617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Dissecting AML heterogeneity to refine treatment approaches
Andy G.X. Zeng, Amanda Mitchell, Oleksandr Galkin, et al.
Authors Conclusion from the Abstract: Our data establish that scRNA-seq informed deconvolution of bulk expression data permits characterization of the cellular hierarchy of individual AML patients. This framework can enhance our understanding of many aspects of biological, genomic, and clinical heterogeneity in AML, and represents a powerful tool to enable personalized therapeutic decision-making in AML.
Benjamin J. Huang, Jenny L. Smith, Rhonda E. Ries, et al.
Authors Conclusion from the Abstract: This study demonstrates that a 54 LSC gene expression panel can enhance the predictive power of conventional cytomolecular markers and can more effectively partition patients into risk groups.
Hussein A Abbas, Dapeng Hao, Katarzyna Tomczak, et al.
Authors Conclusion from the Abstract: This is one of the first studies examining the effect of PD-1 blockade at single cell resolution in a hematologic malignancy. Further, this is the largest single study analyzing single AML cells longitudinally. AML cells harboring deletion 7/7q loss, enriched for LSC signature and metabolic/oxidative pathways, were features associated with resistance to azacitidine/nivolumab therapy. Azacitidine/nivolumab induced novel and expanded T cell clonotypes primarily in responders. Disentangling AML cells from their complex microenvironment revealed characteristics that shaped resistance to ICB-based therapy and could inform strategies to target AML vulnerabilities.
Suruchi Pacharne, Oliver M. Dovey, Jonathan L Cooper, et al.
Authors Conclusion from the Abstract: Collectively our study: i) identifies SETBP1overexpression as a non-genetic alteration driving a subgroup of FLT3-ITD mutant AMLs lacking class-defining somatic mutations and ii) goes on to define the genetic vulnerabilities of such AMLs as a starting point for the development of targeted therapies.
Gail J. Roboz, Farhad Ravandi, Andrew H Wei, et al.
Authors Conclusion from the Abstract: The QUAZAR AML-001 Maintenance Trial was the first prospective, randomized trial to include long-term longitudinal assessment of MRD in older patients with AML in remission. In both treatment arms, MRD+ status (≥ 0.1%) after induction ± consolidation was associated with significantly shorter OS and RFS compared with MRD– status. Approximately one-fourth of MRD responders treated with CC-486 achieved MRD negativity > 6 mo after study entry, suggesting that CC-486 could induce MRD negativity after prolonged MRD+ status. Maintenance Tx with CC-486 substantially improved OS and RFS independent of MRD status at BL.
Kunhwa Kim, Abhishek Maiti, Tapan M. Kadia, et al.
Authors Conclusion from the Abstract: TP53mut is associated with inferior response with shorter response duration, higher MRD positivity and inferior survival outcomes in pts with AML receiving frontline therapy with VEN and DEC. Novel therapies are needed to overcome TP53-mediated resistance to VEN with hypomethylating agents in AML.