Methods of stratifying patients for treatment with retinoic acid receptor-α agonists
AssigneeSyros Pharmaceuticals, Inc.
InventorsMichael Robert McKeown, Christopher Fiore, Matthew Lucas Eaton, Emily Payton Lee, Christian Fritz
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Abstract
Described herein are methods that define cellular populations that are sensitive to RARA agonists and identify patient populations that will benefit from treatment with RARA agonists. The methods may comprise administering RARA agonists to patient populations.
Claims22
A method of treating a disease or condition selected from the group consisting of non-acute promyelocytic leukemia acute myelogenous leukemia (non-APL AML) and myelodysplastic syndrome (MDS) in a subject, the method comprising a step of:
- administering tamibarotene to the subject, wherein a PBMC sample or an enriched PBMC sample from the subject is determined to have an elevated IRF8 mRNA level relative to a threshold level determined by IRF8 mRNA levels observed in comparable samples from a population of subjects having the same disease or condition.
A method of diagnosing, prognosing, or treating a subject suffering from non-APL AML or MDS comprising the steps of:
- a. obtaining a PBMC sample or an enriched PBMC sample from the subject;
- b. determining in the sample an IRF8 mRNA level;
- and
- c. administering a therapeutic composition comprising tamibarotene if
- the IRF8 mRNA level is equal to or above a threshold level, wherein the level is determined by IRF8 mRNA levels observed in comparable samples from a population of subjects having the same disease or condition.
A method comprising:
- a. detecting a RARA mRNA level in a PBMC sample or an enriched PBMC sample obtained from a subject with non-acute promyelocytic leukemia acute myelogenous leukemia (non-APL AML) or myelodysplastic syndrome (MDS), wherein the RARA mRNA is transcribed from a RARA gene that encodes a functional retinoic acid receptor-α gene and specifically excludes gene fusions that comprise all or a portion of the RARA gene;
- b. detecting an IRF8 mRNA level in the PBMC or enriched PBMC sample;
- c. administering tamibarotene to the subject if the PBMC or enriched PBMC sample expresses either an elevated RARA mRNA level equal to or above a RARA mRNA threshold value or an elevated IRF8 mRNA level equal to or above an IRF8 threshold value, wherein:
- the IRF8 threshold level is determined by IRF8 mRNA levels observed in comparable samples from a population of subjects having the same disease or condition;
- and
- the RARA threshold level determined by RARA mRNA levels observed in comparable samples from a population of subjects having the same disease or condition.
Dependencies are inferred from the claim text.