Omics and artificial intelligence integration for stratifying blast crisis CML using COSMIC signatures and pan-cancer precision drug repurposing

Figure 1 Flowchart summarizing the integrated experimental and computational pipeline used in this study. ANOVA: Analysis of variance; BC-CML: Blast crisis chronic myeloid leukemia; COSMIC: Catalogue of Somatic Mutations in Cancer; DS: DrugScore; GATK: Genome Analysis Toolkit; GScore: GeneScore; NMF: Non-negative matrix factorization; PCA: Principal component analysis; VEP: Variant Effect Predictor.

Figure 2 Mutation frequencies in accelerated-phase chronic myeloid leukemia and blast crisis chronic myeloid leukemia patient samples. ACIN1: Apoptotic chromatin condensation inducer 1; AP-CML: Accelerated-phase chronic myeloid leukemia; BC-CML: Blast crisis chronic myeloid leukemia; BCR: Breakpoint cluster region; BRCA: Breast cancer susceptibility gene; EGFR: Epidermal growth factor receptor; ERG: ETS-related gene; NDRG2: N-myc downstream-regulated gene 2; NF1: Neurofibromatosis type 1; RPTOR: Regulatory associated protein of mechanistic target of rapamycin complex 1; STAB1: Stabilin 1.

Figure 3 Distribution of somatic mutation types in blast crisis chronic myeloid leukemia samples. BC-CML: Blast crisis chronic myeloid leukemia.

Figure 4  Mutation frequency across top chromosomes involved in blast crisis chronic myeloid leukemia samples.

Figure 5 Integrated analysis of type of mutations, their frequencies in accelerated-phase myeloid leukemia, initial/blast crisis chronic myeloid leukemia, initial association with type of cancer and relevant Food and Drug Administration-approved drug for repurposing. AML: Acute myeloid leukemia; AP-CML: Accelerated-phase myeloid leukemia, initial; APR-246: Eprenetapopt; BC-CML: Blast crisis chronic myeloid leukemia; BCL2: B-cell lymphoma 2; BRCA: Breast cancer susceptibility gene; CBL: Casitas B-cell lineage; CLL: Chronic lymphocytic leukemia; DNMT3A: DNA (cytosine-5)-methyltransferase 3 A; EGFR: Epidermal growth factor receptor; JAK: Janus kinase; MDS: Myelodysplastic syndrome; MPN: Myeloproliferative neoplasms; NPM1: Nucleophosmin 1; NSCLC: Non-small-cell lung cancer; PV: Polycythemia vera.