Journal: Communications Biology

Article Title: Targeting heterochromatin eliminates chronic myelomonocytic leukemia malignant stem cells through reactivation of retroelements and immune pathways

doi: 10.1038/s42003-024-07214-1

Figure Lengend Snippet: a Protocol scheme for the treatments with DAC ± UNC0638 and blocking IFN receptor (IFNAR2) antibodies. The anti-IFNAR2 antibody (1 µg/ml) was added on days 2 and 4 and the cells were seeded in methylcellulose on day 4. b Number of colonies at passages 1 and 2, reported to the non-treated condition. c Cumulative potential at passage 2. Results are reported to those obtained in the NT condition. Mean ± SEM; n = 6 patients. One-way ANOVA Bonferroni’s multiple comparison. * p < 0.05; *** p < 0.001; **** p < 0.0001. d Model illustrating the increase in H3K9me2 at TEs and repression of immune-associated transcripts in CMML HSPCs compared with age-matched healthy HSPCs (left). The mechanism repressing inflammatory gene is unknown but independent of H3K9me2. TEs are repressed by both H3K9me2 and DNA methylation in CMML cells, as shown by their reexpression only upon treatment with a combination of HMA and G9A/GLP inhibitors (right). Reexpression of TEs results in dsRNA formation, induction of IFN signaling and reactivation of the innate immune response in CMML HSCs, selectively targeting mutated cells while preserving residual wild-type HSCs. Left: Dark-blue cell, healthy donor HSC; red cells, CMML HSC. CMML mutated cells enter in apoptosis upon treatment with the combination. Right: red cell with a yellow star, CMML mutated HSC; light-blue cell, non-mutated HSC in CMML patients. The figure was created by AP and FP. Pictures from the cells are from Servier medical Art ( https://smart.servier.com/ ).

Article Snippet: Global DNA methylation was studied using the global DNA methylation assay kit—LINE-1 (Active Motif) according to the manufacturer’s instructions.

Techniques: Blocking Assay, Comparison, DNA Methylation Assay, Preserving