::MLLT3 + ; DSMZ: ACC 252), and the wildtype KMT2A AML cell lines include HL-60 (DMSZ: ACC 3), Kasumi-1 (AML1-ETO); DSMZ: ACC 220), and OCI-AML3 (NPM1 mutated; DSMZ: ACC 582).

Techniques: Staining, Expressing, Marker

Revumenib readily induces apoptosis in KMT2A -rearranged ALL cells. ( A ) Percentage of viable cells after 4-day exposures to indicated concentrations of revumenib as determined by trypan blue exclusion in KMT2A -rearranged ALL cell line models (n = 5; in orange) and the highly sensitive KMT2A -rearranged AML cell line MV4-11 (in blue). The dashed line shows the 50% viability threshold. Experiments were performed in technical duplicates and data consisted of two biological replicates. ( B ) Percentages of live (grey), apoptotic (orange), and dead (red) cells after 4-day exposures to indicated concentrations of revumenib as determined by flow cytometry and Annexin V/7AAD staining in the KMT2A -rearranged AML cell line MV4-11 and ( C ) in the KMT2A -rearranged ALL cell lines. Differences in live, apoptotic, and death cells induced by revumenib as compared to untreated controls were statistically verified by two-way ANOVA Tukey’s multiple comparisons tests. Data consisted of two biological replicates. ( D ) Cell cycle analysis showing the percentages of cells residing in the G1-phase, S-phase, and GM2-phase as determined by Hoechst 33342/7AAD staining and flow cytometry after 4-day exposures to indicated concentrations of revumenib. Differences in cell cycle phases induced by revumenib as compared to untreated controls were statistically verified by two-way ANOVA Tukey’s multiple comparisons tests. Data consisted of two biological replicates. ( E ) Cell viability (as determined by trypan blue exclusion) and cell cycle analysis (as determined by Hoechst 33342/7AAD staining and flow cytometry) after 4-day exposures to indicated concentrations of revumenib in a representative KMT2A -rearranged infant ALL patient sample obtained from a patient-derived xenograft mouse model. The dashed line shows the 50% viability threshold. * p < 0.05, ** p < 0.005, **** p < 0.00005 and ns for no significant p .

Journal: International Journal of Molecular Sciences

Article Title: Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in KMT2A -Rearranged Acute Lymphoblastic and Myeloid Leukemia

doi: 10.3390/ijms25116020

Figure Lengend Snippet: Revumenib readily induces apoptosis in KMT2A -rearranged ALL cells. ( A ) Percentage of viable cells after 4-day exposures to indicated concentrations of revumenib as determined by trypan blue exclusion in KMT2A -rearranged ALL cell line models (n = 5; in orange) and the highly sensitive KMT2A -rearranged AML cell line MV4-11 (in blue). The dashed line shows the 50% viability threshold. Experiments were performed in technical duplicates and data consisted of two biological replicates. ( B ) Percentages of live (grey), apoptotic (orange), and dead (red) cells after 4-day exposures to indicated concentrations of revumenib as determined by flow cytometry and Annexin V/7AAD staining in the KMT2A -rearranged AML cell line MV4-11 and ( C ) in the KMT2A -rearranged ALL cell lines. Differences in live, apoptotic, and death cells induced by revumenib as compared to untreated controls were statistically verified by two-way ANOVA Tukey’s multiple comparisons tests. Data consisted of two biological replicates. ( D ) Cell cycle analysis showing the percentages of cells residing in the G1-phase, S-phase, and GM2-phase as determined by Hoechst 33342/7AAD staining and flow cytometry after 4-day exposures to indicated concentrations of revumenib. Differences in cell cycle phases induced by revumenib as compared to untreated controls were statistically verified by two-way ANOVA Tukey’s multiple comparisons tests. Data consisted of two biological replicates. ( E ) Cell viability (as determined by trypan blue exclusion) and cell cycle analysis (as determined by Hoechst 33342/7AAD staining and flow cytometry) after 4-day exposures to indicated concentrations of revumenib in a representative KMT2A -rearranged infant ALL patient sample obtained from a patient-derived xenograft mouse model. The dashed line shows the 50% viability threshold. * p < 0.05, ** p < 0.005, **** p < 0.00005 and ns for no significant p .

