EHA Abstract

A fascinating study was presented by researchers at Lund University, Sweden, at the recent EHA meeting. They were looking for a suitable target to potentially develop an antibody therapy in CML, a method of attack which would of course be independent of tyrosine kinase function and therefore the problems of imatinib resistance that has been seen in some patients with CML. So far the major limitation for such an approach has been the lack of a cell surface receptor distinguishing Ph-positive from Ph-negative CML stem cells. This may be about to change.

Using gene expression profiling Marcus Järås and his colleagues identified Interleukin 1 Receptor Accessory Protein (IL1RAP) as upregulated in CML CD34+ cells and also in cord blood CD34+ cells as a consequence of retroviral BCR-ABL expression.

Using a 'flow-drop-fish' method they found that CML CD34+CD38-, IL1RAP-positive cells were 99% Philadelphia-positive, whereas CML CD34+CD38-, IL1RAP-negative cells were almost exclusively (97%) Ph-negative. They then generated a polyclonal anti-IL1RAP antibody which seemed to be able to target Ph-positive stem cells. If these observations can be verified, IL1RAP might be the first cell surface biomarker which could distinguish Ph-positive from Ph-negative CML stem cells and could open up a new therapeutic avenue perhaps as an adjunct to TKI therapy.