Heads Up! This is important news

[Guest guest]

Hello Folks,

This is NEW information on how CML cells DO NOT crowd out healthy cells, as

was long thought to be the case, but actually kill them. While this sounds

like it is bad news, it is good news as it sheds new light into this area

and paves the way for science to work on the compound that can be used

adjunctively with IM to reverse this action.

Best,

Cheryl-Anne

CML found to wield 'death factor' that kills normal blood marrow cells

ANAHEIM - Based on surprising results from animal experiments, researchers

at The University of Texas M. D. Cancer Center have revamped common

beliefs about how chronic myeloid leukemia (CML) functions within bone

marrow - a discovery they hope may some day lead to additional therapeutic

strategies.

In a study presented at the annual meeting of the American Association for

Cancer Research (AACR), they found that CML does not " crowd out " normal

blood cells in the bone marrow, as has long been thought, but actually kills

those healthy cells through use of a unique cell " death factor. "

Those destructive proteins, known as lipocalin 24p3, work to promote the

development of leukemia by giving the cancer room to grow and spread, making

it easier to invade the bone marrow and spleen, say the researchers.

Because they also show in this study that blocking the protein with an

antibody in mouse cell experiments will restrain the ability of the cell

death protein to kill normal bone marrow cells, the researchers suggest that

a therapy that could disable 24p3 might prove useful to CML patients when

combined with traditional treatment, such as with Gleevec.

" We don't yet have a therapy that can be tested in humans, but our hope is

that this work can lead to development of such a one-two punch, " says the

study's principal investigator, Ralph Arlinghaus, Ph.D., a professor and

chair of the Department of Molecular Pathology.

In the least, the research demonstrates that CML is much craftier than had

been suspected, he says. Before this study, no one knew that the 24p3 mouse

protein (known in humans as neutrophil gelatinase-associated lipocalin, or

NGAL) had any involvement in leukemia, Arlinghaus says.

The protein is a normal component of cells and is believed to have a variety

of functions. But the " BCR-ABL oncoprotein (encoded by the Philadelphia

chromosome, a translocation of genetic material responsible for most CML)

appears to hijack 24p3 and change it structurally to become a cell killer, "

he says.

The secreted proteins appear to destroy bone marrow stem cells responsible

for producing red blood cells as well as platelets, but leukemia cells are

believed to be resistant to the effects of 24p3, the researchers found.

" This provides an understanding of how Philadelphia chromosome-positive

cells can overcome and grow effectively in a crowded marrow environment, "

Arlinghaus says.

" The disease may begin with a single translocation, but with the death

factor helping to continuously clear the way, the leukemia cells can take

over the entire marrow, " he says. " And when you block the protein, leukemia

cells have a hard time growing in the marrow. The goal now is to study this

active process further in human leukemia cells.

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The study, funded by a grant from the National Cancer Institute, will be

presented by its first author at AACR by Hui Lin, research investigator in

the Department of Molecular Pathology.