April 25, 2018
Sponsored by

A High-Sensitivity, Clone-Specific Strategy to Evaluate Minimal Residual Disease in AML


Professor, Hematology, Medical School of Sorbonne University, Paris; Head of the Hematology Laboratory, Saint-Antoine Hospital 

This webinar will share details from a study at the Saint-Antoine Research Center, Sorbonne University to test the feasibility of a high-sensitivity, clone-specific strategy for evaluating minimal residual disease (MRD) in acute myeloid leukemia (AML).

AML is a genetically heterogeneous group of blood malignancies. Some specific translocations or mutations, such as t(8;21), inv(16), or NPM1 mutations, can serve as markers of treatment response, or detection of MRD. However, most AMLs harbor several mutations ordered in time to form the founding clone and subsequent linear or branching subclones. Improving the tools for a clone-specific, multi-target detection of MRD may be of particular importance in the future.

In this webinar, François Delhommeau, of Saint-Antoine Research Center will discuss a research study to test such a strategy in a retrospective cohort of 69 AML cases. Delhommeau and colleagues established the clonal architecture of each AML using standard cytogenetic and molecular assays, as well as targeted next generation sequencing (NGS). From this, they designed a clone-specific strategy based on fluorescent in situ hybridization (FISH) and high-sensitivity NGS (Haloplex HS) to detect chromosomal aberrations and mutations, respectively, in follow-up samples.

The combination of these techniques allowed the team to track chromosomal and genomic lesions down to 0.5% of the cell population in follow-up samples. By using these techniques, they found that 65 out of 69 cases were evaluable at several time points of follow up. Moreover, they observed that initiating events, such as DNMT3A or TET2 mutations, often persist, and appear not to be appropriate markers to predict short term relapse when considered in isolation from other factors. In contrast, the persistence of several lesions in more than 0.4% of the cells from remission samples may be predictive of lower leukemia-free and overall survivals.

Although larger prospective studies are needed to confirm these results, the data that Dr. Delhommeau will share show that a multi-target, clone-specific, minimal residual disease follow-up strategy may be feasible in the vast majority of AML cases.


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