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US 12,400,737 B2Granted
Methods of classifying diffuse large B-cell lymphoma
AssigneeCelgene Corporation
InventorsYixin Wang, Sarah Hersey, Fadi George Towfic, Alberto Risueno Perez
Life of this patent
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Abstract
A method of predicting if a subject has an Activated B Cell-like (ABC) subtype or a non-ABC subtype of Diffuse Large B-Cell Lymphoma (DLBCL), comprising (a) obtaining a sample from the subject; (b) measuring the expression levels of CD10, MUM1, FOXP1, and optionally Bcl-6; (c) determining a composite score based on the expression levels of CD10, MUM1, and FOXP1, and optionally Bcl-6; and (d) predicting if the subject has an ABC subtype or a non-ABC subtype of DLBCL based on the composite score.
Claims24
A method of predicting if a subject has an Activated B Cell-like (ABC) subtype of Diffuse Large B-Cell Lymphoma (DLBCL) or a non-ABC subtype of DLBCL comprising:
- (a) measuring the expression levels of biomarkers consisting of CD10, Bcl-6, MUM1, and FOXP1 in a sample from the subject;
- (b) determining a CD10 percentage being the percentage of the CD10 positively stained cells determined using an anti-CD10 antibody, a Bcl-6 percentage being the percentage of the Bcl-6 positively stained cells determined using an anti-Bcl-6 antibody, a MUM1 percentage being the percentage of the MUM1 positively stained cells determined using an anti-MUM1 antibody, and a FOXP1 percentage being the percentage of the FOXP1 positively stained cells determined by using an anti-FOXP1 antibody;
- (c) determining a composite score according to:
- the composite score=(−0.5×the CD10 percentage)+(−0.2×the Bcl-6 percentage)+(0.4×the MUM1 percentage)+(0.1×the FOXP1 percentage);
- (d) predicting if the subject has an ABC subtype or a non-ABC subtype of DLBCL based on the composite score;
- and
- (e) (i) administering to the subject predicted to have the ABC subtype of DLBCL a therapeutically effective amount of a treatment compound suitable for treating the ABC subtype of DLBCL, or (ii) administering to the subject predicted to have the non-ABC subtype of DLBCL a therapeutically effective amount of a treatment compound suitable for treating the non-ABC subtype of DLBCL.
4 more elements
A method of predicting if a subject has an Activated B Cell-like (ABC) subtype of Diffuse Large B-Cell Lymphoma (DLBCL) or a non-ABC subtype of DLBCL comprising:
- (a) measuring the expression levels of biomarkers consisting of CD10, Bcl-6, MUM1, and FOXP1 in a sample from the subject;
- (b) determining a CD10 percentage being the percentage of the CD10 positively stained cells determined using an anti-CD10 antibody, a Bcl-6 percentage being the percentage of the Bcl-6 positively stained cells determined using an anti-Bcl-6 antibody, a MUM1 percentage being the percentage of the MUM1 positively stained cells determined using an anti-MUM1 antibody, and a FOXP1 percentage being the percentage of the FOXP1 positively stained cells determined by using an anti-FOXP1 antibody;
- (c) determining a composite score according to:
- the composite score=(a CD10 weight×the CD10 percentage)+(a Bcl-6 weight×the Bcl-6 percentage)+(a MUM1 weight×the MUM1 percentage)+(a FOXP1 weight×the FOXP1 percentage);
- (d) predicting that the subject has the ABC subtype of DLBCL if the composite score is 8 or higher than 8, or predicting that the subject has the non-ABC subtype of DLBCL if the composite score is lower than 8;
- and
- (e) (i) administering to the subject predicted to have the ABC subtype of DLBCL a therapeutically effective amount of a treatment compound suitable for treating the ABC subtype of DLBCL, or (ii) administering to the subject predicted to have the non-ABC subtype of DLBCL a therapeutically effective amount of a treatment compound suitable for treating the non-ABC subtype of DLBCL.
4 more elements
A method of predicting if a subject has an Activated B Cell-like (ABC) subtype of Diffuse Large B-Cell Lymphoma (DLBCL) or a non-ABC subtype of DLBCL comprising:
- (a) measuring the expression levels of biomarkers consisting of CD10, MUM1, and FOXP1 in a sample from the subject;
- (b) determining a CD10 percentage being the percentage of the CD10 positively stained cells determined using an anti-CD10 antibody, a MUM1 percentage being the percentage of the MUM1 positively stained cells determined using an anti-MUM1 antibody, and a FOXP1 percentage being the percentage of the FOXP1 positively stained cells determined by using an anti-FOXP1 antibody;
- (c) determining a composite score according to:
- the composite score=(−1.4367173)+(−0.0238081×the CD10 percentage)+(0.01051371×the MUM1 percentage)+(0.02111138×the FOXP1 percentage);
- (d) predicting if the subject has an ABC subtype or a non-ABC subtype of DLBCL based on the composite score;
- and
- (e) (i) administering to the subject predicted to have the ABC subtype of DLBCL a therapeutically effective amount of a treatment compound suitable for treating the ABC subtype of DLBCL, or (ii) administering to the subject predicted to have the non-ABC subtype of DLBCL a therapeutically effective amount of a treatment compound suitable for treating the non-ABC subtype of DLBCL.
4 more elements
A method of predicting if a subject has an Activated B Cell-like (ABC) subtype of Diffuse Large B-Cell Lymphoma (DLBCL) or a non-ABC subtype of DLBCL comprising:
- (a) measuring the expression levels of biomarkers consisting of CD10, MUM1, and FOXP1 in a sample from the subject;
- (b) determining a CD10 percentage being the percentage of the CD10 positively stained cells determined using an anti-CD10 antibody, a MUM1 percentage being the percentage of the MUM1 positively stained cells determined using an anti-MUM1 antibody, and a FOXP1 percentage being the percentage of the FOXP1 positively stained cells determined by using an anti-FOXP1 antibody;
- (c) determining a composite score according to:
- the composite score=(a CD10 weight×the CD10 percentage)+(a MUM1 weight×the MUM1 percentage)+(a FOXP1 weight×the FOXP1 percentage);
- (d) predicting that the subject has the ABC subtype of DLBCL if the composite score is 0 or higher than 0, or predicting that the subject has the non-ABC subtype of DLBCL if the composite score is lower than 0;
- and
- (e) (i) administering to the subject predicted to have the ABC subtype of DLBCL a therapeutically effective amount of a treatment compound suitable for treating the ABC subtype of DLBCL, or (ii) administering to the subject predicted to have the non-ABC subtype of DLBCL a therapeutically effective amount of a treatment compound suitable for treating the non-ABC subtype of DLBCL.
4 more elements
Dependencies are inferred from the claim text.