Methods of predicting resistance to JAK inhibitor therapy

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.