With lymphoma, leukemia accounts for 50% of cancers observed in ataxia telangiectasia.

Once again, the central role of the ATM gene in the cell cycle is the most likely explanation (see The ATM gene").

Treatment of leukemia are constantly improving, for our young patients as well.

Leukemias are cancers characterized by abnormalities of white blood cell precursors in the bone marrow, with or without the presence in blood of abnormal cells.

Process in AT

---

The bone marrow is the site of production of all blood cells from stem cells:

• Red cells
• Platelets
• Precursors of white blood cells (different types of "babies" white blood cells that take their final function elsewhere).

• Radiation (X-rays, radioactivity ...)
• Chemicals (pesticides, fertilizers, benzene ...)
• Some medical treatments like chemotherapy and radiotherapy for an earlier and cancer.

But even if they do not constitutent the majority of cases of leukemia, we know that these factors generate DNA breaks in cells and in people with AT and the absence of ATM protein allows these abnormal cells to reproduce. This transformation mechanism is certainly highly contributory to the fact that these patients are prone to leukemia.

Diagnosis

---

We are talking about:

• Lymphocytic leukemia when the babies white cells involved were designed to give lymphocytes(B and T cells, see Immune system")
• Myeloid leukemia for the other cell lines
• Acute leukemia if the abnormality involves immature white blood cell precursors. In this case, the proliferation of cells is very rapid, leading rapidly to the onset of clinical signs of the disease
• Chronic leukemia if the abnormality does not affect the differentiation of precursors that can still differentiate into mature cells but whose function is abnormal. Typically, the symptoms may be delayed and evolution may be more indolent in the beginning.

Leukemia or lymphoma?

---

It may be noticed finally that the boundary between lymphoma and leukemia is not always very marked: in some non-Hodgkin's lymphoma, cells may be present in blood and certain aggressive lymphomas (lymphoblastic or Burkitt's lymphoma) may present an affected bone marrow and treated on a common treatment program to lymphomas and leukemias. Conversely, chronic lymphocytic leukemia are sometimes classified as lymphoma ... not easy to sort things out.

The mechanisms of malignant transformation are very similar and the main difference may be summarized as follows:

• acute leukemia (lymphoblastic): abnormality leading to blockage of maturation and abnormal accumulation by overgrowth of lymphocytes precursors that invade the bone marrow, hindering its functioning(reduction of other normal blood cells, red cells, unaffected white cells and platelets ) and sometimes also present in the circulating blood.
• chronic lymphocytic leukemia and non-Hodgkin lymphoma: abnormality leading to the accumulation of abnormal lymphocytes (usually B) but without abnormal differentiation. In chronic lymphocytic leukemia, accumulation occurs primarily in bone marrow and lymph nodes and abnormal lymphocytes are present in excess in the circulating blood. The normal bone marrow functioning is obstructed very late in the evolution that is generally very slow (lazy). In non-Hodgkin lymphoma accumulation is mainly in the lymph (and sometimes other organs) and more rarely in the bone marrow (and in this case abnormal cells can also be observed in blood but as a rule generally in small amounts).

Treatments

---

Children with AT are predisposed to acute lymphoblastic leukemia and chromosomal abnormalities on chromosome 14 are frequently observed (see Laboratory and Immunity and AT). The treatment of acute leukemia will be to destroy the degenerated cells by chemotherapy fairly strong. But this does not happen without collateral damage and the need to replenish a capital of healthy cells in the bone marrow may pass through a bone marrow transplant.
Generally speaking, treatments have results that are improving and can treat between 70 and 80% of patients. The problem in AT being the patient's hypersensitivity to chemotherapy, it is necessary to adapt the treatments, but conclusive results can be obtained. Non-Hodgkin lymphoma and Hodgkin's disease can be also treated with diverse but usually lighter chemotherapy often possible in day hospital. Sometimes, radiotherapy (radiation) is associated.

Radiation are among the causes that create DNA double-strand breaks in the nucleus of cells.

If these damaged cells multiply, cancer can develop. In reality, everything depends on the dose and repair capacity of the individual who receives it.

As people with ataxia telangiectasia can not repair these DNA breaks (see ATM: DNA controller), , this makes them extremely sensitive to radiation.

As for tobacco, pollution or other known carcinogens, special precautions can be taken to minimize the "radiation" risk.

