What Leukemia Is
Leukemia is a malignant disease of the blood-forming cells. It involves white blood cells
that do not mature and that reproduce too rapidly. Eventually, they replace the normal
bone marrow, leaving insufficient room for the "good" cells. Such cells include red blood
cells, nonmalignant white cells, and platelets, all of which are vital for the body to
function properly. The leukemic white cells take over the bone marrow and make it
impossible for normal cells to grow and mature to function as they should. Leukemic
cells look different from healthy cells under the microscope and are unable to do their
The information in this fact sheet comes from Henderson, Lister, and Greaves' Leukemia,
sixth edition; from the National Cancer Institute's Report on Leukemia; and from the
tenth edition of Wintrobe's Clinical Hematology.
Blood is composed of two parts: the plasma, a straw-colored, clear fluid, and the blood
cells, also known as corpuscles, carried by the plasma. There are three different kinds of
corpuscles in blood: the red cells (erythrocytes), the white cells (leukocytes), and the
platelets (thrombocytes). White cells have nuclei, but red cells don't.
Blood cells are formed in the bone marrow (the spongy tissue inside the bones) from
precursor cells called stem cells. These stem cells produce several types of blood cells:
red blood cells, some varieties of white blood cells (WBC), and platelets. Each stem cell
can reproduce (clone) itself and give birth to a number of immature cells (blasts) and
committed precursor cells.
Normal bone marrow is composed of many different clones all reproducing themselves
and forming new cells that will, in turn, develop into red blood cells, white blood cells,
and platelets. The normal marrow also balances the production of these different cell
types so they appear in the blood in their proper proportions. Some blood cells develop in
the spleen and lymph nodes as well. Blood circulates in the marrow and throughout the
Red blood cells
Erythrocytes, or red blood cells (RBC), make up the largest proportion of blood cells in
the body. Constituting approximately 45 percent of blood volume, they contain
hemoglobin, an iron-rich protein. The RBC's function is to bind oxygen from the air in
the lungs, carry it to cells throughout the body, and exchange it for carbon dioxide, which
is then eliminated from the lungs through exhalation.
White blood cells
Leukocytes (lymphocytes), or white blood cells (WBCs), are fewer in number than red
blood cells. White blood cells are part of the body's immune system. White cells
constantly scan the body for disease-causing cells, such as bacteria, fungi, or viruses.
Different types of white cells have different roles, for instance in fighting particular types
of invaders. When there is an invasion of disease-causing cells, extra white cells are
produced to battle the infection. Once the white blood cells have done their jobs, the
white cell levels return to normal.
Types of white cells include monocytes, lymphocytes, and granulocytes. Each has a
- Monocytes, the largest white blood cells, literally engulf and destroy invading
bacteria and fungi. They clean up the debris left after other white cells have
successfully overcome other invaders, and they clean up dying cells as well. When
they enter tissues or organs, they are larger in size and are called macrophages: these
cells continue to destroy invading cells.
- Lymphocytes, the smallest of the white cells, are essential to the immune system.
They fight viral infections and assist in the destruction of parasites, fungi, and
bacteria. Each cell has markers on its surface that tell whether it is a natural killer cell
(NK), a T cell (thymus-derived cell), or a B cell (bone-marrow-derived cell) and, if a
B cell, what antibodies it expresses.
Antibodies are proteins produced in response to the presence of foreign substances,
known as antigens. B cells manufacture antibodies, or immunoglobulins, that attach
to foreign substances and make it easier for them to be destroyed. T cells, the second
group, are the body's main defense against viruses, producing substances that help
regulate the immune response. T cells also help the B cells produce antibodies, and
they control the activities of various other white blood cells. New lymphocytes grow
continually in the bone marrow and the lymph nodes, and many clusters of
lymphocytes grow in the spleen.
- Granulocytes, the first defense against many types of infection, take up bacteria and
destroy them with potent chemicals. Granulocytes are divided into several categories:
- Neutrophils are the infection-fighter cells. They carry granules of bacteria-killing
enzymes. Bacterial infections are likely to develop when the neutrophil count is very low.
- Basophils are the rarest and least understood of the white cells. They play an
important role in allergic reactions, such as asthma, hives, and drug reactions.
- Eosinophils defend the body against parasites and also play an important role in
allergic reactions, particularly in conditions known as delayed hypersensitivity reactions.
