The Society of Hematological Oncology (SOHO) held its annual meeting on September 8-11. The virtual format allowed for a dizzying number of presentations beginning with the twin “Meet the Professor” sessions on Wednesday. The concurrent tracks covered various hematological malignancies from acute myeloid leukemia (AML) to chronic lymphocytic leukemia (CLL), including sessions on cell therapies. Thankfully, all sessions were recorded.
In one “Meet the Professor” session, Koichi Takahashi of MD Anderson Cancer Center discussed single-cell profiling in AML. He gave an excellent analogy of bulk sequencing compared to single-cell sequencing as the former is akin to preparing a smoothie and the latter to understanding the exact proportion of individual components that make up the smoothie. He mentioned three papers that have utilized the Mission Bio Tapestri Platform to derive clonal level information (Morita and Takahashi, Nature Communications, Miles and Levine, Nature and Ediriwickema and Majeti, Blood Advances).
He then led a focused discussion on hit paper genotyping 150 bone marrow samples from 123 AML patients. This study led to the insight that the intracellular mutations that appear to co-occur in bulk analysis are mutually exclusive at the cellular level. In constructing clonal evolutionary phylogenetic trees, they found, approximately half of the lineages are linear while the other half are branched, which are then further subdivided by either a majority divergent pattern or a minority convergent pattern.
Dr. Takahashi then showed how the group is using multi-omics to analyze the genetic and phenotypic co-evolution to inform potential tipping points between the development of pre-leukemic and leukemic states. Lastly, his group is currently using Tapestri in clinical trials to track clonal level dynamics during AML treatment. With longitudinal samples, one can see which clones are present at diagnosis, which clones are eradicated by treatment, and which clones are emerging perhaps by selective pressure during treatment. By better understanding these processes and timing, new interventional strategies can be developed. Watch Dr. Takahashi’s recent webinar on his research.
The next “Meet the Professor” session in AML was presented by Sylvie Freeman of the University of Birmingham in the UK on “How Can We Improve on MRD Assessment by Flow Cytometry.” Similarly, Lori Muffly of Stanford University presented on detecting minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) and ways to optimize and innovate. Mission Bio is working with several groups actively performing research into this area by combining the level of specificity allowed with single-cell sequencing and cell surface protein expression to identify in which cell type MRD is present. Is it in the upstream part of the hematopoietic process or the fully developed cells? Is there an interventional strategy to be derived or timing associated with this information clinically?
As for the rest of the sessions, there were wonderful discussions on therapeutic and treatment advances that have been made or are currently in clinical trials for hematological malignancies. Some of the trials have been successful, but others have failed to show an improvement in PFS or OS and have been discontinued. In these cases, understanding the underlying mutations present in the patient population on a single-cell level might be advantageous to know if a subset of patients has a specific mutation that prevents the therapy from creating a complete response, a partial response, or no response at all.
To help answer these questions, Mission Bio has opened a Pharma Applications Development (PAD) lab specializing in working with pharmaceutical companies to develop assays capable of looking at SNVs, InDels, rearrangements, or copy number changes. Mission Bio offers a predesigned cell surface protein panel for hematological malignancies that identifies cell types in the hematopoietic differentiation cascade. Our PAD lab will also analyze the data and present insights to the pharmaceutical company in addition to designing the panel and performing the assay. This helps shorten the time to develop therapies by enabling companies to understand the true difference between the Kaplan Meier Curve populations. This is translational medicine occurring at the single-cell level.
During the conference, Mission Bio also announced two key improvements to the core capabilities of Tapestri intended to expand its accessibility and utility in the area of hematological malignancy research. These new additions to Tapestri enable researchers to apply single-cell analysis in a wider range of projects than previously possible by introducing new ready-to-use panels and a lowered input threshold. Learn more about the Tapestri update.