617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Single Cell Profiling and Novel molecular Markers
Beena E Thomas, Pruthvi Perumalla, Swati S Bhasin, et al.
Authors Conclusion from the Abstract: Using single-cell transcriptomics we developed a novel potential gene signature to characterize heterogeneous AML blast populations with high sensitivity. These genes and the pathways they regulate implicate potential therapeutic targets in pediatric AML. Single-cell transcriptome analysis also enabled the identification of cell clusters with modulated gene expression at both Dx and EOI that may be useful in predicting relapse/remission.
Shuting Jiang, Fuhong He, Li Gao, et al.
Authors Conclusion from the Abstract: Taken together, these data showed that pediatric AMLs represented heterogeneous populations at both diagnosis and remission. Among the residual tumor clusters that survived chemotherapy, a small fraction (6/18) were HSC/MPP-like, LMPP-like and cDC-like cells with known chemo-resistant expression features. These findings provide the first in vivo characterization of cellular heterogeneity in chemo-treated pAML with complete remission. Further studies are needed to determine the molecular characteristics of these residual cells that may convey chemo-resistance and to determine whether the presence of these cells is associated with an increased risk of relapse.
Muharrem Muftuoglu, Zoe Alaniz, Duncan Mak, et al.
Authors Conclusion from the Abstract: Single-cell profiling of R/R AML using CyTOF reveals significantly heterogeneous expression patterns of molecules targeted by BH3 mimetics (Bcl-2 and Mcl-1), CAR T-cells, and other antibody-based immunotherapeutic therapies. This approach provides a rationale to develop combinatorial therapeutic approaches targeting distinct leukemia sub-populations with discrete expression patterns of established and novel putative targets. An example is the combined targeting of Bcl-2 and Mcl-1, which are differentially expressed in early and more differentiated leukemia subpopulations.
Jayakumar Vadakekolathu, Tung On Yau, Heidi Altmann, et al.
Authors Conclusion from the Abstract: Patients with immune-infiltrated AML exhibit features of IES, which may correlate with adverse-risk molecular features, chemotherapy refractoriness and shorter survival. Molecular circuits reflective of IES might also underpin AML relapse after conventional induction chemotherapy. IES T cells could be functionally rejuvenated by novel immunotherapies being investigated in AML.
Hassan Awada, Arda Durmaz, Carmel Gurnari, et al.
Authors Conclusion from the Abstract: The heterogeneity inherent in the genomic changes across nearly 7000 AML patients is too vast for traditional prediction methods. Using newer ML methods, however, we were able to decipher a set of prognostic subgroups predictive of survival, allowing us to move AML into the era of personalized medicine.
Hidemasa Matsuo, Kenichi Yoshida, Kana Nakatani, et al.
Authors Conclusion from the Abstract: These results suggest that mutations in MLL-rearranged AML are associated with MLL fusion partners, and KRASmutations frequently coexist with high-risk MLL fusions. KRAS mutations are distinct adverse prognostic factors in MLL-r AML, regardless of risk subgroup, therefore, potentially useful for accurate treatment stratification.