Druker updates stem cell research

By Jerry Call
LRG scientific coordinator

Last month’s issue of the Life Raft Group newsletter reported that researchers are working to understand and target stem cells in leukemia. After the newsletter was published, we found a relevant interview with Dr. Brian Druker in Medscape by Sally Church, Ph.D. (See the Medscape Web site, www.medscape.com/ viewarticle/496015).

Druker is credited with bringing Gleevec into clinical practice for chronic myelogenous leukemia (CML). The following excerpt is presented because it may have important implications for GIST patients.

Church interviewed Druker in conjunction with the American Society of Hematology’s 46th annual conference held in December. The interview is titled: “Imatinib and Beyond — New Developments in the Treatment of CML: An Interview with Brian Druker, M.D.”

Medscape’s Church: In terms of this conference, what presentations have excited you?

Dr. Druker: “Within CML, the most exciting have been the AMN107 and BMS-354825 compounds, because the response rates in imatinib-resistant patients have been so high. The other presentation, which I think was, in some respects, overlooked, was Tessa Holyoake's poster. She was addressing what I view as the most pressing problem in CML patients, and that it is not the issue of relapse, but what I would call molecular persistence. So, if you look at imatinib, 98 percent of patients have normal blood counts, 84 percent of patients have a complete cytogenetic response, but only 5 percent of patients are molecularly negative or have undetectable levels of the bcr-abl transcript. Thus, I would consider the majority of patients having molecular persistence, meaning good responses, but still they have molecularly detectable disease. The issue is, why can't you eradicate the disease?

“What Dr. Holyoake has been doing is purifying progenitor cells from CML patients and looking to see, much like we did in relapse patients, whether the bcr-abl kinase is “on” or “off.” It looks, from her early studies, that the bcr-abl kinase is “on.”

“She also has some data that suggest that some of the CML progenitor stem cells may be resistant to imatinib. The issue is: with a more potent inhibitor, will you be able to achieve a higher rate of molecular negativity? Certainly, from the dose escalation studies, there is a suggestion that we may be able to, and to me ultimately the excitement of the new kinase inhibitors that are coming along is that we may be able to achieve a higher rate of molecular negativity, but it may be more complicated than just a more potent inhibitor.

“Some of her data suggest that quiescence of stem cells may also contribute to molecular persistence, so it may well be that, with a more potent inhibitor, we will get a higher rate of molecular negativity, but we may not yet eradicate the clone. And we may yet need other targets or other mechanisms to attack the leukemic cell to eradicate the disease and cure patients.

“These are very exciting times; we may see higher remission rates, high rates of molecular negativity, but we still may have to learn how to eradicate those last few cells. Ultimately, the work looking at why we can't eradicate the last, few cells will be critical to designing the best strategies to eradicate the disease.”