Platelets, or thrombocytes, are the smallest elements in the bloodstream. Platelets are
essential to control bleeding. They are the cells that allow your blood to clot, and they
stop the bleeding if you are cut. When platelets are low, minute red or purple dots may
appear in the skin or mucous membranes. These dots, called petechiae, are caused by the
escape of small drops of blood. They are a warning that platelet numbers may be
abnormally and seriously low.
A blast is an immature cell derived from a stem cell. In bone marrow, lymphoid organs,
or blood, it may be a monocyte (monoblast), lymphocyte (lymphoblast), myelocyte
(myeloblast), erythrocyte (erythroblast), or the platelet parent megakaryocyte
(megakaryoblast). Blasts generally constitute less than 5 percent of the cells seen in the
bone marrow and should never be seen in the peripheral blood. Normal blast cells divide
over and over again, and it is their growth that fills the marrow with the diverse types of
immature and developing blood cells that are seen in a normal bone marrow specimen.
Normal blasts develop into functioning cells. Leukemia blasts remain in a semi-mature
state, multiply excessively, and may be present in large numbers in the bloodstream.
These leukemic blasts do not provide defenses against infection.
Plasma cells (committed B cells) make five different types of immunoglobulins (Ig) or
antibodies (Ab). They are IgA, IgD, IgE, IgG, and IgM. More is known about some of
these than others.
Little to nothing is known about IgD. IgE seems to be increased in allergic reactions. IgA
is found in body secretions (tears, blood, intestinal fluid, saliva, and such). Apparently it
is used as protection against antigens coming into the body from the gastrointestinal tract
and other mucous membranes. IgM is the first antibody made in response to an antigen
attack and is the first antibody to be made by the fetus. While it can be made fast, it is
quite primitive and doesn't work all that well.
IgG is the best known of the immunoglobulin classes. It is highly reactive, increasing the
activity and specificity of the granulocytes and monocytes and able to move into
interstitial fluids and other places with ease. It neutralizes bacterial toxins and initiates
complement activity, which in turn further increases the action of granulocytes and
monocytes. Complement can also break down certain antigens all by itself.
When you are deficient in IgG, everything about your immune system works a little
slower and less effectively. When you have enough IgG, simple everyday things (say, the
bacteria that enter the blood stream during normal tooth brushing) are eliminated within
minutes, and you don't notice it. But when there is less or less-effective IgG, then there is
more stress on the system, and it takes longer for the same elimination to occur.
Something that you might have shrugged off becomes noticeable, and something that
might have been noticeable becomes important.
IV IgG is a collection of plasma taken from donors. It should contain a high amount of
effective IgG and, as a consequence of having that, your overall efficiency in handling
antigens is increased.
How leukemia begins
Leukemia is a disease of the white blood cells. Each kind of leukemia involves a
particular white blood cell and reflects the level of maturation of the cell. The blood cell
involved mutates to become a cancer cell. This process of mutation is believed to be
multistepped, occurring at several different times in the cell's maturation process.
In leukemia, white cells in the bone marrow and/or lymphoid tissues begin to reproduce
uncontrollably. The rapidly multiplying cells start out in the bone marrow, crowding out
the useful cells. After a while they spill over into the blood stream and may be found in
vital organs of the body. The most commonly affected organs are lymph nodes, the
spleen, liver, and skin. Sometimes the kidneys, brain, or other parts of the nervous system
are involved. Ultimately all tissue and organs are susceptible to leukemic infiltration.
How leukemia is diagnosed
Leukemia diagnoses may come like a bolt out of the blue. Sometimes painful or annoying
symptoms appear, so a trip to the doctor becomes a necessity. Often, fatigue or repeated
infections finally push you to visit the doctor. The initial diagnosis of leukemia usually is
made through evaluation of the blood work. In some leukemias, the diagnosis is an
accidental finding when a blood test is ordered for some other reason.
Early signs of the leukemias are similar, so laboratory analysis of blood samples is
required to determine which particular leukemia is present. Fortunately, today
sophisticated tests are available to help doctors discover cell patterns that indicate
specific leukemic types, but sometimes the pathologists still may be unable to type a
particular patient's leukemia definitively at first.
Diagnosing leukemia can be difficult and confusing. Often, the doctor will want to do
sophisticated blood tests to discover which kind of chromosome or genetic pattern is
present. Other tests, like biopsies (samples of tissue from the affected organ) may be
needed. A bone marrow aspiration and biopsy (BMB) may be used to verify blood test
results. Whatever the reasons, diagnosis will be based on blood test results, the patient's
description of symptoms, pathology reports, and the doctor's findings after physical
examinations. Family history and reports of occupational and environmental exposures
may also be considered. Often, additional information is obtained from x-ray
examinations and body scans. Staging and risk levels will be determined at this time and
serve as the basis for subsequent treatment decisions.
