Determination of Immunoglobulin Gene Status in Lymphoid Cancers
Patent Number: Pending
Executive Summary:
General Description:
Chronic lymphocytic leukemia is the most common leukemia in adults and arises from a mature B cell with either mutated or unmutated immunoglobulin heavy chain transcripts, the latter having worse prognosis. Currently, the heavy chain mutation status is assessed by Sanger sequencing and comparing the transcript to known germ-line genes. The inventors demonstrate the heavy chain mutation status can be computed from unselected RNA-seq reads with results equal or superior to the clinical procedure. Therefore, a single RNA-seq assay can simultaneously yield gene expression profile, SNP and mutation information, as well as immunoglobulin heavy chain mutation status. This technology could eventually be used to personalize leukemia and lymphoma therapy and treatment based on the sequence of the immunoglobulin gene.
Future Directions:
Strengths:
Weaknesses:
Patent Status: Pending
Publications:
Blachly JS, Ruppert AS, Zhao W, Long S, Flynn J, Flinn I, Jones J, Maddocks K, Andritsos L, Ghia EM, Rassenti LZ, Kipps TJ, de la Chapelle A, Byrd JC. Immunoglobulin transcript sequence and somatic hypermutation computation from unselected RNA-seq reads in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2015 Apr 7;112(14):4322-7. doi: 10.1073/pnas.1503587112. Epub 2015 Mar 18. PubMed PMID: 25787252; PubMed Central PMCID: PMC4394264.
Inventor Bio: James Blachly
https://wexnermedical.osu.edu/find-a-doctor/james-blachly-md-43494
Executive Summary:
- Invention Type: Diagnostic
- Patent Status: Patent application pending
- Patent Link: https://tco.osu.edu/technology/determination-of-immunoglobulin-gene-status-in-lymphoid-cancers/
- Research Institute: Ohio State University
- Disease Focus: Leukemia and lymphoma
- Basis of Invention: High-throughput sequencing of RNA from leukemia cells isolated from patient bloodstream
- How it works: RNA-seq provides information about the mutation status of immunoglobulin heavy chain gene, which is essential for determination of the treatment strategy
- Inventors: James Blachly, John Byrd
- Development Stage: Validated on samples obtained from leukemia patients
- Novelty:
- RNA-seq analysis of leukemia cells transcriptome simultaneously provides immunoglobulin heavy chain status, gene expression profile and SNP information
- Clinical Applications:
- Chronic lymphocytic leukemia classification
- Lymphoma classification
General Description:
Chronic lymphocytic leukemia is the most common leukemia in adults and arises from a mature B cell with either mutated or unmutated immunoglobulin heavy chain transcripts, the latter having worse prognosis. Currently, the heavy chain mutation status is assessed by Sanger sequencing and comparing the transcript to known germ-line genes. The inventors demonstrate the heavy chain mutation status can be computed from unselected RNA-seq reads with results equal or superior to the clinical procedure. Therefore, a single RNA-seq assay can simultaneously yield gene expression profile, SNP and mutation information, as well as immunoglobulin heavy chain mutation status. This technology could eventually be used to personalize leukemia and lymphoma therapy and treatment based on the sequence of the immunoglobulin gene.
Future Directions:
- Clinical trials
Strengths:
- Reliable compared to the existing technique
- Provides more clinically relevant information than the current test
Weaknesses:
- Relatively small patient sample
- Validated in patients with advanced disease
Patent Status: Pending
Publications:
Blachly JS, Ruppert AS, Zhao W, Long S, Flynn J, Flinn I, Jones J, Maddocks K, Andritsos L, Ghia EM, Rassenti LZ, Kipps TJ, de la Chapelle A, Byrd JC. Immunoglobulin transcript sequence and somatic hypermutation computation from unselected RNA-seq reads in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2015 Apr 7;112(14):4322-7. doi: 10.1073/pnas.1503587112. Epub 2015 Mar 18. PubMed PMID: 25787252; PubMed Central PMCID: PMC4394264.
Inventor Bio: James Blachly
https://wexnermedical.osu.edu/find-a-doctor/james-blachly-md-43494
