Thursday, December 13, 2007

Medical Ignorance - T-cells and the Thymus

I have not posted on ALL science for a long time as I thought I had investigated and written about as much as I needed to, that I could understand and that I could try to communicate to others.

I subscribe to the email notification service of BioMed Central for oncology papers. Most are nothing to do with leukaemia but I came across this open-access paper, Gene expression profiling of leukaemic cells and primary thymocytes predicts a signature for apoptotic sensitivity to glucocorticoids, published in November this year.

And I was stunned by a major gap in my ignorance. However, I am also stunned at how recent the science I describe below is.

In the foetus and up to puberty white blood cell T-cell lymphocytes are produced in an organ called the thymus located in the upper chest, not in the bone marrow. In a normally functioning thymus the T-cells are filtered - good from defective, and the defective ones are killed off (apoptosis). Not until 1961 was the importance of the thymus realised - previously a thymus would be surgically removed with a resulting loss of lymphocytes and immunity!

When the T-cell precursors are in the thymus, forming an integral part of its structure, they are known as thymocytes.

The T-cells migrate to other organs (principally the spleen, lymph nodes and bone marrow) and the blood. Gradually, T-cell reproduction is, at puberty, transferred from the thymus to the bone marrow, lymph nodes and spleen and the thymus gradually becomes a redundant mass of fatty tissue.

In childhood T-cell Acute Lymphoblastic Leukaemia the thymus is pushing out loads of T-cell lymphocyte precursors (or as they are referred to in science, progenitors) known as lymphoblasts, not mature T-cell lymphocytes. This is the key to diagnosis - levels of lymphoblasts in the blood and bone marrow.

However, it is seemingly not the fault of the thymus.

The progenitors of the lymphoblasts and lymphocytes are stem cells produced in the bone marrow. Stem cells come in a variety of flavours. Our famous embryonic stem cells can differentiate into whatever part of the body they like - heart, liver, kidney, skin etc. Then they become body-part specific stem cells but some are seemingly multifuctional (interesting research was announced on Friday into using skin stem cells to cure the blood disorder Sickle Cell Anaemia).

Some become blood (hematopoietic) stem cells - those destined to become B-cell lymphocytes stay in the bone marrow, and those to be metamorphosised into T-cell lymphocytes find their way by blood to the Thymus.

Recent research into the roll of leukaemic stem cells (and when I say recent I mean this decade) has been focussed on Acute Myeloblastic Leukaemia rather than B or T-cell Lymphoblastic Leukaemia but malformed stem cells do seem to be the "culprit" in all leukaemias.

Genetically-malformed hematopoetic stem cells cannot be processed into full-blown T-cell lymphocytes but remain as T-cell lymphoblasts. It would seem that the thymus is unable to distinguish between good and bad stem cells, the progenitors, but can distinguish between good and bad product derived from good raw material. If it receives bad raw material and produces excess lymphoblasts, it won't kill off the bad cells.

At the end of the day the thymus (a factory) is pretty dumb!

The leukaemic stem cells are apparently not very receptive to chemotherapy drugs.

So I will worry.

P.S. Obviously, and as always, this is a lay-person's explanation in both its writing and its reading - if any of my science is erroneous or just slightly "fucked up", then please correct me either through the Comments or by email.

I'll try and get on to Dexamethasone and thymocytes in our next scientific post - hopefully, before I go back to the UK for Christmas.


Lea White said...

Wow, what an interesting article!

Anonymous said...

I'm looking foward to your views on Dex and have hugh sympathy for both your wife and daughter looking at the tantrum photograph you posted.

During the heavy blocks of Dex administered earlier in the treatment, I would say that Leonie experienced nearly autistic characteristcs, hours of sitting alone doing very elaborate colouring, no physical or emotinal contact and unexplained mixing up of words. Then there would be the occasional hyper outbursts. I do think that Dex really hits the children very hard. The present dose of Dex results in her feeling very sad, impatient and emotional. The worst part is she keeps asking am I off the Dex yet ? She is aware, even at 5 years of age of the effect it has on her. I would go as far as to say that it causes depression in children.

However, if she annoys her brother or sister at any time they ask her sarcastically are you on Dex ?