AML vs. CML: What Are the Differences?

Acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) have key differences. The speed of disease progression in CML vs. AML is one way the two conditions are distinct, but they also differ in some of their symptoms, and in how they are diagnosed and treated.

AML is classified by subtypes, while CML is classified by phases. In AML, the disease comes on quickly, and without treatment, the affected person tends to decline rapidly. With CML, the condition comes on slowly and worsens over time. AML is far more common, affecting both kids and adults, while CML primarily affects older people.

This article will help you learn what sets AML apart from CML. It also discusses CML vs. AML treatment options.

Symptoms

It's not always easy to distinguish between acute and chronic myeloid leukemia based on symptoms alone. The two conditions can have similar symptoms, including:

• Tiredness
• Weakness
• Fever

However, there can also be differences as well. With acute myeloid leukemia, patients may also experience symptoms such as:

• Feeling short of breath
• Bruising easily
• Loss of appetite with potential weight loss
• Petechiae (pinpoint spots underneath the skin caused by bleeding)
• Bone pain
• Frequent infections
• Painless lumps on the body

Meanwhile, those with chronic myeloid leukemia may experience symptoms such as:

• Unexplained weight loss
• Night sweats
• Full feeling on the left side below the ribs

Sometimes, people with CML don't have any symptoms.

Causes

AML and CML have different causes. AML happens when a genetic mutation makes the body produce too many white blood cells, while CML is caused by abnormalities in a single chromosome that lead to the overproduction of a certain protein.

Acute Myeloid Leukemia

With acute myeloid leukemia, a mutation in the stem cells causes more white blood cells to be produced than are needed. These cells are immature (not maturing beyond the early blast stage) and lack the infection-fighting capabilities of fully developed white blood cells.

As the number of immature blast cells increases, this leaves less room for red blood cells (which carry oxygen) and platelets (which help in clotting). When these healthy cells are crowded out, it gives rise to AML leukemia symptoms.

It is not known why this mutation develops, but it is known that both smoking and prolonged exposure to the chemical benzene might put you at increased risk.

AML is defined by its subtypes, rather than with staging as is used in other types of cancer. The subtypes are based on the genetic changes involved. The standard subtypes identified by the World Health Organization are:

• AML with myelodysplasia-related changes
• AML related to previous chemotherapy or radiation
• Myeloid sarcoma (also known as granulocytic sarcoma or chloroma)
• Myeloid proliferations related to Down syndrome

Three other subtypes that can be divided into further categories include:

• AML with chromosomal translocations and inversions
• AML not otherwise specified
• Undifferentiated and biphenotypic acute leukemias

Chronic Myeloid Leukemia

In many cases of chronic myeloid leukemia, some DNA between chromosomes 9 and 22 is partially swapped in a process known as translocation. In almost all CML patients, this makes chromosome 22 shorter than usual—something dubbed the Philadelphia chromosome.

This also leads to the formation of the BCR-ABL oncogene, which produces a protein that causes CML cells to grow and divide uncontrollably. These DNA changes are not passed to you from your parents (inherited) but rather occur during your lifetime.

CML cells mature more than AML cells do. While these more closely resemble normal white blood cells, they don't fight infection as well. They also end up crowding out normal cells from the bone marrow.

With CML, it can take much longer for the condition to cause problems. The progression is defined by phases. They include:

• Chronic phase, which can last for years. During that time, the makeup of blood and bone marrow contains less than 10% blast cells.
• Accelerated phase, with higher counts of blasts and often with new genetic changes.
• Blast phase, with a fever, enlarged spleen, and other symptoms due to high blast counts.

Without treatment, CML takes about three to four years to transition from the chronic to blast phase.

Comparing CML vs. AML

Besides distinct causes and differing symptoms, the speed of disease progression is different in AML than in CML. AML symptoms come on quickly over days to weeks. With CML, the symptoms come on much more slowly, over months to years.

The most important differences between the two conditions are as follows:

Diagnosis

Determining whether you may have either AML or CML will mean undergoing a battery of tests. With CML, there may be no symptoms. Instead, it may be flagged during a routine checkup or a blood test done for something unrelated.

For both AML and CML, you can expect to undergo blood, bone marrow, and genetic tests such as the following:

• A complete blood count
• A peripheral blood smear
• Bone marrow aspiration and biopsy
• Chromosome and gene studies, which may include cytogenetics, fluorescent in situ hybridization (FISH), and polymerase chain reaction (PCR) tests

AML Testing

When diagnosing AML, some factors that healthcare providers may look for in the lab samples include:

• Leukemic blast cells in the bone marrow
• An increased percentage of blast cells in the marrow
• Unique antigen markers on the blast cell surface, such as cluster designation (CD)13 or (CD)33

CML Testing

In looking for a case of CML, healthcare providers are on alert for:

• An increased white blood cell count together with reduced red blood cell numbers and a possible decrease in platelets
• Any changing proportion of fully mature white blood cells to immature ones
• The type of blood cells and their size and shape
• Signs of the BCR-ABL1 gene, which can sometimes be identified by the FISH test or in other cases may require a more sensitive quantitative polymerase chain reaction test to find

As part of the diagnostic process, healthcare providers will determine the phase of the disease (in the case of a CML diagnosis) or classify the subtype (in the case of AML).

