The Different Types of Leukemia
- Acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) are blood cell cancers that start in the bone marrow.
- AML is more common and more aggressive than CML.
- AML is usually treated with high-dose chemotherapy drugs using different regimens.
- CML is typically treated with targeted therapies called Tyrosine Kinase Inhibitors (TKIs), which block the abnormal protein made by the CML cells, eventually killing them.
- Red Blood Cells (RBCs): These cells transport oxygen from the lungs to all areas of the body. Oxygen is carried by a molecule called hemoglobin, which is present inside these cells.
- White Blood Cells (WBCs): These cells form the infection-fighting machinery of the body. They protect the body against bacteria, viruses, and other agents which can inflict serious harm. Without WBCs, the body cannot fight infections.
- Platelets: These are fragments of cells, which play a critical role in forming clots or scabs at the site of injuries. A platelet deficit can make a person especially vulnerable to bleeding after minor injuries.
Due to certain mutations or changes within the DNA of the bone marrow cells, one or more of these cell types can be produced at an abnormally high rate. This can lead to the development of cancers. The most affected cell type is the WBC. Both AML and CML result from an overproduction WBCs.
How are Acute and Chronic Myeloid Leukemias Different?
Read More"AML is a much more aggressive form of leukemia that requires admission to a hospital and high-dose chemotherapy. It is not the same thing as CML. CML is a different disease which just happens to have the word leukemia in its name," says Dr. Eric Winer, Clinal Director for Adult Leukemia at the Dana-Farber Cancer Institute.
CML develops and progresses slowly, which is indicated by the term "chronic" in its name. It has three phases. These are, in order of severity, chronic, accelerated, and blast. More than 90% of CML patients are diagnosed in the least aggressive chronic phase when their chance of recovery with treatment is extremely high. More than 90% of patients with CML are alive five or more years after their initial diagnosis.
RELATED: Understanding Chronic Myeloid Leukemia (CML)
What Causes AML and CML?
Both these leukemias are caused by chance changes and mutations within the DNA.
AML can be caused by changes within the FLT3, RAS, c-KIT, IDH1, IDH2, and various other genes. While these are mutations within different genes, they ultimately have the same effect. They prevent immature myeloblasts from maturing into functional blood cells while simultaneously charging them to grow by leaps and bounds.
CML, on the other hand, occurs due to the formation of the so-called Philadelphia (Ph) chromosome. This chromosome forms when two originally normal chromosomes, 9 and 22 (normal cells have 46 chromosomes in total), break off and fuse together. This fusion brings certain genes together in an unnatural way. In the case of the Ph chromosome, the BCR and ABL1 genes are joined together, forming the abnormal BCR-ABL1 fusion gene. This gene produces a mutant BCR-ABL1 tyrosine kinase, which is a protein (enzyme) that stimulates the CML cells to proliferate in great quantities. These cells are also immature, but they tend to be more mature than the myeloblasts produced by AML.
Who Can Get AML and CML?
Overall, AML is more common than CML, with almost 20,000 cases of AML diagnosed each year in the United States. Comparatively, only 8,000 cases of CML are diagnosed each year in this country.
According to the American Cancer Society, certain risk factors can increase your chance of developing AML and CML. Male gender, older age, and exposure to high doses of radiation can increase a person's risk for either AML or CML.
Some factors increase the risk for AML only, and these include smoking, history of AML within the family, Down syndrome, certain chemotherapy drugs (cisplatin, carboplatin, carmustine. busulfan, melphalan, mechlorethamine, and cyclophosphamide), and exposure to certain hazardous chemicals (benzene, formaldehyde, etc.), among others.
What are the Symptoms of AML and CML?
Many symptoms for both AML and CML overlap. Therefore, symptoms alone may not be the best clue as to whether a patient has one versus the other. Symptoms shared by both leukemias include:
- Fever
- Fatigue/Tiredness
- Weakness
Patients with AML may be more likely to additionally experience:
- Frequent infections
- Easy bruising
- Loss of appetite
- Shortness of breath
- Bone pain
CML patients are commonly asymptomatic. When they do have symptoms, they usually present with:
- Night sweats
- A full feeling on the left side of their stomach, below their ribs
- Unintentional weight loss
How are AML and CML Diagnosed?
