Figure 1.
Deletion of the 9p21 region in human cancers and genetic targeting of the 9p21s region in mice. (A) Schematic representation of the human 9p21 locus and the syntenic murine locus (9p21s). Genes and their 5′-3′ orientation are indicated by thick arrows (blue, green, and orange). A noncoding RNA is shown by a purple arrow. Red triangles indicate the positions of LoxP sites inserted into the conditional allele. (B) Kaplan-Meier plots of 9p21 locus homozygous (HOMO) deletion, 9p21 HOMO deletion encompassed (enco) and non-9p21 locus deletion–related WT in pediatric acute lymphoid leukemia (ALL). P value shows log-rank test result. (C) Graphical representation of the frequency of the of HET and HOMO 9p21 locus deletions enco in different human cancers. (D) Kaplan-Meier plots of patients with 9p21 deletions in total human cancers. P value shows log-rank test result. (E-F) Cre recombination of the targeted allele. Deleted allele was detected via genomic DNA PCR of BM cells from (E) R26CreER9p21fl/fl mice or (F) Prm-Cre–mediated 9p21+/− mice. (G) Mtap and Mllt3 expressions were confirmed via qRT-PCR. Symbols represent the populations including BM cells, spleen cells, B cells, and T cells from the same WT mouse or 9p21+/− mouse. (H) The haplodeficiency of Mtap, Cdkn2a, and Cdkn2b was demonstrated via bulk RNA-seq of cultured BM stromal cells. Symbols represent individual mice (WT mice, n = 4; 9p21+/− mice, n = 4). Data represent the mean ± standard deviation (SD). Statistical significance was defined using Mann-Whitney test. ∗P < .05 in panels G-H. C, carcinomas; N, neoplasms; ns, not significant; S, sarcomas; T, tumors.

Deletion of the 9p21 region in human cancers and genetic targeting of the 9p21s region in mice. (A) Schematic representation of the human 9p21 locus and the syntenic murine locus (9p21s). Genes and their 5′-3′ orientation are indicated by thick arrows (blue, green, and orange). A noncoding RNA is shown by a purple arrow. Red triangles indicate the positions of LoxP sites inserted into the conditional allele. (B) Kaplan-Meier plots of 9p21 locus homozygous (HOMO) deletion, 9p21 HOMO deletion encompassed (enco) and non-9p21 locus deletion–related WT in pediatric acute lymphoid leukemia (ALL). P value shows log-rank test result. (C) Graphical representation of the frequency of the of HET and HOMO 9p21 locus deletions enco in different human cancers. (D) Kaplan-Meier plots of patients with 9p21 deletions in total human cancers. P value shows log-rank test result. (E-F) Cre recombination of the targeted allele. Deleted allele was detected via genomic DNA PCR of BM cells from (E) R26CreER9p21fl/fl mice or (F) Prm-Cre–mediated 9p21+/− mice. (G) Mtap and Mllt3 expressions were confirmed via qRT-PCR. Symbols represent the populations including BM cells, spleen cells, B cells, and T cells from the same WT mouse or 9p21+/− mouse. (H) The haplodeficiency of Mtap, Cdkn2a, and Cdkn2b was demonstrated via bulk RNA-seq of cultured BM stromal cells. Symbols represent individual mice (WT mice, n = 4; 9p21+/− mice, n = 4). Data represent the mean ± standard deviation (SD). Statistical significance was defined using Mann-Whitney test. ∗P < .05 in panels G-H. C, carcinomas; N, neoplasms; ns, not significant; S, sarcomas; T, tumors.

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