Blood consists of three types of cells and cell fragments floating in a liquid called plasma. These cellular components are:
- Red Blood Cells ("erythrocytes," "RBCs") - oxygen-carrying cells
- White Blood Cells ("leukocytes," "WBCs") - cells that help make up the body's immune system
- Platelets ("thrombocytes") - fragments of cells that play an important role in formation of blood clots
The total number of white blood cells normally ranges from 4 million to 11 million cells per milliliter of blood.1One teaspoon is made up of about five milliliters. Leukemias are a group of diseases characterized by increased numbers of white cells in the blood and bone marrow.2
In 2023, the American Cancer Society estimates that 59,610 new leukemiaA cancer affecting the cells that develop into white or red blood cells. Both of these cell types originate from stem cells in bone marrow. Red blood cells function to carry oxygen to our tissues and the white cells (leukocytes) are part of our immune system. The cancerous cells often accumulate in the blood. cases will be diagnosed and 23,710 people will die from the disease in the United States.3
View a leukemia survivor's perspective: Interview with Tony LaRocco
Please visit the following sections to learn more about leukemia:
- White Blood Cells
- Types of Leukemia
- Risk Factors
- Symptoms
- Detection and Diagnosis
- Leukemia Tumor Biology
- Treatment
- Leukemia Resources
- Section Summary
Learn more about leukemia or make an appointment at the Winship Cancer Institute of Emory University.
The cells found in blood begin their lives in the middle part (marrow) of some bones. Bone marrow is the source of all blood cells in adults. When cancer arises from one of these cells, the blood no longer has the correct balance of cell types. This can lead to many of the symptoms seen with blood cell cancers. More detailed information is below.
There are five types of leukocytes (white blood cells) found in the blood:
- Basophils
- Eosinophils
- Lymphocytes
- Monocytes
- Neutrophils
Each cell type has a specific role to play in our body's immune system. Important overall functions of the immune system include:
- defense against certain invaders
- removal of dead or damaged cells
- destruction of cancer cells.
Learn more about the immune system
Blood cell formation begins with a special cell located in the bone marrow called a hematopoietic stem cellCells capable of developing into more than one cell type. All of the cells in a human body come from the division and subsequent differentiation of a single cell, formed from the fusion of an egg and sperm. This original cell has the capability to form any cell type and is called totipotent. As tissues develop the cells lose the ability to form all other tissues, and become 'committed' to forming only one or a few cell types. These stem cells are called pluripotent. An example are bone marrow cells that form many different kinds of blood cells. Stem cell replacement allows for the pluripotent stem cells in bone marrow to be replaced after high doses of chemotherapy. Many fully differentiated cells are not capable of cell division and are replaced when they die by the division of stem cells in that tissue. Many forms of cancer are thought to be the result of abnormal division of stem cells.. Unlike most cells, the hematopoietic stem cell (and stem cells in general) has the capability for self-renewal as well as the ability to give rise to any one of the separate blood cell types. This means that as the stem cell divides in two, one cell replaces the original stem cell and the other begins the multi-step process of developing into a mature blood cell.
It is important to note that hematopoietic stem cells are different from embryonic stem cells. While hematopoietic stem cells can develop into any type of blood cell, embryonic stem cells can develop into any cell type in the entire body.
