| Abstract |
Multiple Myeloma (MM) is an incurable plasma cell dyscrasia characterized
by recurrent translocations into immunoglobulin loci and a unique V(D)J
rearrangement signature that can be used to track disease over time.
Modern myeloma therapy results in high response rates, however the
majority of patients still relapse, suggesting persistence of minimal
residual disease (MRD) beyond current limits of detection. We developed a
targeted-capture approach to detect V(D)J rearrangements and recurrent
immunoglobulin translocations to enable MRD assessment. We validated this
assay in 69 human myeloma cell lines and established a limit of detection
of 1/1000 DNA fragments. Our methods agree with MRD measured by multi-
parameter flow cytometry in 11/14 patient samples. One sample was MRD
positive by MFC and negative by targeted-capture sequencing, two were
positive by sequencing and negative by MFC. Targeted capture sequencing is
an alternative strategy to MRD detection and has potential applications
for disease monitoring and immune repertoire profiling.
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