AML MutationCounter a tool to detect residual and recurrent leukemia

Abstract AsystBio LLC proposes to market a molecular tool kit called AML MutationCounter to count somatic mutations in genes that contribute to the development of acute myeloid leukemia AML We have developed a set of reagents and computer programs for application of next generation sequencing to count AML gene mutations The tool kit is versatile and can be used with either of the two major DNA sequencing platforms Illumina Hi Seq and ThermoFisher Ion Proton Every year AML afflicts Americans with nearly dying from the disease Many patients respond to primary therapy and achieve clinical remission Remission is currently determined by a reduction of leukemic blasts in bone marrow to andlt of cells A more sensitive and specific test for remission may guide clinicians to achieve more durable remission and improve stratification of patients for likelihood of relapse One recent study found that forty eight percent of patients in remission retained AML gene mutations in andgt of marrow or blood cells and these patients survival was on average of that seen in patients who cleared mutations to andlt during remission Thus the presence or absence of residual disease at remission is highly prognostic Patients who receive a bone marrow transplant after remission sometimes display emerging clones of host bone marrow termed bone marrow chimerism It is important to determine whether these emerging clones represent recurrent leukemia as early as possible to implement salvage therapies Our advisory panel of oncologists at the University of North Carolina and NC Memorial Hospital expresses enthusiasm for a sensitive accurate rapid and low cost test for residual and recurrent leukemia Studies in this Phase I STTR grant application will involve a collaboration between AsystBio LLC and the University of North Carolina at Chapel Hill to produce a molecular tool kit for measurement of AML associated somatic gene mutations in bone marrow specimens Studies in Aim will establish the accuracy sensitivity and reproducibility of the kit for quantification of mutant allele frequencies using simulated data and a standard reference cell line Studies in Aim will apply the tool kit to patient samples that were collected at the time of remission before a subsequent recurrence of leukemia Samples are selected to include the NPM leukemia driver gene mutation in the primary cancer The presence of mutations in NPM in remission samples is a poor prognostic sign We will show that our kit detects mutations in NPM and other AML associated genes at remission in patients that were destined to relapse This phase I project demonstrates the feasibility of AML MutationCounter for detection of minimal residual and recurrent disease in AML Our phase II commercialization plan will include a clinical trial to establish the utility of the test kit as well as active marketing of the test kit to academic medical centers and commercial test laboratories Project Narrative AsystBio LLC will produce a molecular tool kit that combines existing next generation DNA sequencing technology with AsystBio s proprietary computer programs for sensitive detection of AML associated gene mutations The ability to detect residual or recurrent tumor cells results in better guidance in the clinic for when to continue or cease induction therapy when to transplant and when mutations are actionable for use of targeted therapies