Blood cell precursors usually progress through a series of stages in the bone marrow before entering the circulating blood stream. Signals from surrounding cells in the bone marrow can help stimulate stem cells to divide as well as develop and mature into specific blood cell types. Normal cell division is also regulated by an important process known as the cell cycle. Disruption of this process is central to the development of leukemia.4Learn more about the cell cycle
In the same way that family trees may be divided into bloodlines, the five types of leukocytes (white blood cells) are divided into two groups (lineages), based on how they are developed. The myeloid cells include monocytes, neutrophils, eosinophils and basophils. The lymphoid cells include B lymphocytes, T lymphocytes, and Natural Killer (NK) cells. Learn more about lymphocytes
Leukemias are classified into 4 main categories, based on the type of white blood cell affected (lymphoid vs. myeloid) and characteristics of the disease (acute vs. chronic):
- Acute Lymphoblastic Leukemia
- Acute Myeloid Leukemia (Acute Myelogenous Leukemia)
- Chronic Lymphoid Leukemia (Chronic Lymphocytic Leukemia)
- Chronic Myeloid Leukemia (Chronic Myelogenous Leukemia)
Acute leukemias are generally aggressive diseases in which cancerous transformationThe process by which a normal cell is converted to a cell that has the characteristics of cancer cells. The event causing the change can be an alteration in an oncogene or infection with an oncogenic virus. Transformed cells demonstrate several characteristic differences from normal cells including: density independent growth, anchorage independent growth, lack of dependence on growth factors. occurs at early stages in the development of the affected blood cell. If untreated, these diseases can be rapidly fatal.2
Chronic leukemias are characterized by a slower progression than acute leukemias. These leukemias are more difficult to cure, so the approach to therapy is often conservative and aimed at controlling symptoms.5
Acute Leukemia
Acute leukemias are caused by damage to stem cells or cells in the early stages of development in the bone marrow. Mutations affecting control of cell division, differentiationThe maturation of a stem cell into a fully functional cell. Fully differentiated cells are often not able to divide and many cancers are thought to arise via mutations in the small number of stem cells that remain in the tissue., and cell death lead to the accumulation of early blood cell precursors known as blast cells.2
Below is a short animation about acute leukemia.
Acute Lymphoblastic Leukemia (ALL)
ALL is the most common form of leukemia diagnosed in children.6 The incidence of ALL peaks between the ages of 3-7, falls by 10 years of age, and rises again after the age of 40.7
Acute Myeloid Leukemia (AML)
AML represents 10-15% of leukemias diagnosed in childhood and is the most common type of acute leukemia diagnosed in adults.8
Chronic lymphoid leukemias are diseases characterized by the accumulation of fully developed B or T lymphocytes in the blood. These diseases are closely related to lymphomas, in which lymphocytes accumulate in lymph nodesA grape-like cluster of lymphatic tissue. Lymph nodes (or lymph glands) filter the lymph fluid that flows through the lymphatic system. Lymph nodes collect fluid from discrete regions of the body and are often examined for the presence of metastasizing cancer cells. and vessels.9
Chronic Lymphocytic Leukemia (CLL)
By far the most common type of chronic lymphoid leukemia involves B lymphocytes. CLL mainly affects elderly individuals, with a peak incidence between 60 and 80 years of age. 9 It is the most common form of leukemia in Western countries.10 CLL follows a variable course, with survival ranging from months to decades.10
Other types of chronic lymphoid leukemias include:9
- Prolymphocytic leukemia (PLL)
- Hairy cell leukemia (HCL)
- Plasma cell leukemia
- Large granular lymphocytic leukemia
- T-cell prolymphocytic leukemia (T-PLL)
Chronic Myeloid Leukemia (CML)
CML is a disorder of a hematopoietic stem cell. The disease, which accounts for approximately 15% of leukemias, occurs most frequently between the ages of 40 and 60 years. Laboratory tests reveal increased numbers of cells belonging to the myeloid cell line (monocytes, neutrophils, basophils, eosinophils) at various stages of development circulating in the bloodstream.5
Although the cause of leukemia in most patients is unknown, several factors are associated with an increased risk of developing the disease. Factors that influence the risk of developing leukemia include:
- Age
- Prior ChemotherapyTreatment of cancer patients with anticancer drugs. Commonly called 'chemo'. These drugs work by attacking cell growth or division. Often these agents are used in combination to take advantage of their different modes of attack on cell division.
- Ethnicity/Gender
- Inherited syndromes (such as Down Syndrome)
- Ionizing RadiationIn cancer biology: A cancer treatment in which high energy beams are used to kill cancer cells. Radiation can also cause genetic damage that can lead to cancer. As an example, skin cancer is believed to be greatly increased by exposure to ultraviolet (UV) radiation from the sun.
