[I wonder if funding into treating leukemias would be increased in
light of the following. Obviously, one of the advantages of
researching CLL and other leukemias is that treatment response is
pretty easy to track...just do a blood test.]

Received Truth Turned On End In Cancer Research
4/6/2004

Source: Swedish Research Council

It has long been the accepted view of cancer researchers that there
is a difference between the mechanism behind the development of
leukemias, on the one hand, and solid tumors like breast cancer,
prostate cancer, gastrointestinal cancer, etc, on the other. A
research team at the Section for Clinical Genetics at Lund University
is now claiming just the opposite: the same mechanism gives rise to
all non-hereditary forms of cancer. These findings are being
published in Nature Genetics.

A well-known mechanism for the development of cancer is that the
chromosomes in a cell break apart and then recombine in an incorrect
way. At the points of fissure, gene fragments are exposed that can
recombine with so-called fusion genes, yielding fusion proteins.
Leukemias-­blood cancer­-normally develop from cells that contain such
fusion proteins. It is not known how this occurs in detail, but in
some way the fusion proteins prompt formerly normal cells to
transform into cancer cells. On the other hand, solid tumors, which
make up the majority of all cancer cases, have been seen as
developing as a result of certain cells losing the inhibiting
mechanism in the form of so-called tumor suppressor genes that keep
tumors from arising.

"This is no doubt correct in regard to hereditary cancer. But
hereditary cancer accounts for only 5-10 percent of all cancer cases.
We now maintain that all of the others have the same developmental
mechanisms. In non-hereditary cancer forms it is the occurrence of
fusion genes and not the lack of tumor suppressor genes that is
essential," says Professor Felix Mitelman.

Mitelman and his associates Bertil Johansson and Fredrik Mertens have
gathered information about aberrant chromosomes in cancer for years.
In 1997 Nature Genetics devoted an entire issue to the large material
the Lund team had compiled, something that has only happened on one
other occasion (when the human genome was presented). This material
is now available as a large and constantly growing database in the so-
called Cancer Genome Anatomy Project at the US National Cancer
Institute, called the Mitelman Database of Chromosome Aberrations in
Cancer.

In leukemia cells it is rather easy to find fusion genes and fusion
proteins. For technical reasons, this is much more difficult in solid
tumors.

"And if you haven't seen them, you assume that they're not there. But
what has been lacking is appropriate methods of examination," claims
Felix Mitelman.

The research team has found that the number of fusion genes in solid
tumors stands in the same proportion to the number of patient cases
examined with leukemias. This shows that the same mechanisms are
involved: the chance of this match being coincidental is less than
0.0001.

The good thing about this discovery is that it should lead to more
effective treatment of the major cancer forms. For one type of
leukemia, at any rate, there is a medicine that specifically targets
the active fusion protein, and it is both effective and mild.

The downside is that there are probably a very great number of
different fusion genes behind the major forms of cancer. Each
transformation of genes is found in just a few patients.

"Small groups of patients are not of interest to pharmaceutical
companies. On the other hand, it may be that several fusion proteins
have common traits that make it possible to use the same drug to
combat them," hopes Felix Mitelman.

The fact that his research team have now turned on end an established
truth does not mean that other ongoing research on the significance
of genetic factors in the emergence of cancer has also been
overturned, he emphasizes. Much of this research is about the long
road from the first cancer cell to a full-blown tumor, and in this
process tumor suppressor genes are probably of great importance. What
the Lund team has done is to provide a revolutionary new picture of
how this very first cancer cell arises.

###