Sensitizing CML Precursors to GVL

Bethesda, Maryland -

Chronic myeloid leukemia (CML) is a cancer of the myeloid committed stem cell, which is caused primarily by the oncogenic chimeric protein BCR-ABL.  Immune responses are known to control progression of CML.  For example, patients with CML taking interferon that have higher NK cell activity live longer.  There are many proteins that the immune system may recognize on CML cells, for example peptides from the BCR-ABL fusion protein, peptides from PRAME, or peptides from Aurora kinase.

In a recent paper (Yong et al. Primitive quiescent CD34+ cells in chronic myeloid leukemia are targeted by in vitro expanded natural killer cells, which are functionally enhanced by bortezomib. Blood 2008 Oct 15) the efficacy of NK mediated killing on cycling versus quiescent CML cells that were CD34 positive was studied.

The investigators found that:

a) quiescent CML CD34 cells were more resistant to NK cell killing than cycling cells

b) treatment of the quiescent CML CD34 cells with velcade increased expression of TRAIL receptors

c) treatment with velcade increased sensitivity to NK cell killing.

Since Velcade is already in clinical use, the possibility of using it to sensitize CML cells to immune killing could be a neat clinical trial possibility.