In some cases a patient is diagnosed with one form of leukemia, and later his doctor
discovers that it is really another form entirely. Acute lymphocytic leukemia may be
confused with acute myelogenous leukemia, hairy cell leukemia, or non-Hodgkin's
lymphoma. The symptoms of lymphomas and leukemias often overlap in their initial
presentations. Hairy cell leukemia and mantle cell lymphomas are also often
misdiagnosed as chronic lymphocytic leukemia.
Kinds of adult leukemia
There are many kinds of leukemias. Although there are different leukemia diagnoses,
there are many similarities among the types. They all are characterized by excessive
production of non-functioning white blood cells, present with similar symptoms, can
show genetic and chromosomal abnormalities, and may share similar environmental
exposure. These similarities are part of the reason that difficulties are sometimes
encountered in making a diagnosis.
Differences among types of leukemia become clear when the blood work is evaluated.
Genetic differences are seen in the cells. Chromosome patterns are not the same. Specific
cancer cells are identified by their chemical composition or by unique arrangements of
constituents on the cell surfaces and are found in certain patterns.
In order to distinguish among the types, leukemias are subdivided into acute or chronic
forms. The determination as to whether a type of leukemia is chronic or acute is based
upon the level of maturation of the cells involved. The sections that follow describe the
various types of leukemias.
In acute leukemia, the majority of cells are non-functioning blasts. The number of blasts
increases rapidly, crowding out the working cells, and the disease gets worse quickly.
Treatment is needed at once or the disease is likely to be fatal.
Two major kinds of acute leukemias have been identified, both presenting with identical
symptoms. The type of white cell involved determines the diagnosis of which kind of
acute leukemia is made. One is lymphocytic leukemia, affecting the lymphocytes, and the
other is myelogenous leukemia, involving the granulocytes.
Acute lymphocytic leukemia (ALL)
This is the most common form of childhood leukemia (75 to 80 percent of all childhood
leukemias). Only 20 percent of all adult leukemias are classified as ALL. The number of
individuals diagnosed increases significantly after age 50. ALL is characterized by
extreme proliferation of lymphocyte cells in the bone marrow and in the lymphatic
system. B cells or T cells may be involved.
Acute myelogenous leukemia (AML)
This disease occurs in both adults and children, but it is far less common in young people.
It is also called acute nonlymphocytic leukemia because lymphocytes are not affected.
The cells involved in AML are the myeloblasts that proliferate uncontrollably and
prevent other needed cells from doing their jobs. AML affects about 1.5 percent of people
In chronic leukemia, some blasts are present, but often these cells have matured further
and can carry out some of their duties for a longer period of time. These cells increase
gradually, so this cell development pattern is called "chronic." Treatment of chronic
leukemias may be delayed until physical symptoms and blood work indicate it is needed.
Chronic myelogenous leukemia (CML)
CML accounts for 15 percent of the adult leukemias. It is one of the chronic leukemias
that eventually moves into an acute phase, becoming AML 70 percent of the time and
ALL in 30 percent. Some 90 percent of patients with CML show a unique chromosome
abnormality known as the Philadelphia chromosome (Ph).
CML is also called chronic myeloid or chronic myelocytic leukemia. It is also known as
chronic granulocytic leukemia (CGL). CML is a form of leukemia that affects the cells
that make granulocytes and platelets. In its early stages it produces an increase in the
numbers of granulocytes and platelets, but these cells still function normally and the
patient may have no symptoms. This situation may continue for three or four years
(known as chronic phase). Eventually the nature of the disease changes, and CML starts
to behave like other leukemias.
Chronic lymphocytic leukemia (CLL)
This has been the most common adult leukemia, comprising 25 to 30 percent of all adult
leukemias. It affects 17 percent of people with leukemia. CLL has been considered a
disease of elderly men, with a 2:1 ratio of men to women. Now, increasing numbers of
younger people are also being diagnosed with CLL, possibly because routine blood
exams are more common and may be facilitating earlier detection. In past years,
treatment and research options were not undertaken because it was believed that if you
had CLL you would die of something else before you needed treatment. Today there is a
great deal of research being done, providing more promising treatment options.
