Fig. 1.
L1 drives HSC aging and affects prognosis of chronic myelomonocytic leukemia. a Quantitative real-time PCR (Q-PCR) analysis of the relative mRNA expression level of L1 in BM of WT and G3Terc−/− mice (n = 4, left). The protein levels of L1 (ORF1p) was determined by western blot in BM of WT and G3Terc−/− mice. The graph represents the relative ORF1p protein abundance (right). b Q-PCR analysis of the relative cDNA levels of L1 in BM cytoplasmic fraction of WT and G3Terc−/− mice (n = 3). c 2’3’-cGAMP levels were determined by LC-MS/MS in BM of WT and G3Terc−/− mice (n = 3). d Q-PCR analysis of the relative mRNA expression levels of IFNα and IFNβ in WT and G3Terc−/− mice (n = 5). e Q-PCR analysis of the relative mRNA expression levels of IFNα and IFNβ in G3Terc−/− and G3Terc−/−cGAS−/− mice (n = 3). f Q−PCR analysis of the relative cDNA levels of L1 in BM cytoplasmic fraction of WT or G3Terc−/− mice treated with or without 3TC (n = 3). g 2’3’-cGAMP levels were determined by LC-MS/MS in BM of WT or G3Terc−/− mice treated with or without 3TC (n ≥ 5). h Q-PCR analysis of the relative mRNA expression levels of IFNα and IFNβ in BM of WT or G3Terc−/− mice treated with or without 3TC (n = 3). i Q-PCR analysis of relative mRNA expression levels of L1, IFNα, IFNβ, and IL-6 in control and L1 depleted BM cells of G3Terc−/− mice (n = 5). j Numbers of LT (CD34−Flt3−LSK), ST(CD34+Flt3− LSK) and MPP (CD34+Flt3+ LSK) per million BM cells of WT, or G3Terc−/− mice treated with or without 3TC (n = 5). k Percentage of donor-derived PB cells of G3Terc−/− mice treated with or without 3TC at the indicated time points in competitive transplantation assay (n ≥ 3). l Percentage of donor-derived LT in BM of G3Terc−/− mice and 3TC-treated G3Terc−/− mice 16 weeks after transplantation (n ≥ 4). m Survival curve of WT recipient mice and G3Terc−/− recipient mice following transplantation (n = 20). n Absolute number of M, T, and B cells in BM of WT recipient mice and G3Terc−/− recipient mice (n ≥ 8). o Absolute number of LT, ST, MPP, GMP (granulocyte/monocyte progenitor CD34+CD16/32+Sca1−c-Kit+ Lin−), CMP (common myeloid progenitor, CD34+CD16/32−Sca1−c-Kit+Lin−), MEP (megakaryocyte /erythrocyte progenitor, CD34−CD16/32−Sca1−c-Kit+Lin−), and CLP (common lymphoid progenitor, Flt3+ IL-7R+c-KitmidSca1midLin−) in recipient-derived BM of WT recipient mice and G3Terc−/− recipient mice (n ≥ 7). p Absolute number of LT, ST, MPP, GMP, CMP, MEP, and CLP in donor-derived BM of WT recipient mice and G3Terc−/− recipient mice (n ≥ 5). q Survival curve of WT recipient or G3Terc−/− recipient mice treated with or without 3TC following transplantation (n ≥ 10). r Absolute number of M, T, and B cells in BM of G3Terc−/− recipient mice treated with or without 3TC (n ≥ 7). s Absolute number of LT, ST, MPP, GMP, CMP, MEP, MKP (IL-7R−CD41+c-Kit+ Lin−) and CLP in donor-derived BM of G3Terc−/− recipient mice treated with or without 3TC (n ≥ 6). t Absolute number of LT, ST, MPP, GMP, CMP, MEP, MKP, and CLP in recipient-derived BM of G3Terc−/− recipient mice treated with or without 3TC (n ≥ 7). *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001