This invention provides a much needed improvement in the treatment of leukemias, in particular acute lymphoblastic leukemia (ALL) and chronic myelogenous leukemia (CML) by overcoming drawbacks associated with current treatments of leukemias, such as drug resistance.

While many synergistic chemotherapeutic combinations are known for treating various cancers, there remains a need for additional combination therapies for cancers, including leukemias.

The human oncogene/oncoprotein B-cell CLL/lymphoma 6 (zinc finger protein 51), also known as BCL6,is known as having a role in B-cell differentiation and proliferation, and is recognized as an oncogene/oncoprotein. However, its role in resistance to chemotherapeutic agents and particularly its role in causing cancer cells to be refractory to chemotherapeutic agents have not been established. The inventors have generated data showing that treatment with certain chemotherapeutic agents results in an increase in expression of BCL6, which decreases or abolishes the potency of the chemotherapeutic agents against the cancer cells. Treatment of the cells with an inhibitor of BCL6 thus restores the cell-killing activity of the chemotherapeutic agent, and improves treatment outcome. The methods of treatment according to the invention involve a synergistic action between BCL6 inhibitors and chemotherapeutic agents, such as those targeting the tyrosine kinase activity of BCR-ABL.

Inhibition of BCL6 represents a novel approach to preventing drug-resistance in BCR-ABL1-driven ALL and CML.

Inhibition of BCL6 may occur by using small molecule inhibitors, such as described in PCT/US2007/024571 and/or peptides that block co-repressor binding to BCL6, such as described in PCT/US2004/042418.

File Number: 2009-005 

Web site: http://www.chla.org/site/c.ipINKTOAJsG/b.357948...

Disease: Cancer

Other Information:

Development Stage:

Our inventors have generated both in vitro and in vivo data with Imatinib and Nilotonib. The in vivo data shows decreased leukemia infiltration and increased survival in mice treated with the combination of a BCL6 inhibitor and tyrosine kinase inhibitor (available under CDA).