The Specific Aim of the Molecular Diagnostics Core is to support Projects by performing assays integral to the completion of their Specific Aims. Specifically, for Project 2 we will perform FLT3-ITD allelic ratio to define eligibility for Protocol #2487, as well as testing for FLT3-ITD allelic ratio. FLT3 and cKIT mutation studies in paired diagnostic and relapse samples, per protocol requirements. For the CAL101 trial, we will use IgH VDJ rearrangements to monitor disease burden as a measure of response. For Project 3. we will perform WTl expression studies for protocol #2498. on samples taken before, during, and at relapse, using flow cytometry to isolate AML blasts (via Core A). In addition, select samples will have single cell analyses performed to note the heterogeneity of WTl expression. Lastly, for protocol #2495 in Project 4, we will perform IgH VDJ and RORI expression to monitor disease burden and response, and perform gene expression analyses on pre- and relapsed samples to investigate pathways associated with resistance. These assays are integral to the aims of these protocols, and the assays are not available in commercial laboratories. The Radich Lab is a CAP/CLIA certified laboratory involved in studying the molecular genetics of leukemia and devising clinically useful tests more molecular diagnostics and monitoring. The lab has serviced as the North American molecular core for -10 CML industry trials, as well as the core of SWOG trials in ALL, CML, and AML, and as the central molecular core for the last and current COG AML trial, as well as establishing collaborations with biotechnology to develop new platforms for molecular diagnostics Cepheid, Fluidigm, and Nanostring.

Public Health Relevance

Molecular diagnostics are an important tool in understanding the biology of response, as well as providing an important and powerful tool in disease monitoring. The activities of Core B will help investigators more accurately measure the effectiveness of their therapeutic interventions, as well as help understand which patients become resistant to therapy, and why.

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National Cancer Institute (NCI)
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Fred Hutchinson Cancer Research Center
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