Monday, April 23, 2012

Cigarette smoking and acute myeloid leukemia (AML)

What is acute myeloid leukemia (AML)?

Acute myeloid leukemia (AML) goes by many names, including acute myelocytic leukemia, acute myelogenous leukemia, acute granulocytic leukemia, and acute non-lymphocytic leukemia. "Acute" means that the leukemia can grow quickly, and if not treated, could be fatal in a few months.

Acute myeloid leukemia (AML) is a disorder of the process that normally produces neutrophils, a type of white blood cell. Neutrophils fight infections caused by bacteria. Mature neutrophils develop from immature (undeveloped) white blood cells in a process called differentiation. The production of mature neutrophils usually is highly regulated. For example, the body rapidly makes more neutrophils during an infection and returns to a regular level of production when the infection is controlled.

AML is a cancer that starts in the cells that are supposed to mature into different types of blood cells. AML starts in the bone marrow (the soft inner part of the bones, where new blood cells are made), but in most cases it quickly moves into the blood. It can sometimes spread to other parts of the body, including the lymph nodes, liver, spleen, central nervous system (brain and spinal cord), and testicles (in men). In contrast, other types of cancer can start in these organs and then spread to the bone marrow (or other places). Those cancers are not leukemia.

The American Cancer Society's most recent estimates for acute myeloid leukemia (AML) cancer in the United States are for 2010:
  • About 12,300 new cases of AML (Most will be in adults)
  • About 8,950 deaths from AML (Almost all will be in adults)

The average age of a patient with AML is about 67. AML is slightly more common among men than among women. The lifetime risk of getting AML for the average man is about 1 in 250. For the average woman the risk is about 1 in 300.

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Link between Cigarette Smoking and acute myeloid leukemia (AML)

Multiple scientific studies found causal links between cigarette smoking habits and risks for acute myelogenous leukemia (AML) development, mostly due to the chemical benzene.

Benzene is a colorless and sweet smelling chemical found in numerous modern life compounds, like gasoline, industrial solvents, or cigarettes. In general, cigarettes release between 50 and 150 micrograms of benzene per cigarette, thus elevating the risk of the AML development for all tobacco smokers. It was found that the average smoker consumes just under two milligrams of benzene every day, which is about 10 times the average daily intake of a nonsmoker.

The benzene itself is not present in the tobacco, but is produced during the burning process. Studies show that benzene is rapidly absorbed through the lungs during inhalation. Overall, approximately one half of the benzene is inhaled into the lungs, where it is then distributed to different parts of the body, including fatty tissue and bone marrow.

Although an statistical data for the higher risks of AML development for cigarette smokers is not uniform, based on the particular researches settings, the majority of studies in the last 20 years have reported a statistically significant, moderate relationship with a relative risk of about 1.4 for AML among cigarette smokers compared to non-smokers and the relative risk approaching 2.0 for heavy smokers.

The controversial findings in the statistically significant causal relationship might be driven by the fact that smoking may contribute to the particular types of the leukemia, while not affecting others.

The French-American-British (FAB) traditional classification for describing AML morphology, lists 9 types of AML:

M0: Myeloblastic without differentiation
M1: Myeloblastic without maturation
M2: Myeloblastic with maturation
M3: Promyelocytic
M4: Myelomonocytic
M5a: Monocytic without differentiation (monoblastic)
M5b: Monocytic with differentiation
M6: Erythroleukemic
M7: Megakaryocytic

Dr. Janice M. Pogoda of the University of Southern California in Los Angeles, and colleagues performed investigation, looking for the correlation between smoking and particular AML subtypes. They found out that smoking plays very significant role in M2 subtype, but not in others. Indeed, smoking may be responsible for roughly 42% of cases of this subtype of leukemia, reported the researchers.

The results confirmed that while smokers in general were 2.3 times more likely to develop M2 type AML, older adults aged 60 to 75 years were at 3.3 times greater risk of developing this illness.

Those who smoked for more than 35 years and smoked unfiltered cigarettes showed the highest risk, but even older adults who smoked filtered cigarettes still had a nearly threefold higher risk compared with nonsmokers.

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Other Risk Factors

There are a few known risk factors for acute myeloid leukemia, apart from cigarette smoking.
  • Chemicals. Exposure to certain chemicals has been linked to acute leukemia. For instance, long-term exposure to high levels of benzene from different sources is a risk factor for acute myeloid leukemia. Benzene is a solvent used in cleaning, in some industrial processes for drugs, plastics, dyes, gasoline, and other goods. Patients with other cancers who are treated with certain chemotherapy drugs are more likely to develop AML. Using these drugs along with radiation treatment further increases the risk.
  • Radiation. Exposure to a high dose of radiation exposure is a risk factor for acute myeloid leukemia. People who survived the atomic bomb in Japan had a greatly increased risk of getting acute leukemia, most within six to eight years. The risk of leukemia from lower levels of radiation, such as from radiation treatment, X-rays, or CT scans, is not clear.
  • Certain blood problems. Patients with certain blood problems seem to be at a higher risk for getting acute myeloid leukemia. If your body makes too many red cells or not enough platelets, for instance, this may raise your risk. Some people with chronic myelogenous leukemia (CML — another type of leukemia) later develop a form of AML. The risk of getting AML is higher if treatment for these other blood problems includes some types of chemotherapy or radiation.
  • Congenital (present at birth) syndromes. For the most part, AML does not appear to be an inherited disease. It is rare for it to run in families, so a person's risk is not usually increased if a family member has the disease. But there are some congenital syndromes with genetic changes that seem to raise the risk of AML. These include:
·         Down syndrome
·         Fanconi anemia
·         Bloom syndrome
·         ataxia-telangiectasia
·         Blackfan-Diamond syndrome
  • Gender. AML is more common in males than in females. The reasons for this are not clear.

AML Symptoms

The symptoms of AML are caused by low numbers of healthy blood cells and high numbers of leukemia cells.
  • White blood cells fight infection. Low numbers can lead to fever and frequent infections.
  • Red blood cells carry oxygen throughout the body. Low numbers can lead to anemia — feeling tired or weak, being short of breath and looking pale.
  • Platelets control bleeding. Low numbers can lead to easy bleeding or bruising and tiny red spots under the skin (petechiae).
  • High numbers of leukemia cells may cause pain in the bones or joints.
A person with AML may feel generally unwell and run-down. He or she may also have other, less common symptoms.

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