METHODS FOR THE DETECTION AND TREATMENT OF LEUKEMIAS THAT ARE RESPONSIVE TO DOT1L INHIBITION

摘要

Disclosed are: (i) methods for identifying leukemia patients who (or leukemia cells that) do not exhibit an MLL-translocation, rearrangement or MLL-partial tandem duplication but who are nonetheless susceptible to treatment with DOT1L inhibitors; and (ii) methods for treating leukemia patients who (or inhibiting proliferation or inducing apoptosis of leukemia cells that) do not exhibit an MLL-translocation, rearrangement or MLL-partial tandem duplication with DOT1L inhibitors. The patients identified as susceptible and the patients (or cells) treated exhibit elevated expression of a HOX cluster gene or of a HOX cluster-associated gene. Elevated expression of such genes can be measured, e.g., by quantitating the relevant RNA and comparing it to that of a healthy individual (or cell) or to a predetermined standard or it can be inferred by determining whether the patient or cell possesses a mutation that is associated with elevated HOX cluster gene or HOX cluster associated gene expression and thereby inferring that the relevant expression with be elevated.

主权项

1. A method for determining whether a leukemia patient is susceptible to treatment with a DOT1L inhibitor, said method comprising:
comparing a quantified level of a HOX cluster RNA and/or a HOX cluster-associated RNA in a tissue sample from said leukemia patient with a quantified level of a HOX cluster RNA and/or a HOX cluster-associated RNA in a tissue sample of a healthy human subject or with a predetermined threshold said quantifications having been accomplished by amplifying RNA in said tissue sample with a primer pair that is specific for HOX cluster gene RNA or a HOX cluster-associated gene RNA,wherein said tissue sample from said leukemia patient does not comprise an MLL-translocation, MLL-rearrangement of MLL-partial tandem duplication; andwherein, if an elevated level of said HOX cluster RNA and/or a HOX cluster-associated RNA in said leukemia patient tissue sample as compared to said HOX cluster RNA and/or a HOX cluster-associated RNA in said healthy human subject tissue sample or threshold is present, the elevated level indicates the susceptibility of said patient to treatment with a DOT1L inhibitor.