Treatment

Finding the right treatment for your particular type of leukemia is key because approaches can vary.

AML Approaches

Chemotherapy is the primary treatment for those diagnosed with AML. This involves the use of drugs to kill cancer cells, in most cases by interfering with their ability to divide and grow. Chemotherapy will likely be divided into two phases: induction and consolidation.

Induction therapy takes place right after diagnosis, aiming to put you into complete remission. In younger people, a combination of Cytosar-U (cytarabine) and Cerubidine (daunorubicin) or Idamycin (idarubicin) is commonly given.

Older adults with conditions that rule out the use of intensive chemotherapy may be given lower intensity therapies, such as:

• Dacogen (decitabine)
• Vidaza (azacitidine)
• Low dose cytarabine

These therapies may be used alone or in combination with Venclexta (venetoclax), a BCL2 inhibitor, or Tibsovo (ivosidenib), an IDH1 inhibitor, if mutations are present.

Consolidation therapy is done by giving different medications following induction therapy to mop up any lingering AML cells that may not have been detected. Younger patients are often given two to four rounds of at least an intermediate dose of an agent like cytarabine.

As part of the therapy, particularly for those at higher risk of relapse, a stem cell transplant is often suggested.

In some AML cases, targeted therapy aimed at specific genes or proteins or even the environment of the tissue itself may be an option. This can target mutations in genes such as IDH1, IDH2, and FLT3.

Radiation therapy, in which cancer cells are destroyed by beams of X-rays or other particles, tends to be given only in select cases as it would not target the AML cells circulating in the blood. This may involve cases in which AML has spread to the brain or where a specific tumor needs to be shrunk.

CML Therapy

The usual treatment for the majority of people with CML is targeted therapy, with other options such as chemotherapy, immunotherapy, and bone marrow (stem cell) transplantation used much less often than they were in the past.

CML is sometimes called the "good" cancer because CML treatments have advanced, including targeted therapy drugs. The targeted approach for CML patients takes aim at the BCR-ABL tyrosine kinase enzyme, with the idea of inhibiting this protein.

When tyrosine kinase inhibitors are used, these keep the BCR-ABL enzyme from working and kills off CML cells. These usually come in pill form. Some tyrosine kinase inhibitors that may be offered to those with CML include the following:

• Gleevec (imatinib): Approved in 2001, this was the first targeted therapy for CML.
• Sprycel (dasatinib): This can be used either as an initial treatment or substituted for other drugs that are not working.
• Tasigna (nilotinib): This agent is another initial option or a possibility if another targeted medication is not working.
• Bosulif (bosutinib): This medication is offered to those experiencing a lot of side effects or in cases where other targeted agents are not effective.
• Iclusig (ponatinib): Those on this medication have the T3151 mutation and have not had luck with other agents, either finding these ineffective or experiencing a large number of side effects.

Chemotherapy may also be a possibility in some CML cases with Droxia or Hydrea (hydroxyurea). This may be used initially to normalize blood cell levels and also reduce spleen size. The downside is that this alone does not prevent blasts from developing, and it also doesn't reduce the number of cells with Philadelphia chromosome.

Another option may be immunotherapy, which relies on the body's own immune system to destroy the cancer. The immunotherapy agent interferon, given by an injection under the skin, can help lower white blood cell counts and, in some cases, can reduce those cells with the Philadelphia chromosome.

Stem cell transplantation (formerly called bone marrow transplantation) may be an option for some CML patients. With this, bone marrow with leukemia is replaced by hematopoietic (blood-producing) stem cells, which have the ability to develop into normal bone marrow. These can either come from your own stem cells or be donated by someone else.

Prevention

Heading off AML or CML before it develops can be an appealing idea. Unfortunately, for CML, there are no known lifestyle risk factors that can be altered.

With AML, most of those affected do not have any lifestyle risk factors that can be changed. Quitting smoking is one of the few actions that may have a preventive effect. Also, your risk may be lowered by avoiding the cancer-causing chemical benzene. However, this is likely a risk factor for AML in only a few cases.

Some rare cases of AML occur after a person has a different type of cancer that is treated with chemotherapy or radiation. The healthcare provider will weigh the need for treating this other cancer with the slightly increased risk that it may result in AML.

Summary

AML and CML are blood and bone marrow cancers that affect the same lines of white blood cells. AML comes on suddenly as very immature cells crowd out normal cells in the bone marrow. CML comes on more slowly, with the CML cells growing out of control.

AML is vigorously treated upon detection with chemotherapy and stem cell transplantation. CML is primarily treated with targeted therapy, but may also be treated with chemotherapy, immunotherapy, or stem cell transplantation.