1568 Single-Cell Multi-Omic Analysis of AML MRD Reveals Differences in Clonal Architecture

The Mission Bio AML single-cell MRD assay quantitatively characterizes SNVs and surface protein expression simultaneously across thousands of individual cells. In contrast, bulk NGS requires averaging across the entire population, preventing co-localization of joint genetic lesions or changes in cellular immunophenotype, and leukemia-associated immunophenotyping by flow cytometry can miss residual AML cells that have the same genotype, but different immunophenotype from the diagnostic population. These methods are commonly discordant, leading to clinical questions for individual surveillance and treatment. Combining these assays with single-cell resolution overcomes these limitations and reveals subclonal populations that may harbor resistance mutations or unique therapeutic targets.
After demultiplexing three independent patient samples per Tapestri machine cycle, we analyzed several thousand cells/sample. As expected, residual disease was identified in MRD+, relapse+ samples and was not identified in MRD-, relapse- samples. For the MRD-, relapse+ cases, we identified MRD in 2/6 cases; with the remaining 4 cases having reported disease present below our assay’s limit of detection of 10-4. Of the 5 MRD+, relapse- cases, 3 had residual cells with the AML genotype where the remaining 2 did not. Of note, cases that relapsed generally had a more branched clonal architecture at diagnosis than cases that did not relapse, regardless of flow results.

Read more