Article Snippet: The KMT2A -rearranged AML cell lines include MV4-11 ( KMT2A::AFF1 + ; DMSZ: ACC 102), ML2 ( KMT2A::AFDN + ; DMSZ: ACC 15), SHI-1 ( KMT2A::AFDN + ; DSMZ: ACC 645), NOMO-1 ( KMT2A::MLLT3 + ; DSMZ: ACC 542), THP-1 ( KMT2A::MLLT3 + ; DSMZ: ACC 16), and MONO-MAC-1 ( KMT2A::MLLT3 + ; DSMZ: ACC 252), and the wildtype KMT2A AML cell lines include HL-60 (DMSZ: ACC 3), Kasumi-1 (AML1-ETO); DSMZ: ACC 220), and OCI-AML3 (NPM1 mutated; DSMZ: ACC 582).

Techniques: Flow Cytometry, Staining, Cell Cycle Assay, Derivative Assay

Induction of acquired resistance to revumenib in KMT2A -rearranged ALL cells. Induction of acquired resistance to revumenib was accomplished by exposing the KMT2A::AFF1 + ALL cell lines SEM and RS4;11 to increasing concentrations of revumenib of up to 10 µM for 10 weeks. Revumenib-resistant daughter cell lines are indicated as SEM REV_RES#1–4 and RS4;11 REV_RES#1–4 , respectively. ( A ) Cell viability in response to increasing concentrations of revumenib as assessed by 4-day MTT assays in SEM (orange) and revumenib-resistant daughter cell lines SEM REV_RES#1–4 (purple). The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates and data consisted of three biological replicates. ( B ) IC 50 -values for revumenib as determined by nonlinear regression in SEM (orange) and revumenib-resistant daughter cell lines SEM REV_RES#1–4 (purple) evaluated by an unpaired two-tailed t -test. ( C ) MEN1 mutation analysis (i.e., Sanger sequencing results) showing an M322T MEN1 mutation in all revumenib-resistant SEM daughter lines SEM REV_RES#1–4 (blue). ( D ) Cell viability in response to increasing concentrations of revumenib as assessed by 4-day MTT assays in RS4;11 (orange) and revumenib-resistant daughter cell lines RS4;11 REV_RES#1–4 (purple). The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates and data consisted of three biological replicates. ( E ) IC 50 -values for revumenib as determined by nonlinear regression in RS4;11 (orange) and revumenib-resistant daughter cell lines RS4;11 REV_RES#1–4 (purple) evaluated by an unpaired two-tailed t -test. ( F ) MEN1 mutation analysis reveals an M322T MEN1 mutation only in revumenib-resistant RS4;11 REV_RES#2 cells (blue).

Journal: International Journal of Molecular Sciences

Article Title: Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in KMT2A -Rearranged Acute Lymphoblastic and Myeloid Leukemia

doi: 10.3390/ijms25116020

Figure Lengend Snippet: Induction of acquired resistance to revumenib in KMT2A -rearranged ALL cells. Induction of acquired resistance to revumenib was accomplished by exposing the KMT2A::AFF1 + ALL cell lines SEM and RS4;11 to increasing concentrations of revumenib of up to 10 µM for 10 weeks. Revumenib-resistant daughter cell lines are indicated as SEM REV_RES#1–4 and RS4;11 REV_RES#1–4 , respectively. ( A ) Cell viability in response to increasing concentrations of revumenib as assessed by 4-day MTT assays in SEM (orange) and revumenib-resistant daughter cell lines SEM REV_RES#1–4 (purple). The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates and data consisted of three biological replicates. ( B ) IC 50 -values for revumenib as determined by nonlinear regression in SEM (orange) and revumenib-resistant daughter cell lines SEM REV_RES#1–4 (purple) evaluated by an unpaired two-tailed t -test. ( C ) MEN1 mutation analysis (i.e., Sanger sequencing results) showing an M322T MEN1 mutation in all revumenib-resistant SEM daughter lines SEM REV_RES#1–4 (blue). ( D ) Cell viability in response to increasing concentrations of revumenib as assessed by 4-day MTT assays in RS4;11 (orange) and revumenib-resistant daughter cell lines RS4;11 REV_RES#1–4 (purple). The dashed line shows the 50% viability threshold. Experiments were performed in technical triplicates and data consisted of three biological replicates. ( E ) IC 50 -values for revumenib as determined by nonlinear regression in RS4;11 (orange) and revumenib-resistant daughter cell lines RS4;11 REV_RES#1–4 (purple) evaluated by an unpaired two-tailed t -test. ( F ) MEN1 mutation analysis reveals an M322T MEN1 mutation only in revumenib-resistant RS4;11 REV_RES#2 cells (blue).

