Therapy for MLL-rearranged leukemia
Provided are methods for treating MLL-rearranged ALL by administering to a patient an HDAC inhibitor alone or in combination with a DNA demethylating agent. Also provided are methods of treating MLL-rearranged infant ALL. Methods of treating cells by these agents are also provided. Additionally, disclosed is a method for screening for compounds capable to treat MLL-rearranged ALL, in particular, MLL-rearranged infant ALL. In one embodiment, the HDAC inhibitor is romidepsin.
1. A method of treating a mixed-lineage leukemia (MLL)-rearranged infant acute lymphoid leukemia (ALL) comprising administering to a patient romidepsin in combination with a DNA demethylating agent selected from the group consisting of 5-azacytidine (azacytidine), 5-azadeoxycytidine (decitabine), zebularine and procaine.
2. The method of claim 1 , wherein the dose of romidepsin ranges from about 0.5 mg/m 2 to about 28 mg/m 2 for intravenous administration.
3. The method of claim 2 , wherein the dose of romidepsin ranges from about 8 mg/m 2 to about 14 mg/m 2 .
4. The method of claim 3 , comprising infusing the dose of romidepsin to the patient over a 4 hour period.
5. The method of claim 4 , comprising infusing the dose of romidepsin to the patient on days 1, 8 and 15 of a cycle.
6. The method of claim 5 , comprising repeating the cycle every 28 days.
7. The method of claim 1 , wherein the dose of romidepsin ranges from about 1 mg/m 2 to about 300 mg/m 2 for oral administration.
8. The method of claim 7 , wherein the dose of romidepsin ranges from about 25 mg/m 2 to about 75 mg/m 2 .
9. The method of claim 1 , wherein the DNA demethylating agent is 5-azacytidine.
10. A method for treating an MLL-rearranged infant ALL comprising administering to an MLL-rearranged infant ALL patient romidepsin in combination with a DNA demethylating agent, comprising intravenously infusing over a 4 hour period the romidepsin in a dose of 14 mg/m 2 to the patient on days 1, 8 and 15 of a cycle, wherein the cycle is repeated every 28 days.
11. The method of claim 10 , wherein the DNA demethylating agent is 5-azacytidine.