Leukemia is a type of blood cancer closely related to non-Hodgkin lymphoma, myeloma, and myeloproliferative neoplasms (MPNs). Leukemia begins when blood stem cells in the bone marrow develop genetic mutations that cause leukocytes (white blood cells) to develop abnormally, grow too quickly, and avoid destruction by the immune system. Overproduced cancer cells multiply in the bone marrow and crowd out healthy blood cells, leading to symptoms of leukemia.
There are four main types and many subtypes of leukemia. Each type of leukemia can have different symptoms and a different prognosis, depending on multiple factors. Doctors pinpoint a specific type of leukemia during the diagnosis process. Knowing the subtype and specific characteristics of an individual’s leukemia allows a doctor to determine which treatment options are likely to be most effective.
It is impossible to cover every type of leukemia here. This article will discuss how leukemia is categorized and discuss the four main types of leukemia and some common subtypes.
Read on to learn more about how leukemia is categorized, or go straight to one of the four main types of leukemia:
Each case of leukemia is either acute or chronic.
In the bone marrow, all blood cells start out as hematopoietic (blood-forming) stem cells, capable of developing into any type of blood cell. Stem cells then divide into one of two progenitor cells — myeloid or lymphoid. Progenitor cells can be thought of as the two main branches of the blood cell family.
Myeloid progenitor cells develop further into:
Lymphoid progenitor cells develop further into a specific type of white blood cell known as a lymphocyte. Lymphocytes include:
Each type of blood cell undergoes several stages of development before becoming a mature, functional cell. After establishing which lineage of white blood cells (lymphoid or myeloid) a case of leukemia involves, the condition is further subtyped by the maturation stage of the abnormal cells.
Cytogenetic testing, which involves examining the chromosomes of cancer cells for specific mutations, is often part of the process of diagnosing leukemia. Some genetic mutations can confirm diagnosis, while others can help predict which leukemia treatments are likely to be most effective or indicate how rapidly the disease is likely to progress.
Many different genetic mutations are associated with different subtypes of leukemia. For example, chromosomes 9 and 22 sometimes swap sections during cell division, resulting in a mutation. The mutated chromosome 22 is known as the Philadelphia chromosome, and the resulting gene is referred to as BCR-ABL. This gene can be present in many types of leukemia, including chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL). For this reason, CML and ALL may be subtyped as Philadelphia-positive (Ph+) or Philadelphia-negative (Ph-). Doctors may recommend different treatments based on whether a case of CML or ALL is Ph+ or Ph-.
The same situation applies to many other genetic mutations specific to different types of leukemia. Read more about genetic mutations and causes of leukemia.
Most cases of leukemia fall under four main categories: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and chronic myeloid leukemia (CML). Many of these also have several subtypes. Some types of leukemia are further classified by stage or phase.
ALL is an acute form of leukemia that involves lymphocytic cells in earlier stages of development. ALL is the most common type of leukemia in children and young adults under 25. The risk for developing ALL is highest in children under the age of 5. The risk for ALL decreases through the 20s, then rises after age 50. However, it is rare for adults to develop ALL. ALL may also be referred to as acute lymphocytic leukemia and acute lymphoid leukemia.
Previously, doctors used the French-American-British (FAB) classification of ALL to describe the appearance of leukemia cells under the microscope. Today, most doctors use the World Health Organization (WHO) system to classify types of ALL based on genetic changes. Using the WHO system, the two main subtypes of ALL are defined by which type of lymphocyte they involve, either B cells or T cells.
B-cell ALL, the most common subtype, develops from immature lymphocytes that would normally become B cells. B-cell ALL accounts for 88 percent of cases of ALL in children and 75 percent of cases of ALL in adults. Most cases of B-cell ALL involve immature B cells, and are known as precursor or pre-B-cell ALL. Mature B-cell ALL is also referred to as Burkitt type ALL.
B-cell ALL may be further subdivided by the specific genetic abnormalities of the cancer cells. There are many subtypes of B-cell ALL based on genetic mutations. Some examples include:
T-cell ALL develops from immature lymphocytes that would normally become T cells. T-cell ALL occurs more often in adults, making up 25 percent of cases of ALL in adults and 12 percent of cases in children. T-cell ALL is more likely to develop in men than in women.
Either B-cell or T-cell lymphoblastic leukemias may be subtyped as being Philadelphia-positive (Ph+) or Philadelphia-negative (Ph-).
The prognosis for ALL depends on many factors, including age, the genetic characteristics of the cancer cells, and the initial response to treatment. Younger people tend to have a better prognosis than older people with ALL. ALL can spread from the bone marrow to the liver, lymph nodes, brain, and testes.
People who achieve complete remission — showing no sign of minimal residual disease (MRD) after four to five weeks of starting treatment — tend to have a better prognosis than those whose ALL does not respond completely. After ALL has been treated, it may be described as being in remission or as active disease, depending on how the cancer responded to treatment.
AML is an acute form of leukemia that involves myeloid cells in earlier stages of development. AML is the most common type of acute leukemia, the most common type of leukemia in people between the ages of 25 and 49, and one of the most common types in those ages 50 to 64. AML can also occur in children. AML is also referred to as acute myelogenous leukemia, acute myelocytic leukemia, acute granulocytic leukemia, and acute nonlymphocytic leukemia.
