Leukemia is a type of cancer of the
blood or bone marrow characterized by an abnormal increase of white
blood cells. Leukemia is a broad term covering a spectrum of diseases.
In turn, it is part of the even broader group of diseases called
hematological neoplasms.
Clinically and pathologically,
leukemia is subdivided into a variety of large groups. The first
division is between its acute and chronic forms:
- Acute leukemia is characterized by a rapid increase in the numbers of immature blood cells. Crowding due to such cells makes the bone marrow unable to produce healthy blood cells. Immediate treatment is required in acute leukemia due to the rapid progression and accumulation of the malignant cells, which then spill over into the bloodstream and spread to other organs of the body. Acute forms of leukemia are the most common forms of leukemia in children.
- Chronic leukemia is characterized by the excessive build up of relatively mature, but still abnormal, white blood cells. Typically taking months or years to progress, the cells are produced at a much higher rate than normal cells, resulting in many abnormal white blood cells in the blood. Whereas acute leukemia must be treated immediately, chronic forms are sometimes monitored for some time before treatment to ensure maximum effectiveness of therapy. Chronic leukemia mostly occurs in older people, but can theoretically occur in any age group.
Additionally,
the diseases are subdivided according to which kind of blood cell is
affected. This split divides leukemias into lymphoblastic or lymphocytic
leukemias and myeloid or myelogenous leukemias:
- In lymphoblastic or lymphocytic leukemias, the cancerous change takes place in a type of marrow cell that normally goes on to form lymphocytes, which are infection-fighting immune system cells. Most lymphocytic leukemias involve a specific subtype of lymphocyte, the B cell.
- In myeloid or myelogenous leukemias, the cancerous change takes place in a type of marrow cell that normally goes on to form red blood cells, some other types of white cells, and platelets.
Combining
these two classifications provides a total of four main categories.
Within each of these four main categories, there are typically several
subcategories. Finally, some rarer types are usually considered to be
outside of this classification scheme.
- Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in young children. This disease also affects adults, especially those age 65 and older. Standard treatments involve chemotherapy and radiation. The survival rates vary by age: 85% in children and 50% in adults. Subtypes include precursor B acute lymphoblastic leukemia, precursor T acute lymphoblastic leukemia, Burkitt's leukemia, and acute biphenotypic leukemia.
- Chronic lymphocytic leukemia (CLL) most often affects adults over the age of 55. It sometimes occurs in younger adults, but it almost never affects children. Two-thirds of affected people are men. The five-year survival rate is 75%. It is incurable, but there are many effective treatments. One subtype is B-cell prolymphocytic leukemia, a more aggressive disease.
- Acute myelogenous leukemia (AML) occurs more commonly in adults than in children, and more commonly in men than women. AML is treated with chemotherapy. The five-year survival rate is 40%. Subtypes of AML include acute promyelocytic leukemia, acute myeloblastic leukemia, and acute megakaryoblastic leukemia.
- Chronic myelogenous leukemia (CML) occurs mainly in adults. A very small number of children also develop this disease. Treatment is with imatinib (Gleevec in US, Glivec in Europe) or other drugs. The five-year survival rate is 90%. One subtype is chronic monocytic leukemia.
- Hairy cell leukemia (HCL) is sometimes considered a subset of CLL, but does not fit neatly into this pattern. About 80% of affected people are adult men. There are no reported cases in young children. HCL is incurable, but easily treatable. Survival is 96% to 100% at ten years.
- T-cell prolymphocytic leukemia (T-PLL) is a very rare and aggressive leukemia affecting adults; somewhat more men than women are diagnosed with this disease. Despite its overall rarity, it is also the most common type of mature T cell leukemia; nearly all other leukemias involve B cells. It is difficult to treat, and the median survival is measured in months.
- Large granular lymphocytic leukemia may involve either T-cells or NK cells; like hairy cell leukemia, which involves solely B cells, it is a rare and indolent (not aggressive) leukemia.
- Adult T-cell leukemia is caused by human T-lymphotropic virus (HTLV), a virus similar to HIV. Like HIV, HTLV infects CD4+ T-cells and replicates within them; however, unlike HIV, it does not destroy them. Instead, HTLV "immortalizes" the infected T-cells, giving them the ability to proliferate abnormally.
Damage
to the bone marrow, by way of displacing the normal bone marrow cells
with higher numbers of immature white blood cells, results in a lack of
blood platelets, which are important in the blood clotting process. This
means people with leukemia may easily become bruised, bleed
excessively, or develop pinprick bleeds (petechiae).
White blood cells, which are
involved in fighting pathogens, may be suppressed or dysfunctional. This
could cause the patient's immune system to be unable to fight off a
simple infection or to start attacking other body cells. Because
leukemia prevents the immune system from working normally, some patients
experience frequent infection, ranging from infected tonsils, sores in
the mouth, or diarrhea to life-threatening pneumonia or opportunistic
infections.
Finally, the red blood cell deficiency leads to anemia, which may cause dyspnea and pallor.
Some patients experience other
symptoms, such as feeling sick, having fevers, chills, night sweats and
other flu-like symptoms, or feeling fatigued. Some patients experience
nausea or a feeling of fullness due to an enlarged liver and spleen;
this can result in unintentional weight loss. If the leukemic cells
invade the central nervous system, then neurological symptoms (notably
headaches) can occur. All symptoms associated with leukemia can be
attributed to other diseases. Consequently, leukemia is always diagnosed
through medical tests.
The word leukemia, which means
'white blood', is derived from the disease's namesake high white blood
cell counts that most leukemia patients have before treatment. The high
number of white blood cells are apparent when a blood sample is viewed
under a microscope. Frequently, these extra white blood cells are
immature or dysfunctional. The excessive number of cells can also
interfere with the level of other cells, causing a harmful imbalance in
the blood count.
