Proteomics and NGS Analysis of Induced Myeloid Leukemia Cells

Abstract

Abstract: Induced myeloid leukemia cells have emerged as critical models for unraveling intricate molecular mechanisms of leukemogenesis. Integration of proteomics and Next-Generation Sequencing (NGS) analyses has yielded profound insights. Mcl1's significance in tumorigenesis and therapeutic resistance highlights Mcl-1 inhibitors' promise as anticancer agents. A selectively designed macrocyclic compound for Mcl-1 with high affinity, currently in clinical development, signifies a milestone in precision therapy. Activation of the Bak-dependent mitochondrial apoptotic pathway in acute myeloid leukemia offers novel insights into apoptotic regulation and potential interventions. Strikingly, complete tumor regression was achieved in diverse myeloma and acute myeloid leukemia models with a single tolerated dose of the compound, as monotherapy or combined with bortezomib or venetoclax, showcasing its therapeutic potential. Structural analyses through PyMOL and RasMol reveal intricate protein architecture, informing amino acid distributions, topology, and electrostatic profiles. These insights underpin understanding of protein functionality and intermolecular interactions. Simultaneously, multi-omics strategies, spanning genomics, epigenomics, transcriptomics, and proteomics, illuminate induced myeloid leukemia cells. These approaches uncover recurrent mutations, copy number variations, and fusion genes driving leukemogenesis. Epigenetic modifications, notably DNA methylation and chromatin remodeling, modulate gene expression in leukemic contexts.Together, these efforts underscore the significance of integrating diverse omics layers to decode leukemic transformation intricacies. The findings offer therapeutic prospects and insights into disease progression, fostering nuanced treatments across oncogenic landscapes beyond myeloid leukemia.