- Infection by certain viruses
- Cigarette smoking
The relative effects of these and other risk factors in any given case of cancer are variable. Some of these and other risk factors are discussed below.
Age
The risk of developing most types of leukemia increases steadily with age. However, the most common age groups for developing acute lymphoblastic leukemia (ALL) are between the ages of 3-7 and also after the age of 40. 11 The reason for this peak in early childhood ALL remains uncertain.
More information about the relationship between cancer and age can be found in the Mutation section.
Chemotherapy
There is a subset of acute myeloid leukemia (AML), known as "secondary AML" or "therapy-related myeloid leukemia," which can develop following treatment with chemotherapy. Although a causal relationship is implied by the name, the exact mechanism remains unknown.12Prognosis for secondary AML is generally unfavorable compared to primary AML.8
Ethnicity/Gender
With the exception of chronic myeloid leukemia (CML), which has a similar incidence in whites and blacks, leukemia occurs more commonly in those of white ancestry compared to those of Asian, Hispanic and black ancestry. Leukemia also occurs more frequently in males than females.11
Inherited Syndromes
Children with Down syndrome (DS) have a roughly 20-fold increased risk of developing childhood leukemia compared to children without DS.13Approximately 10% of children with DS are born with a "transient leukemia" that resolves spontaneously within months of birth. One to two percent, however, develop a malignantA tumor that has invaded neighboring tissue. acute leukemia requiring chemotherapy by the age of 4.14 While several hypotheses have been proposed, the reason for this increased risk remains uncertain.
Other inherited syndromes that increase risk of leukemia include:
Ionizing Radiation
An increase in leukemia has been observed in survivors of the atomic bombing of Japanese cities. Although the risk associated with exposure to lower-level radiation is not clear, studies have shown an increase in leukemia following the use of radiotherapy for ankylosing spondylitis (a form of arthritis) and exposure to diagnostic X-rays of the fetus during pregnancy.18
Viruses
Infection with Human T-cell Lymphotropic VirusThe smallest type of organism known. A single virus particle (called a virion) is much smaller than a cell. Viruses reproduce by invading cells and forcing the cells to make progeny virions. Viruses generally have specific host cells which they infect. Some virus types are associated with specific cancers and can convert normal cells into cancer cells. Examples of viruses associated with cancer are: papillomavirus-cervical cancer, hepatitis virus-liver cancer, Epstein-Barr virus-Burkitt's lymphoma. Virus-induced transformation of cells was one of the very first model systems for the study of cancer. Viruses have also been a key tool in the identification of many oncogenes. Because of their great ability to enter target cells viruses such as adenoviruses are being examined for their ability to deliver genes to cancer cells.-1 (HTLV-I) is linked to the development of Adult T-cell Leukemia/LymphomaA cancer arising in the lymphatic system. The white blood cells affected are part of the body's immune system. The lymphatic system is a large network of vessels that carry fluid and cells of the immune system around the body. Lymph nodes are regional collection centers in the lymphatic system. See also, 'lymphatic system'. (ATLL), a cancer of activated mature T lymphocytes.19Learn more about T lymphocytes
HTLV-I and ATLL are widespread in certain regions of the world, such as the Caribbean basin, Japan, and parts of South America and Africa, while very rare in others.19 Most people who are infected with HTLV-I do not develop leukemia.20 Data from cancer registries in Japan suggest the lifetime risk of developing ATLL among those infected is 2.1% for females and 6.6% for males.21
Although the exact mechanism by which HTLV-I infection induces cancer is not known, laboratory studies have identified several mechanisms which may be involved. 21Learn more about viruses and cancer
Leukemia results in the accumulation of cancer cells in the bone marrow and blood. The presence of large numbers of abnormal cells in the bone marrow can inhibit the marrow from producing normal healthy blood cells. Symptoms caused by bone marrow failure include paleness, tiredness, shortness of breath, excessive bleeding, and increased susceptibility to infections. Cancer cells can also infiltrate organs such as the lymph nodes, spleen, and liver leading to swelling.22
Many patients, however, experience no symptoms at all throughout early stages of the disease.
