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17p, TP53, and Me (#1)

Posted by Frederick Wasti
Apr 21 2012

Well, so far in this blog I have been mostly able to avoid getting bogged down in such things as DNA, chromosomes, and genes, etc. However, it is now time to try to cover the relevance of some of these issues, and not just for any old abstract reason, but for the very concrete reason that genetics will have a great impact on my life with CLL - how I should most successfully be treated, how long may I survive, etc. - and these are indeed practical matters much closer to me than the realm of the abstract to be sure.

I do apologize for using a lot of terminology in these discussions (which will take more than one blog entry to complete). However, I do feel that it is possible to come to grips with enough of the following descriptions and explanations ~without~ having to understand it all fully. (Heck, I don't understand it fully myself - <g>.) So, I am asking you to please try to follow along with at least some of the main points in my explanations, ~without~ feeling any need to understand every last bit of minutiae. OK? (Thanks.)

First, let's take a quick look at a typical human "karyotype" - the pattern of chromosomes that is found (usually all tangled up, however) in nearly all of our body cells. (In a karyotype diagram, the chromosomes have been artificially manipulated to be neatly spread apart and organized into their homologous pairs, as shown below.)

As everyone is aware, nearly all of our cells contain chromosomes (23 pairs of them), and on these chromosomes are all the genes that control all of our heredity. The actual control of everything is handled through the genes determining how every protein (every enzyme and every structural protein in our bodies) is produced. Ordinarily this control is invisible to us as we live, but mistakes - "mutations" - do occur occasionally. Most mutations can be corrected and/or removed by remarkable cell machinery, especially early in life. However, the rate of mutations does tend to increase with age, and our abilities to neutralize their effects does simultaneously tend to decrease with age. Such is aging...

Most cells in our bodies are supposed to have finite life spans - that is to say that most cells are supposed to be born, to live a functional life, and then to die, to make room for newer, more productive cells to take their place. But, as we know with forms of cancer this does not properly happen. Cancer cells lose the ability to easily die, and we all know how serious that problem can become.

Chromosomes, which exist in pairs, can be thought of as being strings of genes. The genes also exist in pairs, with each gene being located on each matching member of a pair of chromosomes. Our 23 pairs of chromosomes are numbered by size, and the pair in question here is the 17th pair. (If you're on the ball here, you have probably just figured out where the "17" in this entry's subject line comes from - <g>.)

Under the right conditions, each chromosome has approximately the shape of an "X", with the connecting point of the "X" sometimes close to the middle for some of the chromosomes and sometimes close to the end in some of the other chromosomes (making a few of them almost seeming to be "Y" in shape). In the terminology of genetics, the short ends of the X shape are referred to as the "p" ends and the longer ends are the "q" ends. (And now you may be recognizing why the first three characters in the subject line are "17p" - <g>. As it turns out, a high percentage of my leukemic lymphocytes have a deletion on one or both of the short ends of my 17th chromosomes.) (This deletion is not found in 99.999% of the cells in my body, but is found only in my mutated leukemia cells.)

If we take a closer look (just for simplicity) at just one half of a 17th chromosome (the "p" short end to the left and the longer "q" end to the right, it would look like the following - the codes along the side are how scientists map locations on each chromosome). I have added a red arrow where the unfortunate 17p deletion occurs in a few of us CLL patients (the exact location is known as 17p13.1):

It turns out that having a 17p deletion (sometimes referred to as "17p-", where the minus indicates the missing deletion) is significant in some types of cancers, some more so than in others. In the case of my particular leukemia, chronic lymphocytic leukemia (CLL), it does make a large difference. A CLL patient who does not have this deletion has a much higher probability of the disease progressing quite slowly, as the name "chronic" would suggest. However, in contrast, those 5% or 10% or so of us that have CLL and also have a deleted 17p chromosome turn out to have a form of CLL that progresses much more rapidly (almost as if it were an acute form of leukemia) and also does not respond well to conventional chemotherapies used for most CLL patients.

I will try to get a little closer to the bad news about having the 17p deletion in my next entry. (In the meantime, please do try to bear with me here - it is ~not~ necessary to understand all of this to succeed at following my story, so please just try to be patient and you ~will~ absorb enough for this to be useful - trust me, please.)

Categories: Leukemia