Treating chronic myelogenous leukemia (CML)
Methods for treating chronic myeloid leukemia (CML), e.g., BCR-ABL inhibitor imatinib mesylate (IM)-resistant CML, using combination treatments, e.g., combined treatment with a BCR-ABL inhibitor, e.g., IM, and a MEK inhibitor, e.g., trametinib.
1. A method for treating BCR-ABL independent imatinib mesylate (IM)-resistant chronic myeloid leukemia (CML) in a mammalian subject, the method comprising:
detecting a level of PRKCH mRNA in a sample comprising leukemic cells from the subject;
comparing the level of PRKCH mRNA in the sample to a reference level; and
administering a combination of a BCR-ABL inhibitor and a MEK inhibitor to a subject who has a level of PRKCH mRNA above the reference level.
2. The method of claim 1 , wherein the BCR-ABL inhibitor is imatinib, Nilotinib; Dasatinib; Bosutinib; Ponatinib; Bafetinib; or thiazol or a thiazol derivative.
3. The method of claim 2 , wherein the BCR-ABL inhibitor is imatinib.
4. The method of claim 1 , wherein the MEK inhibitor is Trametinib, Selumetinib, MEK162, PD-325901, cobimetinib, CL-1040, or PD035901.
5. The method of claim 4 , wherein the MEK inhibitor is trametinib.
6. The method of claim 1 , wherein the subject is human.
7. The method of claim 1 , wherein the level of PRKCH mRNA is determined using RNA in situ hybridization, Southern or Northern analyses, polymerase chain reaction analyses and probe arrays.
8. A method for treating BCR-ABL independent imatinib mesylate (IM)-resistant chronic myeloid leukemia (CIVIL) in a mammalian subject, the method comprising:
detecting a level of PKCeta protein in a sample comprising leukemic cells from the subject;
comparing the level of PKCeta protein in the sample to a reference level; and
administering a combination of a BCR-ABL inhibitor and a MEK inhibitor to a subject who has a level of PKCeta protein above the reference level.
9. The method of claim 8 , wherein the BCR-ABL inhibitor is imatinib, Nilotinib; Dasatinib; Bosutinib; Ponatinib; Bafetinib; or thiazol or a thiazol derivative.
10. The method of claim 9 , wherein the BCR-ABL inhibitor is imatinib.
11. The method of claim 8 , wherein the MEK inhibitor is Trametinib, Selumetinib, MEK162, PD-325901, cobimetinib, CL-1040, or PD035901.
12. The method of claim 11 , wherein the MEK inhibitor is trametinib.
13. The method of claim 8 , wherein the subject is human.
14. The method of claim 8 , wherein the level of PKCeta protein is determined using an immunoassay.