What is leukemia?

I am in the process of writing a chapter on CLL for a new textbook and I thought I would take the opportunity to write a guide to CLL for patients and their carers alongside. This has been a long term ambition of mine. I will publish each section on my blog as it is written, and then when it is finished I will endeavor to get the whole thing published as a booklet.

Let us start with the question, “What is leukemia?”

Literally, it means “white blood” and the name was coined in 1846 by Rudolf Virchow, the famous German physician and politician. It means that there is an excess of white blood cells in the blood. Now, there are lots of reasons for having too many white cells in the blood, the most common being an infection. White cells are principally there to fight infections and when you have an infection the usual thing is for the body to make more white cells to combat it. However, in a leukemia the cells are growing spontaneously without stimulation. Moreover, they all derive from single cell that has lost part of its control mechanism. The word “monoclonal” describes it – it simply means that all the cells of the leukemia have the same grandparent. Virchow himself taught the then novel concept that every living cell derives from another similar cell.

(As an aside I must tell you a funny story about Virchow. It is said that Otto von Bismarck, the German Chancellor, challenged Virchow to a duel. Virchow, as the challenged party had the choice of weapons and he chose two sausages, one of which had been inoculated with cholera. Bismarck is said to have called off the duel at once.)

Simply put there are four types of leukemia, two myeloid and two lymphoid, and two acute and two chronic; thus: acute myeloid leukemia, chronic myeloid leukemia, acute lymphoid leukemia and chronic lymphoid leukemia. The acute leukemias are usually called “blastic” and the chronic leukaemias “cytic”; hence: acute myeloblastic leukemia, chronic lymphocytic leukemia and so on. Of course, this is a gross oversimplification and there are many subdivisions. The latest WHO manual describes 62 different types of leukemia.

Chronic lymphocytic leukemia (CLL) is the commonest of them (at least in Europe and North America). But to make things more complicated CLL is also classified amongst the lymphomas, so what is a lymphoma?

A lymphoma is a tumor of lymphocytes. The word ‘tumor’ is a bit misleading. Originally it meant a swelling, so if you knocked you head and raised a lump, it could be called a tumor on your head, and in Victorian times it probably was. Gradually, though, words change their meanings and ‘tumor’ now means the same as the lay-term ‘growth’ or the medical euphemism ‘neoplasm’. Such growths can be benign, but most of the tumors we talk about are malignant, so the stark term ‘cancer’ is another synonym. A lymphoma can be thought of as a cancer of the lymph glands – though for several reasons even this can be misleading.

There are even more types of lymphomas than there are leukemias. The WHO handbook lists 84! Some of them are as rare as toads with wooden legs, but CLL is one of the commonest. When viewed as a lymphoma, CLL is often called small lymphocytic lymphoma, SLL. You would only use the term clinically if there was no increase in lymphocytes in the peripheral blood, but one or more lymph glands is enlarged. Other than this there is no difference between CLL and SLL; by every other criterion they are the same disease.

I need to clear up a few more misconceptions in this first section. I have used the term “lymph gland” because that is what they are often called, but strictly speaking they are not glands at all. When you have a sore throat your doctor may say to you “Your glands are up.” So it isn’t only the lay-public that engages in this fiction. A better term is “lymph node”.

The lymphoid system is spread throughout the body and is represented mainly by the bone marrow, the thymus, the spleen and the lymph nodes, (although there are important local systems in the gut - especially the appendix - and in the skin). Its purpose is defense against intruders, chiefly various types of germs. You don’t keep your defense forces at home in their barracks; you send them out on patrol. Similarly, lymphocytes are sent wandering all over the body; there is hardly a tissue where you would be unlikely to encounter a lymphocyte. Sometimes they do their patrolling along the main highways – arteries and veins – but they also have access to special routes, what you might think of as highways restricted for military use. These small lymph vessels are called “lymphatics”. Set along the lymphatics are little way-stations where the lymphocytes rest and recuperate, communicate with other cells and take instruction. These are the lymph nodes.

We also need to distinguish between the terms “benign” and “malignant”. A malignant growth is one outside the bounds of control. Normally a cell grows according to a specific stimulus and dies when given a different stimulation. It sticks with its fellows. A pancreas cell doesn’t suddenly take off to see what it would be like to live in the lung. It is restricted by tissue planes – a live cell grows up to the capsule of the liver, but it doesn’t breach it. A benign tumor may grow in an out of control way, but it doesn’t breach boundaries. However, a malignant cell accepts no restrictions. It invades into other tissues and goes walkabout to settle in other organs – this is called metastasis. Once it has spread it is still the original tumor, so if a breast cancer spreads to the liver it is still secondary breast cancer in the liver, not liver cancer,

Is CLL a benign or malignant tumor? That’s a difficult one. In that is only goes where lymphocytes normally go, it may be thought benign, but it does cross tissue boundaries to some degree. There are other types of cancer which come somewhere in the middle between benign and malignant; basal cell carcinoma is one. It certainly invades locally (its other name is rodent ulcer) but it seldom metastasizes.

Tomorrow we’ll think about where the CLL cell comes from.