Diagnosis of lymphoid malignancies and minimal residual disease detection


Ontology type: sgo:Patent     


Patent Info

DATE

N/A

AUTHORS

Anna M. Sherwood , Harlan S. Robins

ABSTRACT

Methods are described for diagnosis of a lymphoid hematological malignancy in a subject prior to treatment, and for detecting minimal residual disease (MRD) in the subject after treatment for the malignancy, by high throughput quantitative sequencing (HTS) of multiple unique adaptive immune receptor (TCR or Ig) encoding DNA molecules that have been amplified from DNA isolated from blood samples or other lymphoid cell-containing samples. Amplification employs oligonucleotide primer sets designed to amplify CDR3-encoding sequences within substantially all possible human VDJ or VJ combinations. Disease-characteristic adaptive immune receptor clonotypes occur, prior to treatment, at a relative frequency of at least 15-30% of rearranged receptor CDR3-encoding gene regions. Following treatment, persistence of at least one such clonotype at a detectable frequency of at least 10−6 or at least 10−5 receptor CDR3-encoding regions indicates MRD. Improved quantitative embodiments are provided by inclusion of a template composition for amplification factor determination and related methods. More... »

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    401 schema:description <p id="p-0001" num="0000">Methods are described for diagnosis of a lymphoid hematological malignancy in a subject prior to treatment, and for detecting minimal residual disease (MRD) in the subject after treatment for the malignancy, by high throughput quantitative sequencing (HTS) of multiple unique adaptive immune receptor (TCR or Ig) encoding DNA molecules that have been amplified from DNA isolated from blood samples or other lymphoid cell-containing samples. Amplification employs oligonucleotide primer sets designed to amplify CDR3-encoding sequences within substantially all possible human VDJ or VJ combinations. Disease-characteristic adaptive immune receptor clonotypes occur, prior to treatment, at a relative frequency of at least 15-30% of rearranged receptor CDR3-encoding gene regions. Following treatment, persistence of at least one such clonotype at a detectable frequency of at least 10<sup>&#8722;6 </sup>or at least 10<sup>&#8722;5 </sup>receptor CDR3-encoding regions indicates MRD. Improved quantitative embodiments are provided by inclusion of a template composition for amplification factor determination and related methods.</p>
    402 schema:keywords DNA
    403 DNA molecule
    404 Residual Neoplasm
    405 TCR
    406 amplification
    407 blood sample
    408 clonotypes
    409 composition
    410 diagnosis
    411 disease characteristic
    412 disease detection
    413 embodiment
    414 frequency
    415 gene region
    416 high throughput
    417 human
    418 immune receptor
    419 inclusion
    420 lymphoid malignancy
    421 malignancy
    422 method
    423 oligonucleotide primer
    424 persistence
    425 receptor
    426 related method
    427 relative frequency
    428 sample
    429 sequence
    430 schema:name Diagnosis of lymphoid malignancies and minimal residual disease detection
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