Watch the full interview with leukemia survivor Tony LaRocco.
The diagnosis of leukemia frequenly occurs following a routine blood test that results in an abnormal blood cell count. 23 Once leukemia is suspected, the doctor may take samples of bone marrow and blood to examine cell morphology (shape). Samples are also sent to the pathology lab to identify proteins located on the surface and chromosomal and molecular changes within abnormal cells. This information is important for diagnosis, determining the prognosis, and tailoring therapy for individual patients.18
Genetic changes that occur in cancer include mutation of key regulatory genes, changes in proteinOne of the four basic types of biomolecule. Proteins are polymers made up of strings of amino acids. Proteins serve many functions in organisms including transport of molecules, structure, cell adhesion and as signaling molecules such as hormones. Many transcription factors, including p53 and Rb are proteins. products, and changes in the amount of product produced by genes (gene expressionThe act of transcription and, if needed, translation of a gene. Regulation of gene expression is tightly regulated. Genes must only be expressed in the correct cells, at the right time and in the correct amount. Abnormal gene expression is always found in cancer cells.). As changes accumulate, cells become more abnormal and cancer progresses. Details of genetic change associated with cancer can be found in the Mutation section.
Advances in leukemia research within recent decades have increased our knowledge about the changes that occur in the disease. A large variety of alterations, including point mutations, amplifications, insertions, deletions, and trisomies are important in development of leukemia. Over 300 chromosomal translocations have been identified so far! A translocation is a rearrangement of parts of a chromosomeA long DNA molecule containing genetic information (genes). Humans have 46 chromosomes. One set of 23 is inherited from each parent. A full set of chromosomes is present in the nucleus of each human cell.. Understanding the changes that occur and their effects on cell function allows doctors to classify leukemia into subsets with distinct prognoses and treatment strategies.10
The example of a common translocation, known as the Philadelphia Chromosome, is discussed below. Learn more about translocations
The Philadelphia Chromosome
Translocations involve chromosome breakage and exchange of chromosome fragments. One such translocation, found in over 95% of chronic myeloid leukemias (CML) as well as some acute lymphoblastic leukemias (ALL), occurs between chromosomes 9 and 22. Part of the proto-oncogeneA gene that normally functions to promote cell division. When these genes are mutated they may produce products that promote cell division in an abnormal fashion. Examples of oncogenes include HER2/neu, ras, and src. See Tumor Suppressors and Oncogenes for more details. abl is removed from chromosome 9 and joined to the bcr gene on chromosome 22. Similarly, part of chromosome 22 is removed and relocated to chromosome 9.24 The exchange leads to the creation of a shortened form of chromosome 22, called the Philadelphia chromosome (after the location of its discovery).
The normal ABL protein functions as a tyrosine kinaseAn enzyme that adds phosphate groups to target molecules. Often the targets of these enzymes are proteins that control the cell division process, so the enzymes play a key role in cell division. See also, kinase.. Tyrosine kinases are enzymes that transfer phosphate groups from ATP to other molecules. Activation of key regulatory enzymes in this manner leads to a cascade of events that ultimately results in cell division. The newly created bcr-abl fusion gene located on the Philadelphia chromosome codes for a protein that has increased tyrosine kinaseAn enzyme that adds phosphate groups to another molecule. Many key proteins controlling gene expression are kinase targets. Addition of a phosphate group to a protein can alter the activity of the protein and are often used as molecular on/off switches. For example, the retinoblastoma tumor suppressor gene is 'off' when phosphate groups are added to the protein at specific locations. Removal of the phosphate groups turns the protein 'on'. Enzymes that remove phosphate groups are known as phosphatases. Note that all enzymes, regardless of function, end in ASE activity, and therefore leads to increased stimulation of cell division, compared to the normal ABL protein. 5
Imatinib (Gleevec®) is a drug that was designed to bind to the BCR-ABL fusion protein. The presence of the drug blocks the binding of ATP, preventing the protein from functioning as a tyrosine kinase. 25 Imatinib (Gleevec®) is the gold standard treatment for chronic myeloid leukemia (CML).10
Learn more about leukemia or make an appointment at the Winship Cancer Institute of Emory University.
