Methods of predicting resistance to JAK inhibitor therapy

• US 10,155,987 B2
• Filed: 06/12/2013
• Issued: 12/18/2018
• Est. Priority Date: 06/12/2012
• Status: Active Grant

• Current Assignee: Dana-Farber Cancer Institute
• Original Assignee: Dana-Farber Cancer Institute
• Inventors: Sattler, Martin, Deshpande, Anagha, Griffin, James D.
• Primary Examiner(s): GOLDBERG, JEANINE ANNE
• Application Number:
  US13/916,169
• Publication Number:
  US 20140004516A1
• Time in Patent Office: 2,015 Days
• Field of Search: None
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: G01N 33/574 for cancer

Abstract

This present invention provides methods of treating of assessing/monitoring the responsiveness of a cancer cell to JAK inhibitor therapy.

Claims

1. A method of treating a subject having a myeloproliferative malignancy comprising:

a) detecting the absence of one or more point mutations selected from the group consisting of R938L, I960V, and E985K in the kinase domain of the JAK2V617F polypeptide in a biological sample obtained from the subject;

b) diagnosing the subject as responsive to a JAK inhibitor selected from the group consisting of ruxolitinib, CYT-387, TG101348, AZD1480, and lestaurtinib; and

c) administering the JAK inhibitor to the subject diagnosed to be responsive to the JAK inhibitor.

2. The method of claim 1, wherein the myeloproliferative malignancy is polycythemia vera, essential thrombocythemia, idiopathic myelofibrosis, acute myeloid leukemia, or myelodysplastic syndrome.

3. The method of claim 1, further comprising detecting the absence of point mutation Y931C or G935R.

4. The method of claim 1, wherein the subject is a mammal.

5. The method of claim 1, wherein the subject is a human.

6. The method of claim 1, wherein the biological sample is a tissue biopsy, whole blood, serum, plasma, saliva, or urine.

7. The method of claim 6, wherein the biological sample is whole blood, serum, or plasma.

8. The method of claim 1, wherein the method alleviates the symptoms of the myeloproliferative malignancy.

9. The method of claim 1, wherein the subject is asymptomatic for cancer recurrence.

10. The method of claim 1, wherein step (a) comprises using a mutant polypeptide-specific antibody that specifically binds to JAK2V617F with a mutation at amino acid position 938, 960, or 985.

11. The method of claim 1, wherein step (a) comprises using polymerase chain reaction.