Figure 3.
Prolonged XPO1 inhibition is necessary to induce terminal differentiation of NPM1-mutated cells in vitro. (A) HOXA9, HOXA10, and MEIS1 expression by qPCR in OCI-AML3 cells after 24 hours treatment with DMSO, selinexor, or eltanexor 50 nM; 72 hours treatment with DMSO, selinexor, or eltanexor 50 nM 5 days per week (72 hours treatment); and selinexor or eltanexor 2 days per week (24 hours treatment + 48 hours fresh medium). N = 3, mean ± SEM, Tukey multiple comparison test. (B) May-Grünwald Giemsa staining of OCI-AML3 cells on day 11 following treatment with either DMSO, selinexor, or eltanexor 50 nM 2 days per week and selinexor or eltanexor 50 nM 5 days per week. Original magnification ×40. Uncropped images are shown in supplemental Figure 4A. (C) Flow cytometry quantification of CD11b, expressed as MFI FC relative to DMSO in OCI-AML3 cells on day 11 of treatment with either DMSO, selinexor or eltanexor 50 nM 2 days per week and selinexor or eltanexor 50 nM 5 days per week. N = 3, mean ± SEM, Tukey multiple comparison test. (D) Histogram plots representing CD11b expression analyzed by flow cytometry on day 11 in OCI-AML3 cells treated with DMSO, selinexor, or eltanexor 50 nM 2 days per week and selinexor or eltanexor 50 nM 5 days per week. (E) Flow cytometry quantification of CD11b, expressed as MFI FC relative to DMSO in OCI-AML3 cells on day 11 of treatment with 2 days per week DMSO, selinexor 50 nM, or selinexor 100 nM. N = 3, mean ± SEM, Tukey multiple comparison test. (F) Histogram plot representing CD11b expression analyzed by flow cytometry on day 11 in OCI-AML3 cells treated with either DMSO and selinexor 50 nM or 100 nM 2 days per week. (G) Flow cytometry quantification of CD11b, expressed as MFI FC relative to DMSO in 4 primary NPM1-mutated AML samples and 2 PDXs after 7 to 9 days of treatment with DMSO, 50 nM selinexor or eltanexor 2 days per week, or 50 nM selinexor or eltanexor 5 days per week. N ≥ 2 for each patient/PDX, mean ± SEM, Tukey multiple comparison test on each patient/PDX. (H) Histogram plot representing CD11b expression analyzed by flow cytometry on day 7 in UPN03 and UPN02 primary AML cells treated with either DMSO or selinexor or eltanexor 50 nM 5 days per week. (I) Flow cytometry quantification of CD11b, expressed as MFI FC relative to DMSO in untransduced and HOXA9/MEIS1-transduced OCI-AML3 cells after 7 days of CT with either DMSO or selinexor 50 nM. N = 4, mean ± SEM, Tukey multiple comparison test. (J) Histogram plot showing CD11b expression analyzed by flow cytometry on day 7 in untransduced and HOXA9/MEIS1-transduced OCI-AML3 cells treated with either DMSO or selinexor 50 nM for 7 consecutive days. Elta, eltanexor; UPN, unique patient number; H9/M1, HOXA9/MEIS1.

Prolonged XPO1 inhibition is necessary to induce terminal differentiation of NPM1-mutated cells in vitro. (A) HOXA9, HOXA10, and MEIS1 expression by qPCR in OCI-AML3 cells after 24 hours treatment with DMSO, selinexor, or eltanexor 50 nM; 72 hours treatment with DMSO, selinexor, or eltanexor 50 nM 5 days per week (72 hours treatment); and selinexor or eltanexor 2 days per week (24 hours treatment + 48 hours fresh medium). N = 3, mean ± SEM, Tukey multiple comparison test. (B) May-Grünwald Giemsa staining of OCI-AML3 cells on day 11 following treatment with either DMSO, selinexor, or eltanexor 50 nM 2 days per week and selinexor or eltanexor 50 nM 5 days per week. Original magnification ×40. Uncropped images are shown in supplemental Figure 4A. (C) Flow cytometry quantification of CD11b, expressed as MFI FC relative to DMSO in OCI-AML3 cells on day 11 of treatment with either DMSO, selinexor or eltanexor 50 nM 2 days per week and selinexor or eltanexor 50 nM 5 days per week. N = 3, mean ± SEM, Tukey multiple comparison test. (D) Histogram plots representing CD11b expression analyzed by flow cytometry on day 11 in OCI-AML3 cells treated with DMSO, selinexor, or eltanexor 50 nM 2 days per week and selinexor or eltanexor 50 nM 5 days per week. (E) Flow cytometry quantification of CD11b, expressed as MFI FC relative to DMSO in OCI-AML3 cells on day 11 of treatment with 2 days per week DMSO, selinexor 50 nM, or selinexor 100 nM. N = 3, mean ± SEM, Tukey multiple comparison test. (F) Histogram plot representing CD11b expression analyzed by flow cytometry on day 11 in OCI-AML3 cells treated with either DMSO and selinexor 50 nM or 100 nM 2 days per week. (G) Flow cytometry quantification of CD11b, expressed as MFI FC relative to DMSO in 4 primary NPM1-mutated AML samples and 2 PDXs after 7 to 9 days of treatment with DMSO, 50 nM selinexor or eltanexor 2 days per week, or 50 nM selinexor or eltanexor 5 days per week. N ≥ 2 for each patient/PDX, mean ± SEM, Tukey multiple comparison test on each patient/PDX. (H) Histogram plot representing CD11b expression analyzed by flow cytometry on day 7 in UPN03 and UPN02 primary AML cells treated with either DMSO or selinexor or eltanexor 50 nM 5 days per week. (I) Flow cytometry quantification of CD11b, expressed as MFI FC relative to DMSO in untransduced and HOXA9/MEIS1-transduced OCI-AML3 cells after 7 days of CT with either DMSO or selinexor 50 nM. N = 4, mean ± SEM, Tukey multiple comparison test. (J) Histogram plot showing CD11b expression analyzed by flow cytometry on day 7 in untransduced and HOXA9/MEIS1-transduced OCI-AML3 cells treated with either DMSO or selinexor 50 nM for 7 consecutive days. Elta, eltanexor; UPN, unique patient number; H9/M1, HOXA9/MEIS1.

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