Question: Why does leukemia interest you? And why does MDS target certain cells, an after a while do all of the cells become 'infected' with MDS and at this stage, is their any way that this person can recover, also how and whyu do these people recover, and finally, what are some possible reasons why someone gets this disease, and do you have any leads on a cure or prevention? Thankyuo so so so so so much, i really really appreciate it. And i voted for you because you really inspired me!

This is the longest question ever! I’ll take the various questions in order.

First, leukemia interests me for a couple of reasons. I first got into it because it features “chromosomal translocations”, which are mutations involving whole chromosomes breaking and swapping positions with each other. The genetic outcome of this is the effect that the different context that genes at the breakpoint are exposed to, so if you find the breakpoint you can find the gene(s) responsible for the leukemia. I thought that was cool, and my PhD project was to map some of these breakpoints. The reason it is a good disease to study more broadly is that the nature of the disease allows us to do experiments that are much tougher in other cancers – you can collect samples at will from patients by bleeding rather than having to biopsy them (and the same is true of model mice with leukemia), and you can more easily transplant disease into mice, which allows you to do some very cool things. So leukemia research leads the way for all cancer research.

Cells that get MDS are blood stem cells, the rare cells that are “immortal” and have the ability to divide forever and produce all the different types of cells in the blood. Because immortality is an important property of leukemias, by targeting these stem cells, MDS has a head start. Once they become MDS cells, they grow much faster (and they die faster too, but their growth rate is faster than their death rate), so that they slowly take over the space which is occupied by all the normal cells. So the disease doesn’t “spread” to more cells, but the cells that are affected take over all of the space in the bone marrow by squeezing the normal cels out. Because the MDS stem cells don’t produce normal functional mature blood cells, this means that the person will have a reduced number of normal mature cells, which is why the symptoms of anemia and reduced immune function occur.

There is no spontaneous recovery from MDS, and the only cure that is known is a stem cell transplant – for this you need to have a matched donor, usually a relative, and then you irradiate the MDS patient to kill all of their stem cells and inject some stem cells that you take from the donor. This has a pretty good success rate, but only works if 1) you have a matched donor (a lot of people don’t) and 2) the patient is young enough to undergo transplant (irradiation is a very stressful procedure).

Most of the time people are treated with transfusions, which is just injecting blood from blood donors into MDS patients to reduce the anemia and restore immune function, but this is not permanent and needs to be done on a regular basis, so it is not a “cure”.

Why people get MDS is really unknown, but it is caused by mutations, and as far as we know these occur spontaneously as a normal part of cell division. When cells divide there are proof-readers to make sure there are no errors in the DNA, but sometimes some slip through, and that is where we think mutations come from (rather than some external cause, like chemical exposure).

My recent work suggests that the death of MDS cells might stimulate the remaining cells to divide faster, which means that their proof-readers will have to work harder, which means that they will make more mistakes, which means there will be more mutations and this leads to more aggressive leukemias. I have shown that if we can stop the cells from dying, the disease is much less severe and my mice live happily into old age. This is the opposite to what people have been trying to do – it is counter-intuitive to try and help the diseased cells survive – so the idea has encountered some resistance but I think it is solid and could lead to a new and better way of therapy!

Thanks for your enthusiasm, it is really fun to come on here and answer all of your questions like this. If you need a good PhD project when you finish university, look me up. 😉