This post was way too long so I decided to cut it in half. I will post the second part tomorrow. Only then will today’s title make complete sense.
Anyway, I have it, I have it! Yes, the FULL recently published Johns Hopkins myeloma stem cell study that I mentioned a couple of days ago. Okay, I confess that I have had it in my possession since last Sunday, when a very kind blog reader (thank you thank you thank you!) sent it to me, but just haven’t gotten around to writing a post about it. The study, by the way, was conducted by a team led by Dr. William Matsui and published in the January 1 2008 issue of “Cancer Research.” You can view the abstract here: http://tinyurl.com/2yuru9.
Before I go on, though, I wanted to mention that another blog reader posted an interesting New York Times article on the controversy surrounding the cancer stem cell theory and other interesting info, so if the issue of stem cells is your cup of tea, please go read Carla’s comment on my “Stem cells and myeloma” post, Jan 12th.
Back to us. I have to admit, reading this stem cell study was not exactly as fun and easy as reading one of the Harry Potter books, but I found it almost as engrossing. The study begins by providing a bit of background, including this: “Early studies examining a murine model of multiple myeloma suggested only a minority of cells were capable of clonogenic growth.” Hmmm, so only a tiny percentage of myeloma cells can clone themselves…I didn’t know that. I thought they were all capable of creating clones. Live and learn.
Myeloma stem cells are mentioned in a 1977 study (full text: http://tinyurl.com/2d8z3n), which, by the way, shows black and white photos of myeloma cells for those who might be interested. Anyway, according to the Johns Hopkins investigators, this early study showed that “the cloning efficiency of primary multiple myeloma specimens was 1 in 1,000 to 100,000 cells. To date, it has remained unclear whether these clonogenic cells are distinct from the plasma cells that constitute the majority of tumor cells.”
Then, in 2004, Dr. Matsui et al published a study (full text: http://tinyurl.com/2233wp) in “Blood” on clonogenic myeloma cells. Clonogenic, by the way, has two meanings: 1. “giving rise to a clone of cells” and 2. “arising from or consisting of a clone.” I went through the 2004 study, which reported that “highly clonogenic cells from both human MM cell lines and primary patient samples do not express CD138, but rather markers that are characteristic of B cells.” This rather baffling sentence will, I hope, become clearer after the upcoming section on CD138 (and part II, which I will post tomorrow, should also help in that sense). The 2004 study also suggested that, like chronic myeloid leukaemia or CML, “MM is another example in which cancer stem cells are a rare cell population that is distinct from the differentiated cells that comprise the bulk of the disease.”
CD138. Now I am going to delve into some rather difficult material that has to do with this thing called CD138. Also known as syndecan-1, CD138 “is “a heparan sulfate proteoglycan expressed on the surface of, and actively shed by, myeloma cells.” I know, I know…Let’s see if this will clarify matters: proteoglycans are “glycoproteins but consist of much more carbohydrate than protein; that is, they are huge clusters of carbohydrate chains often attached to a protein backbone,” according to Prof. Kimball’s Biology Pages. (Hmmm, lots of carbs plus some protein…pasta with meat sauce! )
Seriously though, it doesn’t really matter if we don’t completely grasp what CD138 is. What’s important is that we understand the following excerpt from the 2004 Johns Hopkins study. CD138 “is the most specific marker for normal and MM plasma cells. However, normal CD138+ plasma cells appear to be terminally differentiated and unable to proliferate, and there have been few studies using this marker to study the proliferative capacity of MM cells.”
Not the easiest stuff to digest, eh! Well, let’s see if I can explain what CD138 is in a few simple words (if I make any mistakes, please let me know): in sum, CD138 is a thingie (ok, a proteoglycan) sticking to the surface of regular myeloma cells—the ones, that is, that are NOT able to clone themselves. These are the CD138 "plus" myeloma cells. Patients whose myeloma cells release, or "shed," CD138 (CD138 "negative" cells) into the serum have a worse prognosis than those whose myeloma cells still have it. Hence it is a helpful prognostic marker (for more info, see this 2002 “Blood” study: http://tinyurl.com/2h26uq). CD138 levels can be measured in MGUS patients, too (see this 2006 "Neoplasma" abstract: http://tinyurl.com/yr9vzd).
A September 2007 “Blood” study (see abstract: http://tinyurl.com/2slg3t) confirms that “High levels of shed syndecan-1 in myeloma patient sera correlate with poor prognosis and studies in animal models indicate that shed syndecan-1 is a potent stimulator of myeloma tumor growth and metastasis.” So again we see that if CD138 is shed into the myeloma “microenvironment,” this is bad news for us (poor prognosis etc.). Interesting aside: this is true for CLL patients as well (see this January 2008 abstract: http://tinyurl.com/3ap8ba). Connections, connections.
Ok, that’s it for today! Phew.