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17p, TP53, and Me (#2)

Posted by Frederick Wasti
Apr 22 2012

[Please note that, if you haven't slogged your way through my earlier post entitled "17p, TP53, and Me (#1)", below, you really should tackle that before starting with this continuation - Thanks.]

In my last post, "17p, TP53, and Me (#1)", I tried to introduce the concept that chromosome 17 can suffer from a deletion. I pointed out that such a deletion is deleterious for any CLL patient, as it tends to cause a more rapid disease progression as well as tending to increase the difficulty of therapy using standard treatments. What I would like to try to do in this entry is to explain a bit about why this is so.

As I have mentioned previously, most body cells are supposed to have a finite life span, and they ordinarily are supposed to die (or be killed) when their normal life span is up. This natural programmed process of cell death is known by the term "apoptosis" ("ay-pop-TOE-sis"). Apoptosis is generally caused by either some sort of a cellular stimulus or by the lack of some sort of a cellular suppressor.

(Yes, I know this is starting to sound a bit technical, but please hang in there just a bit more - please remember that you do ~not~ need to understand every detail to "get the big picture".)

Now let me try to get to the significance of the "TP53" (sometimes just called "p53") in the subject line. In this case the "P" or "p" is not being used to refer to the short "p" end of a chromosome (as it was in "17p"), but is instead standing for the word "protein". Remember that genes control the production of proteins, and so genes are sometimes named for the proteins they control. In this particular case, "TP" stands for "tumor protein", and TP53 has been found to be a very important protein that regulates apoptosis - to encourage cells to reproduce when cell growth is desirable, but to also act as a "brake" on cell growth when excess growth would only lead to cancer. In other words, the TP53 gene is a special tumor-regulating or cancer-regulating gene, ordinarily capable of bringing on apoptosis in a cell whose time is right to die.

As it turns out, improper functioning of the TP53 gene is a significant factor in approximately one-half of human cancers. When the TP53 gene fails to apply the brakes in a cell with defective DNA (i.e., a cell with a mutation that cannot be corrected), the mutated cell can start growing in number uncontrollably, and that is, of course, what cancer ultimately represents - uncontrollable reproduction of defective cells that have lost the ability to die naturally.

Now, to connect the TP53 gene back to my earlier description of chromosome 17p deletion, the fact is that, when a 17p deletion occurs, the TP53 gene is lost, since it is located near the end of the 17p chromosome. (It is also possible for the TP53 gene to be mutated without a 17p deletion, but the effect is still the same.) In CLL, the absence of functioning TP53 genes in lymphocytes (generally due to 17p deletions) leaves the lymphocytes with no way to die - they have no mechanism to undergo apoptosis.

Now the good news for over 90% of CLL patients is that, since their lymphocytes do have functioning TP53 genes, their cells do have, at least to some extent, the ability to undergo programmed death. Furthermore, standard drugs that can encourage the TP53 gene to suppress cell division can be effective in slowing cancer growth down.

But, the bad news for those of us CLL patients who have 17p chromosome deletions is that cancerous cell growth is naturally much more rapid (because there is no TP53 suppressor "brake" to counteract excessive growth), and standard therapies that work to trigger the TP53 gene into bringing about apoptosis (which do help in most CLL patients) become rather ineffective when used in those of us who lack functional TP53 genes.

Categories: Leukemia