Mode of action

---

Contrary to common belief, radiation is not only acting instantly by disintegration of the body it is going through, but mainly cause a destructive chemical reaction. This involves four steps:

1. Immediate physical phase: the energy of radiation causes the agitation of atoms and removes from them few electrons, forming ions.
2. Chemical phase: it may last a few seconds. Previously formed ions interact mainly with water, producing free radicals, especially oxidizing agents. These free radicals will then attack the cellular macromolecules, particularly DNA.
3. Biochemical phase: this is the phase where the repair mechanisms of the cell are switched on. One of these operates ATM, the protein encoded by the gene deficient in ataxia telangiectasia.
4. A phase named "biological": it concerns all the consequences of the actual conduct of the previous phase. These consequences are extremely varied and not all known. Different stages of cell reproduction can be blocked, the cells may die or reproduce with abnormalities and create cancers. The same dose of radiation can have very different biological consequences.

Radiation in our environment

---

We are literally overwhelmed by all kinds of radiation:

• {youtubejw}5Fj2LgCosu8{/youtubejw}
  Natural radiation: natural radioactivity of the earth, visible light, infrared, cosmic rays at high altitude, ultraviolet whose dangers are now well known.
• {dmotion}xbi9uc{/dmotion}
  Radiation from our modern environment: power lines, screens, computer networks (WLAN, Bluetooth), mobile phone network whose operators studies say they are harmless unlike independent studies (try to put your head in a microwave oven or face a radar that operate both substantially the same frequency as your mobile: after a while you'll get a little hot head) ...
• Medical devices radiation : X-rays and gamma used for diagnosis (radios and scanners) or for radiotherapy beams. As for the sun, the potential damage depends on the type, intensity and duration of exposure to radiation.

Radiation and medical machinery

---

Medical examinations using radiation are:

X-radiography ::
Although in recent years, the radiation doses used are less strong, "radio" is still a radiating mean of investigation. Unfortunately, in case of a trauma, radiography is often the most available and fastest way to make a diagnosis ... waiting for the system EOS.

Scanners (CT scan):
They also use X-rays, but at higher doses and can see more details of more body parts. But their limited number, the difficulty to implement them and the cost of each examination limits its use.

Scintigraphies:
They are also irradiating examinations as a radioactive liquid is injected to patients (gamma radiation). They allow to visualize the movement of fluids and to detect abnormal network as a blocked artery, the irrigation system of a cancer cluster ... (see Radiation and ionization")

Radiothérapy:
Like chemotherapy, radiotherapy is intended to cause self-destruction (apoptosis - see cell cycle in The ATM gene") of cancer cells by breaking DNA molecules of these cells with high radiation (the chemotherapies are doing the same but by chemically interfering with DNA). They can be administered from outside the body by bombarding the affected area, or inside by placing a radioactive source closer to the tumor.

Problem: in one as in the other case and regarding the current state of the care centers equipment, nearby healthy cells are also affected. The normal healing of surrounding tissue can recover from these injuries, while cancer cells are unable to recover. That explains the differential effect of cancer treatment between healthy and diseased tissues and ultimately their usefulness in the treatment of these diseases.
However, in inducing DNA breaks, chemotherapy as radiation are mutagenic, that is to say they can induce long-term occurrence of mutations in DNA, some of which may accumulate and lead to the development of secondary cancers.

Patients suffering from AT, due to the genetic defect that leads to defective function of the ATM protein, increase the toxicity of anticancer treatment on these two aspects. Normal and immediate damage on healthy cells affected by chemotherapy or radiotherapy "heal" slower and less well as they would in the absence of ATM default. This has the effect of an acute toxicity (normal and transient decrease of white blood cells and platelets after these treatments may be more marked and more prolonged, leading to a higher risk of infection and bleeding ).

In addition, ATM also playing a role in DNA repair by preventing the accumulation of mutations, the patients with AT exposed to chemotherapy or radiotherapy will have a greater risk of mutations associated with these treatments. The risk of developing secondary cancers is higher.

Despite all the advances that promise that these techniques will still be used for a long time (see Radiation and ionization"), awareness of the potential harmful effects of radiation led to development of exams not irradiating or so little that the amount of radiation used is negligible. They are:

EOS
EOS is a radiography system developed from the work of French Nobel laureate in physics Georges Charpak. It uses X-radiation at very low level to reconstruct the 3D skeleton. (See Radiation and ionization")

Details

Written by Acknowledgement: Dr F. Suarez, oncologist, Necker, Paris

Last Updated: 12 November 2011