Q. I’m in doubt regarding myelodysplasia – is it multipotent or pluripotent?

A. That’s a great question because it lets us talk about hematopathology (yay!) and also stem cells (which can be confusing unless someone explains some simple stuff).

What is a stem cell?
First, let’s talk about stem cells. The thing that makes a stem cell a stem cell, at least in my mind, is the ability to self-renew. This means that the stem cell can either divide into two daughter cells which will mature into grown up cells, or (and more commonly) it can give rise to two cells: one that will become a mature cell, and another which retains the capacity to divide again. It’s called asymmetric division: instead of giving rise to two of the same cells, you get one regular cell and another stem cell (which can continue this cycle of replication for a long long time).

(Virtually) limitless replication
Most cells have a limited number of times that they can divide. This is because the telomeres (little protective DNA sequences) on the end of the chromosomes get a little shorter every time the DNA replicates – and eventually they are so short that they can’t protect the DNA and the cell is unable to divide. Stem cells and cancer cells have an enzyme called telomerase that replenishes the telomeres, keeping them nice and long so the cell can keep on dividing. Stem cells do eventually die – so technically, there are a limited number of cell divisions…but it’s a really, really big number. Cancer cells, on the other hand, are often totally immortal – they can just keep on dividing and dividing.

Another cool thing about stem cells is that they can give rise to many different kinds of cells. Here’s where things can get murky. There are stem cells in an embryo which are able to give rise to any of the cell types in the body: hepatocytes, epithelial cells, neurons, cardiac muscle cells…everything. This makes sense: if you’re going to grow into a human, you have to have cells that give rise to all the necessary cell types. These stem cells are called totipotent or pluripotent stem cells. There’s a slight difference between the two words: totipotent means that the stem cell can give rise to any and all human tissue cells – and it can even give rise to an entire functional human. The only totipotent cells in human development are the fertilized egg and the cells in the next few cell divisions.

After those few cell divisions, the cells become pluripotent. Pluripotent cells are similar to totipotent cells in that they can give rise to any and all human tissue cells. They’re different, though, because they are not capable of giving rise to an entire organism. On day four of development, the tiny little embryo forms two layers: one that will become the placenta and the other that will become the baby. The cells that will become the baby can give rise to any human tissue type (obviously) – but those cells alone can’t give rise to the entire organism (because you can’t form the baby without the placenta). Slight difference – but enough to make a separate term.

Another term you should know is multipotent. Multipotent stem cells cannot give rise to any old cell in the body – they are restricted to a limited range of cell types. For example, there are multipotent stem cells in the bone marrow that can give rise to red cells, white cells and platelets. They can’t give rise to hepatocytes, or any other cell type, though – so they are not totipotent or pluripotent.

There are lots of multipotent stem cells in the adult human body. They reside in the bone marrow, skin, muscle, GI tract, endothelium, and mesenchymal tissues. This means that there is a nice source for replacing cells that have died or been sloughed away.

What about myelodsyplasia?
So back to your question. Myelodysplasia is a hematopoietic disorder in which cells in the bone marrow grow funny (“dysplasia”) – they might be binucleate, or not have the normal number of granules, or whatever. In addition, some cases have an increase in blasts in the bone marrow – but not over 20%, or you’d call it an acute leukemia. Some cases transform, eventually, into an acute myeloid leukemia; others just stay the way they are and don’t become nasty.

Check out the image above, from a case of myelodysplasia. There is a bizarre, multinucleated erythroblast at 11 o’clock (this is called “dyserythropoiesis”, or disordered red cell growth). There are also two messed-up neutrophils (“dysgranulopoiesis”) at 4 o’clock and 10 o’clock – the one at 4 o’clock has only two nuclear lobes, and both are hypogranular (not enough specific granulation). There’s also an increase in blasts, if this field is representative: there’s one in the middle and (probably) one at 5 o’clock.

This disorder (actually, it’s a group of disorders) involves stem cells in the bone marrow. Sometimes only one cell line is involved (red cells, say); other times all three cell lines are involved (red cells, white cells and platelets). Either way, the disorder involves a stem cell, and since the stem cells in the bone marrow are multipotent, it would be correct to say that myelodysplasia is a disorder of multipotent stem cells in the bone marrow. It’s kind of redundant, though, because as far as we know, there aren’t any other kind of stem cells in the bone marrow! But at least you know the answer to your question now.