Leukaemia, bone marrow and blood cells

Leukaemia is a type of blood cancer that originates in the blood cells found in the bone marrow. There are many different types of leukaemia that can affect both children and adults. Each type of leukaemia can affect a specific cell group and has different treatments and prognoses. In general, we refer to acute leukaemias as those with an aggressive course, and chronic leukaemias as those in which the affected cells proliferate more slowly.

Leukaemia causes an uncontrolled increase in white blood cells. These cancerous cells infiltrate the bone marrow and prevent the other of the blood cells — healthy red blood cells, platelets and white blood cells or leukocytes — from forming properly.

Thus, among other characteristic symptoms may appear, including marked tiredness associated with anaemia due to poor red blood cell production; haemorrhages or petechiae, due to insufficient platelet production; and susceptibility to infections, due to the dysfunction of leukocytes, event thought their numbers may be elevated.

In Spain, according to data from the SEOM, the Spanish Society of Medical Oncology, around 6,000 new cases of leukaemia are diagnosed each year. Of these, about 350 cases occur in children. Leukaemia is the most common cancer in the paediatric age group, as 30% of the neoplasms diagnosed in children are leukaemias. The most common type of leukaemia, its treatment and prognosis differ according to age.

Leukaemia is not the only blood cancer. In fact, it is not the most common either. In Spain, more than 10,000 different lymphomas, more than 3,000 cases of multiple myeloma and around 3,000 myelodysplastic syndromes are diagnosed each year.

Recommended materials:

What is leukaemia? Ted Lessons. Danilo Alegra and Dania Puggioni

Marrow: the factory of life. Dr. Helena Alves. Portugal.

The bone marrow is the body’s ‘blood factory’.

Bone marrow is a spongy tissue found inside some of the bones of the body such as the iliac crests (hip bone), the sternum or the bones forming the skull. In colloquial language it is called “marrow”. It should not be mistaken for the spinal cord as they have nothing to do with each other. Their functions are totally different. The spinal cord is located in the spinal column and transmits nerve impulses from the brain to the entire body and vice versa.

Bone marrow is a factory where immature cells called blood stem cells, or haematopoietic stem cells, are produced. These cells divide to create more cells, which will give rise to all the cells in the blood. The three most important are: white blood cells, or leukocytes, which defend us against infections; red blood cells, or haematids, which transport oxygen around the body; and platelets, which help the blood to clot.

Blood stem cells from a healthy person can be transplanted in some cases to treat acute leukaemias, aggressive lymphomas or patients who do not respond well to treatment.

See Bone marrow, peripheral blood or umbilical cord blood transplantation

Blood is made up of a fluid called plasma and three major types of cells, each of which performs a specific function.

The red blood cells, also called haematids or erythrocytes, are the cells responsible for transporting oxygen from the lungs to the tissues, and for carrying carbon dioxide from the tissues back to the lungs for expulsion. Like other blood cells, they are produced in the bone marrow. Red blood cells give blood its characteristic red colour. The red blood cell count can be assessed in blood tests. Anaemia occurs when the body’s red blood cell levels are below normal. When there are insufficient red blood cells, parts of the body do not receive sufficient oxygen and, as a result, cannot function as they should, thus leading to problems. In a healthy organism, hundreds of billions of red blood cells are produced every day!

White blood cells or leukocytes are the body’s defence against infection and foreign substances that may enter the body. To defend the body properly, there needs to be a sufficient number of white blood cells capable of responding adequately, reaching the place where they are needed, and then destroying and digesting harmful micro-organisms and substances. Like all blood cells, white blood cells are produced in the bone marrow. They are formed from precursor cells (stem cells) that mature into one of the five main types of white blood cells: neutrophils, lymphocytes, monocytes, eosinophils and basophils. A person produces approximately 100 billion white blood cells per day. If white blood cell production decreases, the patient is more prone to infections.

Platelets or thrombocytes help blood to clot when a blood vessel ruptures. They help produce blood clots to slow or stop bleeding and to facilitate wound healing.

