  Current treatment strategy for chronic myeloid leukemia (CML) mainly includes
inhibition of tyrosine kinase activity, which has dramatically improved the
prognosis of the disease but without cure. In addition some patients may become
drug resistant. Thus there is still the need for other therapies to avoid
resistance and if possible to cure the disease. Loss of p53 is known to play an
important role in the disease progression of CML and causes drug resistance.
Here I propose that in CML, inositol requiring enzyme 1 alpha (IRE1 alpha) may
cause abnormal degradation of p53 mRNA resulting in inhibition of apoptosis in
leukemic clonal cells, which has not been elucidated before. Hence, I propose
that inhibition of endoribonuclease activity of IRE1 alpha with small molecule
inhibitors may provide a novel strategy to enhance p53 function in CML leukemic
clones to overcome the limitations of current treatment regimens.