Some leukemia patients do not
have high white blood cell counts visible during a regular blood count.
This less-common condition is called aleukemia. The bone marrow still
contains cancerous white blood cells which disrupt the normal production
of blood cells, but they remain in the marrow instead of entering the
bloodstream, where they would be visible in a blood test. For an
aleukemic patient, the white blood cell counts in the bloodstream can be
normal or low. Aleukemia can occur in any of the four major types of
leukemia, and is particularly common in hairy cell leukemia.
No single known cause for all of
the different types of leukemia exists. The known causes, which are not
generally factors within the control of the average person, account for
relatively few cases. The different leukemias likely have different
causes.
Leukemia, like other cancers,
results from somatic mutations in the DNA. Certain mutations produce
leukemia by activating oncogenes or deactivating tumor suppressor genes,
and thereby disrupting the regulation of cell death, differentiation or
division. These mutations may occur spontaneously or as a result of
exposure to radiation or carcinogenic substances, and are likely to be
influenced by genetic factors.
Among adults, the known causes
are natural and artificial ionizing radiation, a few viruses such as
Human T-lymphotropic virus, and some chemicals, notably benzene and
alkylating chemotherapy agents for previous malignancies. Use of tobacco
is associated with a small increase in the risk of developing acute
myeloid leukemia in adults. Cohort and case-control studies have linked
exposure to some petrochemicals and hair dyes to the development of some
forms of leukemia. A few cases of maternal-fetal transmission have been
reported. Diet has very limited or no effect, although eating more
vegetables may confer a small protective benefit.
Viruses have also been linked to
some forms of leukemia. Experiments on mice and other mammals have
demonstrated the relevance of retroviruses in leukemia, and human
retroviruses have also been identified. The first human retrovirus
identified was Human T-lymphotropic virus, or HTLV-1, is known to cause
adult T-cell leukemia.
Some people have a genetic
predisposition towards developing leukemia. This predisposition is
demonstrated by family histories and twin studies. The affected people
may have a single gene or multiple genes in common. In some cases,
families tend to develop the same kind of leukemia as other members; in
other families, affected people may develop different forms of leukemia
or related blood cancers.
In addition to these genetic
issues, people with chromosomal abnormalities or certain other genetic
conditions have a greater risk of leukemia. For example, people with
Down syndrome have a significantly increased risk of developing forms of
acute leukemia (especially acute myeloid leukemia), and Fanconi anemia
is a risk factor for developing acute myeloid leukemia.
Whether non-ionizing radiation
causes leukemia has been studied for several decades. The International
Agency for Research on Cancer expert working group undertook a detailed
review of all data on static and extremely low frequency electromagnetic
energy, which occurs naturally and in association with the generation,
transmission, and use of electrical power. They concluded that there is
limited evidence that high levels of ELF magnetic (but not electric)
fields might cause childhood leukemia. Exposure to significant ELF
magnetic fields might result in twofold excess risk for leukemia for
children exposed to these high levels of magnetic fields. However, the
report also says that methodological weaknesses and biases in these
studies have likely caused the risk to be overstated. No evidence for a
relationship to leukemia or another form of malignancy in adults has
been demonstrated. Since exposure to such levels of ELFs is relatively
uncommon, the World Health Organization concludes that ELF exposure, if
later proven to be causative, would account for just 100 to 2400 cases
worldwide each year, representing 0.2 to 4.9% of the total incidence of
childhood leukemia for that year (about 0.03 to 0.9% of all leukemias).
Diagnosis is usually based on
repeated complete blood counts and a bone marrow examination following
observations of the symptoms, however, in rare cases blood tests may not
show if a patient has leukemia, usually this is because the leukemia is
in the early stages or has entered remission. A lymph node biopsy can
be performed as well in order to diagnose certain types of leukemia in
certain situations.
Following diagnosis, blood
chemistry tests can be used to determine the degree of liver and kidney
damage or the effects of chemotherapy on the patient. When concerns
arise about visible damage due to leukemia, doctors may use an X-ray,
MRI, or ultrasound. These can potentially view leukemia's effects on
such body parts as bones (X-ray), the brain (MRI), or the kidneys,
spleen, and liver (ultrasound). Finally, CT scans are rarely used to
check lymph nodes in the chest.
Despite the use of these methods
to diagnose whether or not a patient has leukemia, many people have not
been diagnosed because many of the symptoms are vague, unspecific, and
can refer to other diseases. For this reason, the American Cancer
Society predicts that at least one-fifth of the people with leukemia
have not yet been diagnosed.
Mutation in SPRED1 gene has been
associated with a predisposition to childhood leukemia. SPRED1 gene
mutations can be diagnosed with genetic sequencing.
Leukemia was first observed by
pathologists Rudolf Virchow and John Hughes Bennett in 1845. Observing
an abnormally large number of white blood cells in a blood sample from a
patient, Virchow called the condition Leukämie in German, which he
formed from the two Greek words leukos, meaning "white", and aima,
meaning "blood". Around ten years after Virchow and Bennett's findings,
pathologist Franz Ernst Christian Neumann found that one deceased
leukemia patient's bone marrow was colored "dirty green-yellow" as
opposed to the normal red. This finding allowed Neumann to conclude that
a bone marrow problem was responsible for the abnormal blood of
leukemia patients.
By 1900 leukemia was viewed as a
family of diseases as opposed to a single disease. By 1947 Boston
pathologist Sydney Farber believed from past experiments that
aminopterin, a folic acid mimic, could potentially cure leukemia in
children. The majority of the children with ALL who were tested showed
signs of improvement in their bone marrow, but none of them actually
were cured. This, however, led to further experiments.
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