Article Snippet: The KMT2A -rearranged AML cell lines include MV4-11 ( KMT2A::AFF1 + ; DMSZ: ACC 102), ML2 ( KMT2A::AFDN + ; DMSZ: ACC 15), SHI-1 ( KMT2A::AFDN + ; DSMZ: ACC 645), NOMO-1 ( KMT2A::MLLT3 + ; DSMZ: ACC 542), THP-1 ( KMT2A::MLLT3 + ; DSMZ: ACC 16), and MONO-MAC-1 ( KMT2A::MLLT3 + ; DSMZ: ACC 252), and the wildtype KMT2A AML cell lines include HL-60 (DMSZ: ACC 3), Kasumi-1 (AML1-ETO); DSMZ: ACC 220), and OCI-AML3 (NPM1 mutated; DSMZ: ACC 582).

Techniques: Two Tailed Test, Mutagenesis, Sequencing

Synergy between revumenib and pinometostat in KMT2A -rearranged ALL. Three-dimensional synergy plots showing drug synergy (red) or antagonism (green) between indicated concentrations of revumenib (x-axis) and pinometostat (y-axis) as determined by 6-day pinometostat pre-treated cells followed by 4-day MTT assays of revumenib exposures in ( A ) KMT2A -rearranged ALL cell lines, ( B ) a PDX derived KMT2A -rearranged infant ALL patient sample, and ( C ) KMT2A -rearranged AML cell lines. Drug synergy/antagonism is expressed as Zero Interaction Potency (ZIP) scores (z-axis), with scores of >5 being considered as synergistic effects (red areas), and ZIP scores below −5 are deemed as antagonistic effects (green areas). On top of each 3D synergy plot, the average ZIP score over the entire range of pinometostat and revumenib concentrations is listed.

Journal: International Journal of Molecular Sciences

Article Title: Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in KMT2A -Rearranged Acute Lymphoblastic and Myeloid Leukemia

doi: 10.3390/ijms25116020

Figure Lengend Snippet: Synergy between revumenib and pinometostat in KMT2A -rearranged ALL. Three-dimensional synergy plots showing drug synergy (red) or antagonism (green) between indicated concentrations of revumenib (x-axis) and pinometostat (y-axis) as determined by 6-day pinometostat pre-treated cells followed by 4-day MTT assays of revumenib exposures in ( A ) KMT2A -rearranged ALL cell lines, ( B ) a PDX derived KMT2A -rearranged infant ALL patient sample, and ( C ) KMT2A -rearranged AML cell lines. Drug synergy/antagonism is expressed as Zero Interaction Potency (ZIP) scores (z-axis), with scores of >5 being considered as synergistic effects (red areas), and ZIP scores below −5 are deemed as antagonistic effects (green areas). On top of each 3D synergy plot, the average ZIP score over the entire range of pinometostat and revumenib concentrations is listed.

Article Snippet: The KMT2A -rearranged AML cell lines include MV4-11 ( KMT2A::AFF1 + ; DMSZ: ACC 102), ML2 ( KMT2A::AFDN + ; DMSZ: ACC 15), SHI-1 ( KMT2A::AFDN + ; DSMZ: ACC 645), NOMO-1 ( KMT2A::MLLT3 + ; DSMZ: ACC 542), THP-1 ( KMT2A::MLLT3 + ; DSMZ: ACC 16), and MONO-MAC-1 ( KMT2A::MLLT3 + ; DSMZ: ACC 252), and the wildtype KMT2A AML cell lines include HL-60 (DMSZ: ACC 3), Kasumi-1 (AML1-ETO); DSMZ: ACC 220), and OCI-AML3 (NPM1 mutated; DSMZ: ACC 582).

Techniques: Derivative Assay