Acute myeloid leukemia fusion proteins deregulate genes involved in stem cell maintenance and DNA repair
J. Clin. Invest. Myriam Alcalay, et al. 112:1751 doi:10.1172/JCI17595 [
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Figure 3(
a) mRNA levels of Notch ligands in Mt, U937-PML/RAR and U937-AML1/ETO cells, assessed by real time RT-PCR. Relative expression levels are shown. (
b) Western blot analysis of Jagged1 protein expression in U937-PML/RAR and U937-AML1/ETO cells treated with 100 μM ZnSO
4 for the indicated number of hours. Jagged1 levels are shown in the top row, fusion protein expression in the middle row and lamin B expression in the bottom row. Jagged1 expression in Mt cells was not modified by ZnSO
4 treatment (data not shown). (
c) Relative mRNA levels of LFNG in U937 PML/RAR and U937 AML1/ETO cells. Mt was the control in panels
a and
c. (
d) LFNG mRNA levels dramatically increase after RA treatment in vitro of blasts from two different APL patients, as compared to the control (C); i.e., the same cells prior to treatment. (
e) Expression of PML/RAR or AML1/ETO in HeLa cells increases the activity of a Notch 1-responsive promoter. All values are plotted as relative fold activation. The black bar shows HES-Luc transactivation by an activated, intracellular domain of Notch 1 (ICD Notch1). (
f) Relative expression of
JAG1,
LFNG and
HES1 genes in blasts bearing the t(15;17) or the t(8;21) compared to CD34
+ cells, assayed by real time RT-PCR. The results shown are the average values obtained from cells derived from 7 different individuals for each condition. All RT-PCR data shown in this figure represents the average values of three independent measurements.
GAPDH gene expression was used for normalization. Fold mRNAs are calculated from real time curves.