AML may be classified using two different systems. The French-American-British (FAB) classification of AML was developed in the 1970s. Subtypes M0 through M7 are based on the type of white blood cell involved and the stage of maturity of the cells.
The World Health Organization (WHO) system for classifying AML was updated in 2016 to focus on specific genetic abnormalities, underlying causes, and other characteristics that affect prognosis.
AML progresses rapidly without treatment. AML is a fast-moving type of leukemia that can spread to other sites including the lymph nodes, liver, spleen, testicles, and central nervous system (CNS), which comprises the brain and spinal cord. The prognosis for AML depends on many factors, including a person’s age and medical history, the subtype of AML, and whether cancer has spread to the CNS.
AML is not classified in stages like some types of cancer. Instead, it is described as being untreated, or in remission (no longer progressing after successful treatment), or recurrent (progressing again after a period of remission). Treatment options for AML depend on many factors. Read about treatments for AML.
CLL involves lymphocytes — mostly B cells, but sometimes T cells. CLL is so closely related to small lymphocytic lymphoma (SLL), a form of non-Hodgkin lymphoma, that they are considered different expressions of the same disease. In other words, CLL/SLL is both a type of leukemia and a type of lymphoma. In CLL, cancer cells are mainly concentrated in the bone marrow and blood, and in SLL, cancer cells are concentrated in the lymph nodes and other lymphoid tissues.
Although CLL is considered a chronic form of blood cancer, in some cases it can progress rapidly. CLL/SLL is common in older adults and is the most common type of leukemia in people aged 65 and over. The risk for developing CLL/SLL increases with age. CLL/SLL is more than twice as common in men than in women.
Monoclonal B-lymphocytosis (MBL) is a condition in which someone has CLL-like cells that may or may not develop into CLL. Between 1 percent and 2 percent of those with MBL develop CLL each year.
CLL/SLL can be categorized based on how fast it is growing, which type of lymphocyte is involved, and the stage of the cancer.
CLL/SLL can be described as indolent (slow-growing) or aggressive (faster-growing). Indolent CLL may not require immediate treatment in some cases. However, indolent cases of CLL/SLL can transform into a more aggressive form. It’s important to treat aggressive CLL early.
CLL/SLL can be classified by which type of lymphocyte is involved. B-cell CLL/SLL accounts for more than 95 percent of cases of CLL/SLL. T-cell prolymphocytic leukemia is found in 1 percent of people with CLL/SLL.
Unlike most other forms of leukemia, CLL/SLL stages reflect the spread of the disease in the body. There are two classification systems for CLL/SLL stages, the Rai Staging System and the Binet Classification System.
The prognosis for CLL/SLL varies based on many factors, including age, whether the cancer is indolent or aggressive, how widespread cancer cells are in the bone marrow, and the specific genetic characteristics of the cancer cells. Some genetic mutations are associated with a better prognosis, while others are associated with a worse prognosis.
CML is generally a chronic form of leukemia, but it can transform into a more aggressive form that becomes harder to treat. CML develops in myeloid cells. CML may also be referred to as chronic myelogenous leukemia, chronic granulocytic leukemia, and chronic myelocytic leukemia. CML is also considered to be a type of myeloproliferative neoplasm (MPN), a rare category of blood cancer closely related to leukemia.
CML accounts for about 15 percent of leukemia cases in adults, with nearly half of cases diagnosed in people aged 65 or older. CML is rare in children. CML is slightly more prevalent in men than in women.
CML may be subtyped as being Philadelphia-positive (Ph+) or Philadelphia-negative (Ph-). Most cases of CML are Ph+.
CML has three phases. Symptoms and treatment options vary, depending on the phase. Phases are distinguished by the ratio of cancer cells to healthy cells present in the bone marrow and blood.
The three phases of CML are:
About 90 percent of people are in the chronic phase when they are diagnosed with CML. The chronic phase of CML may last for years, but without treatment, CML will eventually progress to the accelerated phase and then the blastic phase within three or four years. When symptoms such as fatigue, fever, and splenomegaly (enlarged spleen) occur during the blastic phase, the situation is known as a blast crisis. CML that relapses after treatment or fails to respond to treatment is called resistant CML.
The prognosis for a case of CML varies based on many factors, including a person’s age and general health, the number of cancer cells present, the phase of CML, and whether the spleen was enlarged at the time of diagnosis.
Some types of leukemia are more difficult to classify. Undifferentiated and biphenotypic acute leukemias, also called mixed lineage or mixed phenotype acute leukemias (MPALs), may show characteristics of more than one type of leukemia. Others may have traits in common with leukemia and another type of blood cancer, such as lymphoma or myelodysplastic syndromes (MDS).
These subtypes may have a poorer prognosis than other types of leukemia. There is no agreed-upon treatment strategy among doctors and researchers.
Several rarer forms of leukemia are considered to be related to CLL, but with some differences. These include prolymphocytic leukemia, large granular lymphocyte leukemia, and hairy cell leukemia.
Read about treatment options for different types of leukemia.
Leukemia Condition Guide
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