Day before yesterday, in part one, we saw that the only myeloma cells capable of cloning themselves are the ones that do not express CD138. The following excerpt from the Johns Hopkins study says it well: “multiple myeloma cell lines and primary bone marrow contain small populations of clonotypic B cells that do not express the characteristic plasma cell surface antigen CD138 and are capable of clonogenic growth and differentiation into multiple myeloma plasma cells in vitro and in vivo.”
Myeloma stem cells, therefore, don’t have CD138 sticking to their surfaces. Herein lies a big difference between regular myeloma cells and myeloma STEM cells: the former have CD138, the latter don’t. Enough said on CD138. Let’s look at other findings now.
I mentioned in my January 12th post that the capable-of-cloning-themselves myeloma cells are resistant to chemotherapy AND look like normal memory B cells AND also display "cellular properties characteristic of normal stem cells, suggesting cancer and normal stem cells share multiple mechanisms that promote drug resistance.” In fact, according to the 2008 stem cell study, both myeloma and normal stem cells have “intracellular detoxifying enzymes,” enzymes that, as I understand it, shoo away the chemo toxins, thus protecting the stem cell from apoptosis. This would provide a good explanation for why myeloma eventually becomes resistant to chemotherapy agents.
So, in sum, what does all this mean? In the researchers’ words, “Because cancer stem cells are a relatively low frequency population in most tumor types, the true inhibition of these cells is likely to be difficult to assess early after treatment, and a prolongation of disease remission would be required to establish such activity.” Well, that doesn’t sound very encouraging, does it?
Back in the middle of November, in a private exchange, a blog reader compared myeloma to a tank of water with a tap and a drain, an analogy he took from the film "Lorenzo’s oil," (those interested can go read a 2007 update on the real ALD story: http://tinyurl.com/2yjyjx). Anyway, the blasted paraprotein shoots out of the "tap," and the drain hole (our kidneys) gets rid of it. Myeloma cells, he was told by his haematologist, have a half-life of 5-6 weeks (I have been trying to find an online reference to this, but so far, on the UK freelite website, I found only that the “the serum half-life of intact immunoglobulin IgG is 20-25” days, so I will ask my haematologist about this in February). In other words, the cells stay in the body for that time and are then expelled via the kidneys.
Point is, are stem cells our "tap"? If so, how can we turn it off? I sure would like an answer to those questions! I would like to add that during yesterday’s meeting, Dr. Benelli suggested another "tap" theory to me, which I will be looking into in the next few days. Interesting times.
Concluding remarks. In the short term, yes, this stem cell research is exciting news but that’s what it remains: news. It has little relevance to us patients. For now. It holds promise for the future, though, indeed let’s hope the very near future. A finding that may prove to be useful is that “the developmental signaling pathway Hedgehog is up-regulated in multiple myeloma stem cells and regulates cell fate decisions.” So we meet again, Mr. Hedgehog! Back in early August, on August 2 and 3 to be precise, I wrote about cyclopamine, a poison contained in corn lilies that was found to be a Hedgehog pathway inhibitor (see my page on cyclopamine).
A couple of days ago, in a private exchange, an MMA list member asked me if the stem cell study had changed my supplement plans for the future. I answered yes, it has, in the sense that I hadn’t really thought seriously about taking parthenolide until I read about myeloma stem cells and how parthenolide and DMAPT (water-soluble form of PTL) annihilate leukaemic stem cells in vitro. So parthenolide shot right to the top of my supplements-to-try list. I am now planning to test parthenolide in March, after the Biocurcumax experiment has ended.
Summary of the main points made in the stem cell study, from my point of view:
- clonogenic myeloma stem cells do not express the characteristic CD138 antigen.
- myeloma stem cells constitute less than 2% of the myeloma "population."
- myeloma stem cells look like memory B cells.
- myeloma stem cells display normal stem cell characteristics that protect them "from toxic injury."
- like normal stem cells, nearly all myeloma stem cells (>98%) studied were in the quiescent (dormant, inactive) state, which is possibly another "major mechanism of drug resistance."
- conventional chemotherapy doesn’t affect myeloma stem cells.
Thank you for this interesting and very well written post! I would have never (never) dared to read such difficolt stuff… I’ll tell you about the face of my doctor when I’ll ask him about myeloma stem cells 🙂
I found another article on CD138 known as Syndecan-1 which is in fact required by myeloma cells for growth and progression via alteration of the microenvironment through stimulation of tumor angiogenesis.
Here is another one indicating that high levels of Syndecan-1 correlate with poor prognosis. Also, it indicates possible strategies for myeloma therapy through disruption of Syndecan-1 or its heparin sulphate chains. Gerry