As our focus is on the biology of the cancers and their treatments, we do not give detailed treatment guidelines. Instead, we link to organizations in the U.S. that generate the treatment guidelines.
The National Cancer Institute lists the following treatments for leukemia:
- Surgery
- Radiation Therapy
- Chemotherapy
- ImmunotherapyA treatment for a disease (including cancer) that involves the modulation of the immune system. Treatments include the administration of cytokines (proteins produced by cells of the immune system) and vaccinations.
- Stem Cell Transplantation
For more information about how other cancer treatments work, refer to the Cancer Treatments section.
Learn more about Leukemia treatment at the Winship Cancer Institute of Emory University.
Watch interviews with leukemia survivors Tony LaRocco and Julio Farach (in Spanish)
Information about clinical trials:
- General clinical trial information from CancerQuest
- Click here for information about clinical trials from the National Cancer Institute.
- Click here for information about clinical trials from Georgia Clinical Trials Online.
- Click here for information about clinical trials at the Winship Cancer Institute of Emory University
Risks for Leukemia
Leukemia Risk Factors (Mayo Clinic)
Risk Factors for Childhood Leukemia (ACS)
Detection and Diagnosis of Leukemia
Winship Cancer Institute: Leukemia Cancer Diagnosis and Staging Make an Appointment
What You Need to Know About: Leukemia (NCI)
Leukemia Treatments
Adult Acute Lymphoblastic Leukemia Treatment
Adult Acute Myeloid Leukemia Treatment
Chronic Myelogenous Leukemia Treatment
Childhood Acute Lymphoblastic Leukemia Treatment
Childhood Acute Myeloid Leukemia Treatment
Leukemia Survivorship
Leukemia, Lymphoma Society Report
Long Term Risks for Leukemia Survivors
Long Term ffects of Childhood Leukemia Treatment
International Leukemia Resources
Leukemia and Lymphoma Society of Canada
Canadian Cancer Society: Leukemia
Leukaemia Foundation (Australia)
Cancer Council Australia: Leukaemia
Dharamshila Hospital on Leukemia (India)
Introduction
- The cellular component of blood contains red blood cells, white blood cells, and platelets.
- Leukemia is characterized by an increase in the number of white cells in the blood and bone marrow.
White Blood Cells
- There are five types of white blood cells or leukocytes.
- Leukocytes play an important role in our body's immune system.
- All blood cells form from hematopoietic stem cells.
- Blood cell precursors mature in the bone marrow before entering the circulating bloodstream.
- Disruption of the cell maturation process is central to the development of leukemia.
Types of Leukemia
- Leukemia is divided into 4 main categories based on the affected cell type:
- Acute lymphoblastic or myeloid leukemia (ALL and AML)
- Chronic lymphoid or myeloid leukemia (CLL and CML)
- Acute leukemias are generally aggressive whereas chronic disorders exhibit a slower progression.
Risk Factors
- The risk of developing most types of leukemia increases steadily with age.
- Secondary AML can develop following chemotherapy treatment.
- Leukemia occurs more frequently in white males than in any other population.
- Children with Down syndrome (DS) have a roughly 20-fold increased risk of developing childhood leukemia compared to children without DS.
- Exposure to ionizing radiation increases the risk of leukemia.
- The Human T-cell Leukemia Virus Type 1 (HTLV-1) has been linked to the development of Adult T-cell Leukemia/Lymphoma.
Symptoms
- Paleness, tiredness, shortness of breath, excessive bleeding, and increased susceptibility to infections.
- Swelling of the lymph nodes, spleen, and liver.
Detection and Diagnosis
- Blood and bone marrow tests are used to diagnose leukemia.
Tumor Biology
- Many genetic changes occur in cancer. Details can be found in the Mutation section.
Treatment
- Leukemia treatments include: chemotherapy, immunotherapy, radiation therapy, stem cell transplantation and surgery.
Learn more about leukemia or make an appointment at the Winship Cancer Institute of Emory University.