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US 11,692,228 B2Granted
Gene expression profiles for B-cell lymphoma and uses thereof
AssigneeProvincial Health Services Authority
InventorsDaisuke Ennishi, Aixiang Jiang, Ryan Morin, David Scott
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Abstract
The present invention relates to gene expression profiles for B-cell lymphoma. More specifically, the present invention relates to gene expression profiles for diagnosis, prognosis or therapy selection for an aggressive B-cell lymphoma.
Claims17
A method for administering a therapy for a subject with an aggressive B-cell lymphoma comprising:
- determining the molecular subgroup of the aggressive B-cell lymphoma by preparing a gene expression profile from a biopsy obtained from the subject, the gene expression profile covering all of the following genes:
- AFMID, ALOX5, BATF, CD24, CD80, CDK5R1, EBI3, GAMT, GPR137B, IL21R, IRF4, JCHAIN, LY75, MIR155HG, MYC, OR13A1, PEG10, QRSL1, RFFL, RGCC, SEMA7A, SGPP2, SLC25A27, SMIM14, SNHG19, STAT3, SYBU, TNFSF8, VASP, and VOPP1, the gene expression profile being determined based on a level of a nucleic acid encoded by the gene;
- determining that the molecular subgroup of the aggressive B-cell lymphoma is a positive double hit signature (DHITsig-pos) lymphoma based upon detecting that:
- collectively OR13A1, MYC, SLC25A27, ALOX5, TNFSF8, PEG10, GAMT, SNHG19, QRSL1, RGCC, JCHAIN, CD24, AFMID, SMIM14, and SYBU are overexpressed in the biopsy;
- and
- collectively GPR137B, CDK5R1, LY75, VASP, RFFL, MIR155HG, VOPP1, BATF, STAT3, IRF4, SGPP2, CD80, SEMA7A, EBI3, and IL21R are underexpressed in the biopsy;
- and
- administering to the subject determined to have the DHITsig-pos lymphoma one or more of:
- dose intensive immunochemotherapy, a cell-based therapy, CAR T-cell therapy, a BCL2 inhibitor, an enhancer of zeste homolog 2 (EZH2 inhibitor), a histone deacetylase inhibitor, an arachidonate 5-lipoxygenase inhibitor, a Bruton's tyrosine kinase inhibitor, ibrutinib, a PIM kinase inhibitor, SGI-1776, belinostat, vorinostat, a PI3K inhibitor, copanlisib, buparlisib, a protein kinase C inhibitor, sotrastaurin, immunomodulatory drugs, lenalidomide, or an anti-CD20 antibody.
6 more elements
A method for administering a therapy for a subject with an aggressive B-cell lymphoma comprising:
- determining the molecular subgroup of the aggressive B-cell lymphoma by preparing a gene expression profile from a biopsy obtained from the subject, the gene expression profile covering all of the following genes:
- AFMID, ALOX5, BATF, CD24, CD80, CDK5R1, EBI3, GAMT, GPR137B, IL21R, IRF4, JCHAIN, LY75, MIR155HG, MYC, OR13A1, PEG10, QRSL1, RFFL, RGCC, SEMA7A, SGPP2, SLC25A27, SMIM14, SNHG19, STAT3, SYBU, TNFSF8, VASP, and VOPP1, the gene expression profile being determined based on a level of a nucleic acid encoded by the gene;
- determining that the molecular subgroup of the aggressive B-cell lymphoma is a negative double hit signature (DHITsig-neg) lymphoma based upon detecting that:
- collectively OR13A1, MYC, SLC25A27, ALOX5, TNFSF8, PEG10, GAMT, SNHG19, QRSL1, RGCC, JCHAIN, CD24, AFMID, SMIM14, and SYBU are underexpressed in the biopsy;
- and
- collectively GPR137B, CDK5R1, LY75, VASP, RFFL, MIR155HG, VOPP1, BATF, STAT3, IRF4, SGPP2, CD80, SEMA7A, EBI3, and IL21R are overexpressed in the biopsy;
- and
- administering to the subject determined to have the DHITsig-neg lymphoma rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisone (R-CHOP).
5 more elements
A method for determining a prognosis for a subject with an aggressive B-cell lymphoma comprising:
- determining the molecular subgroup of the aggressive B-cell lymphoma by preparing a gene expression profile from a biopsy obtained from the subject, the gene expression profile covering all of the following genes:
- AFMID, ALOX5, BATF, CD24, CD80, CDK5R1, EBI3, GAMT, GPR137B, IL21R, IRF4, JCHAIN, LY75, MIR155HG, MYC, OR13A1, PEG10, QRSL1, RFFL, RGCC, SEMA7A, SGPP2, SLC25A27, SMIM14, SNHG19, STAT3, SYBU, TNFSF8, VASP, and VOPP1;
- wherein the molecular subgroup is a positive double hit signature (DHITsig-pos) if:
- collectively OR13A1, MYC, SLC25A27, ALOX5, TNFSF8, PEG10, GAMT, SNHG19, QRSL1, RGCC, JCHAIN, CD24, AFMID, SMIM14, and SYBU are overexpressed in the biopsy;
- and
- collectively GPR137B, CDK5R1, LY75, VASP, RFFL, MIR155HG, VOPP1, BATF, STAT3, IRF4, SGPP2, CD80, SEMA7A, EBI3, and IL21R are underexpressed in the biopsy;
- and wherein the molecular subgroup is a negative double hit signature (DHITsig-neg) if:
- collectively OR13A1, MYC, SLC25A27, ALOX5, TNFSF8, PEG10, GAMT, SNHG19, QRSL1, RGCC, JCHAIN, CD24, AFMID, SMIM14, and SYBU are underexpressed in the biopsy;
- and
- collectively GPR137B, CDK5R1, LY75, VASP, RFFL, MIR155HG, VOPP1, BATF, STAT3, IRF4, SGPP2, CD80, SEMA7A, EBI3, and IL21R are overexpressed in the biopsy;
- wherein preparing the gene expression profile comprises using a plurality of DNA probes, a plurality of subsets of the plurality of probes having a nucleic acid sequence of a corresponding one of each of SEQ ID NO:1 through SEQ ID NO:30;
- wherein a DHITsig-pos molecular subgroup is predictive of a poor prognosis and a DHITsig-neg molecular subgroup is predictive of a good prognosis.
9 more elements
Dependencies are inferred from the claim text.