CRISPR loss-of-function screening of recurrently mutated genes in DLBCL. (A) Schematic representation of CRISPR loss-of-function screening targeting 86 recurrently mutated genes in DLBCL. (B) Overlap of sgRNA-targeted genes with recurrently altered TSGs in B-ALL/LBL, and PTCL, NOS. Because of interspecies differences, 86 murine genes in the CRISPR library correspond to 84 orthologous human genes. (C) Survival curves of recipient mice transplanted with HSPCs transduced with mock plasmid (n = 6) or the CRISPR library (n = 199). Log-rank test. (D) Distribution of hematologic malignancies in recipient mice (n = 132) according to the Bethesda proposals. (E) Landscape of significantly recurrent (q < 0.01) sgRNA-mediated disruption in the entire cohort (n = 104). Disease type, involved organ, and CRISPR library pool (bottom) as well as q values (right) are shown. (F-K) Number of samples harboring sgRNAs for each gene in the entire cohort (F; n = 104), B-cell lymphoma (G; n = 20), B-ALL/LBL (H; n = 19), T-cell lymphoma (I; n = 24), T-ALL/LBL (J; n = 15), and AML (K; n = 20). Significantly recurrent genes (q < 0.01) are colored and marked with asterisks. AML, acute myeloid leukemia; AUL, acute undifferentiated leukemia; NGS, next-generation sequencing; NK-lymphoma, natural killer-cell lymphoma; PTCL NOS, peripheral T-cell lymphoma, not otherwise specified; TSGs, tumor suppressor genes.
Figure 1.

CRISPR loss-of-function screening of recurrently mutated genes in DLBCL. (A) Schematic representation of CRISPR loss-of-function screening targeting 86 recurrently mutated genes in DLBCL. (B) Overlap of sgRNA-targeted genes with recurrently altered TSGs in B-ALL/LBL, and PTCL, NOS. Because of interspecies differences, 86 murine genes in the CRISPR library correspond to 84 orthologous human genes. (C) Survival curves of recipient mice transplanted with HSPCs transduced with mock plasmid (n = 6) or the CRISPR library (n = 199). Log-rank test. (D) Distribution of hematologic malignancies in recipient mice (n = 132) according to the Bethesda proposals. (E) Landscape of significantly recurrent (q < 0.01) sgRNA-mediated disruption in the entire cohort (n = 104). Disease type, involved organ, and CRISPR library pool (bottom) as well as q values (right) are shown. (F-K) Number of samples harboring sgRNAs for each gene in the entire cohort (F; n = 104), B-cell lymphoma (G; n = 20), B-ALL/LBL (H; n = 19), T-cell lymphoma (I; n = 24), T-ALL/LBL (J; n = 15), and AML (K; n = 20). Significantly recurrent genes (q < 0.01) are colored and marked with asterisks. AML, acute myeloid leukemia; AUL, acute undifferentiated leukemia; NGS, next-generation sequencing; NK-lymphoma, natural killer-cell lymphoma; PTCL NOS, peripheral T-cell lymphoma, not otherwise specified; TSGs, tumor suppressor genes.

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