An accurate diagnosis of either blood cancer requires a series of tests:
- Peripheral blood smear, which analyzes a blood sample under a microscope to report the numbers and appearance of the different cells present
- Complete blood count (CBC), which reports the number and proportion of different cells within a blood sample
- A bone marrow biopsy, which involves taking a sample of the bone marrow for analysis
- Testing for different proteins present on blood cells (specific proteins are associated with specific cell types)
- Different genetic testing for the different mutations known to cause AML and CML, such as changes in the FLT3, RAS, c-KIT, IDH1, IDH2, and BCR-ABL1 genes
The results of these tests usually guide the final diagnosis. A patient may be diagnosed with AML if they have the following test results:
- Abnormal immature myeloblast cells within the bone marrow in large quantities
- Certain proteins, such as CD13 and CD33, present on blast cell surfaces
- FLT3, RAS, c-KIT, IDH1, or IDH2 genetic mutations
If a patient, however, has the following results, they can be indicative of CML:
- Increased number of WBCs sometimes with a reduced number of RBCs and platelets
- Relatively increased proportion of immature as opposed to mature WBCs
- BCR-ABL1 genetic mutation
How are the Treatments for AML and CML Different?
Since AML is an aggressive disease with a rapid course, it is treated with high-dose chemotherapy. Chemotherapy drugs are indiscriminately toxic to all rapidly dividing cells, including the AML cells. The downside is that healthy body tissues are affected as well, which can cause unpleasant side effects. Chemotherapy is usually given in two phases, an induction phase followed by a consolidation phase.
The induction phase starts right after a confirmed diagnosis of AML has been made. The goal of the induction phase is to rapidly eliminate the immature blasts from the bloodstream and reset their number to normal within the bone marrow. It is a relatively short phase, typically lasting a week.
In younger patients able to tolerate more intensive chemotherapy regimens, a combination of idarubicin (brand name: Idamycin), daunorubicin (brand name: Cerubidine), and cytosine arabinoside (brand name: Cytarabine) may be used. Older patients are usually unable to receive such intensive drugs. Thus, they are treated with milder drugs, such as low-dose Cytarabine, decitabine (brand name: Dacogen), and azacytidine (brand name: Vidaza). Additional drugs may also be used if the patient has certain mutations. For example, in someone with an IDH1 mutation, the IDH1 inhibitor, ivosidenib (brand name: Tibsovo), may be added and for people with the FLT3 mutation, midostaurin (brand name: Rydapt) may be used. Several other drugs may also be used.
Following the induction phase, a consolidation regimen, typically consisting of two to four cycles of chemotherapy is usually given. Each cycle is separated by a period of rest to allow a patient's body to recover and recuperate. The goal of this phase is to eliminate any blast cells that may be lingering after induction chemotherapy.
Depending on the aggression of a patient's disease and their risk for treatment failure, a bone marrow transplant may also be considered.
CML treatment, especially in its most common chronic phase, consists of targeted therapies with Tyrosine Kinase Inhibitors (TKIs). TKIs exploit the unique features of CML cells and weaponize them against it. This way, they can eliminate the cancer cells without harming normal, healthy tissues. For CML, the exploitable feature is the abnormal protein product resulting from the Ph chromosome, BCR-ABL1 tyrosine kinase. TKIs block this enzyme, starving the CML cells of their most important growth signal. Ultimately, the cells are killed off.
There are several TKIs on the market. Those approved as the first line of defense against CML include:
- Imatinib (brand name: Gleevec)
- Dasatinib (brand name: Sprycel)
- Nilotinib (brand name: Tasigna)
- Bosutinib (brand name: Bosulif)
- Ponatinib (brand name: Iclusig)
TKIs, however, are not the only treatment for CML. Chemotherapies and immunotherapies can also be used to treat the disease, and are often combined with TKIs for maximal effect, especially in the advanced phases of CML. Furthermore, these therapies are not curative even though they can control the disease for long periods of time. The only curative treatment for CML is a stem cell transplant which replaced the diseased bone marrow with a healthy one from a donor.
Key Takeaways:
- Acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) are two blood cell cancers that originate in the bone marrow.
- AML is more common than CML, with almost 20,000 cases of AML diagnosed each year in the United States. Only 8,000 cases of CML are diagnosed each year in this country.
- AML is an aggressive disease that progresses fast. CML tends to progress slowly and is typically less aggressive.
- AML is usually treated with high-dose chemotherapy drugs using different regimens divided into phases: the short but intensive induction phase followed by a few rounds of consolidation phase chemotherapy.
- CML is typically treated with targeted therapies called Tyrosine Kinase Inhibitors (TKIs). TKIs block the abnormal protein made by the CML cells, eventually killing them. They are especially effective in the earlier phases of the disease.
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