When the amount of platelets is insufficient, the blood cannot clot as it should, resulting in an increased risk of bleeding. This condition is called thrombocytopaenia. In this situation, bruising or petechiae may also appear: petechiae are small red spots that appear spontaneously on the skin. Thrombocytopaenia means that you have fewer than 150,000 platelets per microlitre of circulating blood. Because each platelet lives for around 10 days only, your body normally renews its supply of platelets continuously by producing new platelets in the bone marrow.

All blood cells in the bone marrow are the result of differentiation and maturation of stem cells, and are often collectively referred to as haematopoietic progenitors.

Under normal conditions, the production of blood cells takes place in a controlled manner, as the body needs them. The alteration of this balance can lead to various diseases; some are due to an insufficient production of all blood cells (marrow aplasia) or of a specific type of blood cell (erythroblastopaenia, amegakaryocytosis, agranulocytosis); others are caused by the production of cells incapable of carrying out their own functions and in insufficient quantities (myelodysplastic syndromes) and finally, others are due to the production of cancer cells in large numbers (leukaemias, thrombocythaemia or polycythaemia).

Despite all the advances and relentless research, the causes of leukaemia remain unknown. The incidence is known to be higher in males than in females, and in terms of race, white people have a greater prevalence than black people. However, it is not yet possible to provide a clear explanation as to why some people develop the disease while others do not.

Through the study of a large number of cases, it has been possible to establish certain risk factors that may favour the development of this disorder. For example, exposure to large doses of high-energy radiation, such as from the atomic bomb explosions in Japan during World War II, or from accidents at nuclear power plants, increases the risk of developing leukaemia. Therefore, in nuclear power plants, strict safety standards are in place to protect workers and the public from exposure to harmful radiation. In contrast, no correlation has ever been found between electromagnetic radiation (mobile phones, telephone and radio antennas, etc.) and the development of leukaemia.

Some genetic characteristics may increase the risk of developing leukaemia. One of these characteristics are Down syndrome, Li-Fraumeni syndrome or Fanconi anaemia. Children born with these syndromes are more susceptible to the disease.

Furthermore, exposure to certain chemicals, such as benzene, over long periods of time may also be a risk factor. Treatments used to fight other types of cancer can also increase the patient’s risk of developing leukaemia. However, the latter factor represents a minimal risk compared to the benefits of chemotherapy.

In recent years, research has begun to identify forms of familial predisposition to leukaemia, that is, inherited genetic alterations that may increase the risk of developing the disease. These advances do not mean that leukaemia is hereditary in most cases, but they do open the door to better diagnosis, personalised monitoring and prevention in families at higher risk.

As scientific research into leukaemia continues, new and better ways of treatment are being discovered and the chances of a cure continue to increase. Nevertheless, it is normal for both patients and their families to be concerned about the future.

With the aim of one day making leukaemia a 100% curable disease and to improve the quality of life of patients, in 2010 the Josep Carreras Foundation launched the Josep Carreras Leukaemia Research Institute. This Institute is the first in Spain to carry out research exclusively on haematological malignancies and one of the largest centres of its kind in Europe.

The prognosis of leukaemia is not the same in all cases. It depends largely on the genetic alterations present in the leukaemic cells. Some abnormalities allow the disease to respond very well to treatment, while others make it more resistant. Survival averages and other types of statistics are sometimes used to try to elucidate whether a given patient will be able to overcome the disease. However, it is important to remember that statistics and averages are calculated from a large number of cases and cannot be used to predict the evolution of a specific patient, as no two patients are the same, and responses to treatment can vary greatly from one patient to another.

Thus, cure rates can range from 90% in certain types of acute myeloblastic leukaemia — promyelocytic leukaemia — or in childhood acute lymphoblastic leukaemias, to less than 20% in leukaemias associated with previous diseases or treatments received in the past. The haematologist responsible for the patient’s care is best placed to assess each patient’s prognosis, although even for specialists, the final course of the disease cannot always be predicted.