CLL is a disease in which the affected lymphocytes divide slowly but in a poorly
regulated manner. They live much longer than usual and over time are unable to perform
their proper functions.
CLL is divided into subsets depending upon whether T lymphocytes or B lymphocytes
are involved. T-CLL is also known as large granular-cell lymphocytosis. It is associated
with exposure to HTLV-1 (human T cell lymphotropic retrovirus). This should not be
confused with HTLV-3 (also known as HIV-1), the virus responsible for acquired
immunodeficiency syndrome (AIDS). In 1977, a new leukemia classification was created
called adult T-cell leukemia (ATL).
The subclassification of CLL is as follows:
- B-CLL (more than 95 percent of all CLL cases) has also been described as small
lymphocytic lymphoma, and often a pathology report will say CLL/SLL when providing
a diagnosis because the same cell is affected in both diseases. In one instance, it behaves
like a leukemia with a high white blood count and, in the other, it behaves like a small
lymphocytic lymphoma, with tumorous lumps in the lymph nodes.
- CLL/PL: a mixture of CLL cells and prolymphocytes are present in the blood sample.
Ten to 55 percent of the cells are prolymphocytes (see below).
- CLL/Mixed: variations in cell sizes are seen with some cells larger than CLL
lymphocytes. Some have irregular nuclei that appear to have clefts in them.
Other chronic lymphocytic leukemias
Many variants of lymphoid neoplasms are known and recognized. They differ from true
CLL in the picture they present under the microscope and in the surface markers of
specific cells that are proliferating. In hairy cell and splenic lymphoma, the cells have
finger-like projections, like a veil, that look hairy under the microscope. Prolymphocytic
leukemia, on the other hand, is believed to arise from cells called prolymphocytes.
- Hairy cell leukemia (HCL). Hairy cell leukemia accounts for only 2 percent of adult
leukemias. The cells involved in HCL are lymphocytes with filamentous (hairy)
projections from the cell surface. It is a rare chronic leukemia. HCL may involve B
cells or T cells, but the latter is extremely uncommon. In about one-half of HCL
patients, the marrow is scarred, so it is difficult to do a simple bone marrow
aspiration, and a core biopsy may be required for diagnosis.
- Splenic lymphoma with villous lymphocytes (SLVL). This variant of CLL is associated
with hairy cell leukemia, above. Both HCL and SLVL always show spleen
involvement. Villous lymphocytes have small protrusions--like veils or filaments
extending from the cell membrane--that are wider and more billowy than those seen
in HCL. SLVL is also often confused with CLL, but the cell markers are more
consistent with non-Hodgkin's lymphoma than CLL.
- Prolymphocytic leukemia (PLL). PLL presents as a proliferation of cells called
prolymphocytes. To sustain a diagnosis of PLL there must be more than 55 percent
prolymphocytes. The spleen is involved but not the lymph nodes. PLL may affect
either B cells (B-PLL) or T cells (T-PLL). The latter accounts for 20 percent of all
cases of PLL. Sometimes both lymphocytes and prolymphocytes are involved. Then
the disease is described as CLL/PLL.
- Adult T cell leukemia (ATL). Established as a distinct clinical entity in 1977 in Kyoto,
Japan, this leukemia appears later in life, with frequent rashes, skin involvement, and
lymph node and spleen enlargement. Sometimes the peripheral white cell count is
elevated with abnormal lymphoid cells, but often there is only anemia, low platelets,
and bone marrow infiltration. Patients show human T cell lymphotropic virus type-1
(HTLV-1) as a causative agent. Exposure to the virus appears to occur in childhood.
The disease then seems to manifest itself after a long period of dormancy. The largest
number of cases has been seen in southwestern Japan. There are four subtypes: acute
or prototypic ATL in which patients are often resistant to chemotherapy; lymphoma-type ATL, which presents with prominent lymph node involvement but few ATL
cells; chronic ATL (which used to be classified as T cell CLL), in which the WBC is
elevated and skin lesions are present; and smoldering ATL, in which there may be 5
percent or more abnormal lymphocytes of the T cell type in the peripheral blood for
many years and may present with skin or lung lesions.
This fact sheet was adapted from Adult Leukemia (forthcoming), by Barbara B. Lackritz © 2001 by Patient-Centered Guides. The content on which this fact sheet is based has been reviewed by several MDs and will receive further technical review prior to publication. For more information, call (800) 998-9938 or check www.patientcenters.com for publication announcement.