Fig. 5: FL-derived CRISPRMLL-AF4+ ALL specifically recapitulates the molecular profile of MLL-AF4 infant-ALL. | Nature Communications

Fig. 5: FL-derived CRISPRMLL-AF4+ ALL specifically recapitulates the molecular profile of MLL-AF4 infant-ALL.

From: A human fetal liver-derived infant MLL-AF4 acute lymphoblastic leukemia model reveals a distinct fetal gene expression program

Fig. 5

a UMAP showing clustering of CRISPRMLL-AF4+ ALL (light green; black border = proB ALL, no border = preB ALL), MLL-AF4 infant-ALL (iALL (dark green), n = 19), MLL-AF4 childhood-ALL (chALL (orange), n = 5)20, and CB MLL-Af4+ ALL35 (yellow, n = 6) based on a set of genes differentially expressed in both FL (compared to ABM) and MLL-AF4 infant-ALL (compared to MLL-AF4 childhood-ALL) (139 genes; Supplementary Data 2). b Gene set enrichment analyses (GSEA)52 showing CRISPRMLL-AF4+ ALL is significantly more enriched for genes upregulated in MLL-AF4 infant-ALL (compared to MLL-AF4 childhood-ALL) (617 genes, p < 0.03) and in FL (compared to ABM) (5709 genes, p < 0.001) when compared to CB MLL-Af4+ ALL. c Box-and-whisker plots showing MLL-AF4 enrichment (MLL-N ChIP-seq reads/bp normalized to 107 total reads) for CRISPRMLL-AF4+ ALL and CB MLL-Af4+ ALL (FLAG ChIP-seq) at infant-ALL-specific genes (193 genes, two-tailed Mann–Whitney test, p = 0.012) and FL-specific genes (3949 genes, two-tailed Mann–Whitney test, p < 0.0001). Data are shown as mean ± SEM. Source data are provided as a Source Data file. d (left) Barplot showing expression of IGF2BP1 in MLL-AF4 childhood-ALL (chALL (orange), n = 5)20, CB MLL-Af4+ ALL (yellow, n = 6)35, MLL-AF4 infant-ALL (iALL (dark green), n = 19)20 and CRISPRMLL-AF4 + ALL (light green; black border = proB ALL, no border = preB ALL). Data shown as mean ± SEM. Source data are provided as a Source Data file. (Right) MLL-Af4 (FLAG ChIP-seq) in CB MLL-Af4+ ALL, MLL-N, and AF4-C ChIP-seq in CRISPRMLL-AF4+ ALL and H3K79me2 ChIP-seq in CRISPRMLL-AF4+ ALL and matched unedited FL sample at IGF2BP1. ChIP-seq data shown are normalized to 107 total reads. e (left) Barplot showing expression of HOXB4 in MLL-AF4 childhood-ALL (chALL (orange), n = 5)20, CB MLL-Af4+ ALL (yellow, n = 6)35, MLL-AF4 infant-ALL (iALL (dark green), n = 19)20, and CRISPRMLL-AF4+ ALL (light green; black border = proB ALL, no border = preB ALL). Data are shown as mean ± SEM. Source data are provided as a Source Data file. (Right) MLL-Af4 (FLAG ChIP-seq) in CB MLL-Af4+ ALL, MLL-N, and AF4-C ChIP-seq in CRISPRMLL-AF4+ ALL and H3K79me2 ChIP-seq in CRISPRMLL-AF4+ ALL and matched unedited FL sample at HOXB3/HOXB4. ChIP-seq data shown are normalized to 107 total reads.

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