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Editor's Note: Peter Rowbotham attended the 2001 meeting of the American Society of Hematology, held from Dec. 7-11 in Orlando, Florida, U.S.A. Rowbotham, whose wife has CML, has long dedicated himself to researching new treatment advances and passing that information along to others. Here, his series is presented verbatim.
By Peter Rowbotham
[Note from Peter: This report, and any following reports, are based on written notes which may be inaccurate or incomplete. Patients should check with medical professionals as necessary.]
On the final day of ASH, Dr. Druker was awarded the William Dameshek prize. This award is for an outstanding contribution to the field of hematology. Druker's role in the development of STI571 has earned him many awards. As the President of ASH said, he is an "extremely worthy recipient of this prize."
Following the award ceremony at the Presidential Symposium, there were papers given by three invited speakers. This all takes place in an enormous hall, which is the size of a very large aircraft hangar. Three huge screens behind the podium show the speakers and their slides to an audience which I thought (unscientifically) might be in the thousands. It is an honour for these speakers to give papers at the Presidential Symposium, and they seem to be chosen on the basis of the importance of their work and their speaking ability.
The first speaker was Jean Wang of the University of California San Diego, and her topic was "Bcr-Abl in the Regulation of Apoptosis." She more than lived up to her billing and gave a great performance on an important topic. In my judgment, she is someone worth watching in the future. Many will be aware of her thought-provoking paper in Nat Med. 2001 Feb on the topic "Induction of Apoptosis in Chronic Myelogeneous Leukemia Cells through Nuclear Entrapment of BCR-ABL Tyrosine Kinase." Bcr-Abl causes proliferation of the WBC, and the issue of apoptosis (natural cell death — sometimes referred to as cell suicide) is highly important.
Cancer cells evade apoptosis, and Bcr-Abl cells are no exception; in fact Bcr-Abl itself specifically inhibits apoptosis! However, as Wang showed, there is a way of turning Bcr-Abl around, changing its mind as it were, so that it becomes an inducer of apoptosis. In most cells (not red blood cells or platelets) there is a nucleus and Bcr-Abl runs in and out of the nucleus. If it can be trapped in the nucleus, and not allowed out into the rest of the cell, it will induce (cause) apoptosis. In other words, trap Bcr-Abl (the bad guy) in the cells nucleus, and the cell will self-destruct. Sounds good, doesn't it?
STI571 allows Bcr-Abl to enter the nucleus, but then it normally gets pumped out. This can be stopped with the drug Leptomycin B (LMB), which I have written about a number of times previously. The whole procedure is more complex than I can indicate here, but the upshot is that the combination of LMB and STI produces dramatic results. Wang found no surviving Bcr-Abl cells in culture (i.e. in the lab experiments) after two weeks. So this combination kills the Bcr-Abl cells without any problem, and so, theoretically, by locating and trapping some of the Bcr-Abl in the nucleus you could actually use the Bcr-Abl itself to cure CML!! Unfortunately, LMB is too toxic to be used on patients, but I cannot see why a similar non-toxic drug could not be found which would do the same job. This is incredibly exciting work. Presumably the technique could be used to purge autologous cells, making cures from autologous transplants a practical possibility. Let us all hope that Wang's research lab (working with drug companies) will come up with something that can be used for patient treatment.
We know that STI571 inhibits the c-Kit tyrosine kinase and this has proved very valuable for GIST patients. We also know that it inhibits PDGF (platelet derived growth factor), and this promises to be useful in the treatment of some CMML patients. Jane Apperley, who is a highly thought of researcher at Hammersmith in London, gave a talk (abstract #3031) on the previous day about a 19 year old patient who had been taking STI for this PDGF inhibition (but not for CMML). She showed a photo of the patient's back and chest prior to therapy. It was just a mass of red, and he had very little skin left at all. He was in excruciating pain, and a gasp went up from the audience when the photos were displayed. She also showed a photo of his face, which was covered in large disfiguring bumps. It was not a pleasant experience to see this. Then she showed the healing that had taken place after a short period on the drug, and then the patient's face. Another audible gasp went up from the audience. He was a changed man, with an almost normal facial expression. I relate this merely to indicate the extraordinary power of this drug, and the huge advances that are being made in the treatment of malignancies of many different kinds. We are entitled to look forward to many more such advances in the next few years.
So let's hang in there!
Peter
(There were many papers on PCR testing. This is the test of the future, and patients should push for it to become more universally available. It is a very important way to monitor CML.)
Source: Peter Rowbotham, reprinted with permission
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