Cancer outcomes are often expressed according to how many people are still alive 5 years after diagnosis and treatment. This is why it is common to read “5-year survival”. This concept does not mean that a person will only live 5 years, but rather indicates the percentage of patients who have lived 5 years or more according to studies. Many people live much longer after achieving remission and, in general, most relapses occur within the first 5 years after completing treatment. When a patient remains in remission during this period, the risk of the disease returning is low.

For this reason, doctors usually refers to survival or remission rather than cure, since in some cases the disease may reappear even after responding well to treatment.

Complete remission is considered to have been achieved when leukaemia can no longer be detected using standard tests and there are no signs or symptoms of the disease. In this context, the term “no evidence of disease” is also used. However, we now know that small amounts of leukaemic cells may remain, invisible under the microscope. This is known as mesurable residual disease (MRD), and its detection using highly sensitive techniques makes it possible to assess the risk of relapse more accurately and better adapt treatments.

In partial remission, by contrast, some signs and symptoms have disappeared, but the disease has not disappeared completely.

DNA, or deoxyribonucleic acid, is a complex protein found in the nucleus of every cell in our body. This is information that is inherited in living beings. Almost every cell in the body has the same DNA code. The order and sequence of this code determines all the information the organism needs to form and maintain a healthy condition. Like the alphabet, their order and composition can form letters, words and sentences.

An important property of DNA is that it can replicate or make copies of itself. Each strand of DNA in the double helix can serve as a template for duplicating the sequence of bases. This is essential when cells divide, because each new cell needs to have an exact copy of the DNA present in the original cell. The DNA inside each cell is in long strands called chromosomes. Every time a cell divides into two new cells, it has to make a new copy of its chromosomes. This process is not perfect and errors can occur, such errors affect the genes contained in the chromosomes.

A gene is the unit of information at a locus (fixed position on a chromosome) in the DNA. Genes are small pieces of DNA. Genes influence a person’s risk of developing some diseases and conditions. Each of us has around 24,000 different types of genes.

Genes that help cells to grow, divide or stay alive are called oncogenes. Genes that help maintain control of cell division or cause cells to die at the right time are called tumour suppressor genes.

There are several types of chromosome changes that can be found in the cells of some types of leukaemia:

• • • • Translocations are the most common types of chromosomal changes. It means that a part of one chromosome breaks off and attaches to a different chromosome. At the point of this detachment, genes can be activated or deactivated. As if a part of a book in a library were to attach itself to another book.
      • Deletions occur when part of a chromosome has been lost. In this loss, a gene that helped keep cell growth in check may no longer be present. As if a part of a book were to have been lost.
      • Inversions occur when a part of the chromosome is presented, but in an inverted order. It can also cause the loss of a gene because the cell can no longer read its instructions. As if a book were upside down in a library.
      • A duplication or addition occurs when there is a copy of part or all of a chromosome. This can lead to the generation of too many copies of a gene within a cell. As if there were several repeated chapters within a book.

Leukaemia can develop when a mutation occurs in the DNA of a blood cell. These genetic changes may affect one or more genes, involve the loss of genes, or cause rearrangements of genes or entire chromosomes. Although the body can repair many of the mutations that arise every day, in leukaemia these mechanisms fail and control over cell growth and division is lost. As a result, mutated and immature cells grow out of control, invade the bone marrow and displace healthy cells from the bloodstream.

Leukaemia is not considered a hereditary disease, but some people may inherit DNA mutations from one of their parents that increase their risk of developing it — known as hereditary or germline predisposition. There is currently a great deal of research devoted to better understanding these genetic factors and to improving the diagnosis and monitoring of families at higher risk.

In most cases, mutations related to leukaemia are acquired after conception. Some may even appear during pregnancy, although this is rare. In adults, most of these genetic changes occur throughout life, are usually random events with no clear cause, and become more frequent with ageing.