Therapeutics to inhibit MLL-menin interaction for treating leukemia
Cell permeable peptides derived from MLL that block the interaction of MLL with menin for the treatment of acute myeloid and acute lymphoid leukemia are disclosed. Small molecules interfere with the interaction of MLL with any of its binding partners.
1. A method of inducing cell death in a malignant hematological cell that exhibits a detectable MLL gene arrangement or an MLL fusion protein, the method comprising:
a. providing a peptide that disrupts the interaction of mixed-lineage leukemia (MLL) and menin, wherein the peptide is capable of interfering with MLL protein binding to menin through a binding region of MLL, the MLL protein comprising an amino acid sequence CRWRFPARPG (SEQ ID NO: 14); and
b. inducing cell death in the malignant cell.
2. The method of claim 1 , wherein the peptide is provided in a concentration of about 1 to about 1000 μM.
3. The method of claim 1 , wherein the peptide is provided in a concentration of about 5 to about 100 μM.
4. The method of claim 1 , wherein the peptide is provided in a concentration of about 10 to about 30 μM.
5. The method of claim 1 , wherein the peptide is delivered intraveneously.
6. The method of claim 1 , wherein the peptide is delivered by infusion.