“Preleukemia” was a term doctors previously used for myelodysplastic syndrome (MDS). Some people with MDS go on to develop acute myeloid leukemia (AML), so doctors sometimes used to view MDS as the first stage of AML. Doctors have found that other conditions and gene changes — including clonal hematopoiesis of indeterminate potential (CHIP) — can also lead to a higher risk of leukemia. MDS and CHIP are not unique in this way. As a result, doctors now view these disorders as separate conditions, and experts no longer refer to MDS as preleukemia.
The majority of people with MDS or other preleukemic conditions do not ever develop leukemia. However, MDS can affect blood-cell levels and may require treatment.
How Does Leukemia Develop?
Leukemia begins in the bone marrow (spongy tissue found inside certain bones). Within the bone marrow are many immature cells called stem cells and progenitor cells. The immature cells form the different types of blood cells: red blood cells, white blood cells, and cells that make platelets.
Sometimes, gene changes occur in a blood cell or bone marrow cell. The gene changes can turn a cell cancerous, making it grow out of control and produce many copies of itself. These leukemia cells are abnormal and can’t carry out their usual jobs within the body. They also crowd out healthy cells in the bone marrow, leading to lower levels of normal blood cells.
What Is Myelodysplastic Syndrome?
Doctors may identify signs in a person’s blood cells that could indicate a higher risk of developing blood cancer. Precancer and preleukemia signs are complex, and many different factors determine an individual’s actual risk of developing leukemia. There are scoring systems doctors can use to help define this risk.
Change in Terms
There are a couple of reasons that doctors no longer use the term preleukemia to describe MDS. For one, MDS does not lead to leukemia for the majority of people: About 3 out of 10 people with MDS go on to develop AML. Additionally, many people with AML do not have MDS before being diagnosed with leukemia. MDS is not simply the first step to developing leukemia. Other factors determine whether a person develops AML.
Doctors also don’t call MDS preleukemia because the cancer cells from the conditions often act differently from each other. Additionally, cells from these two diseases tend to have different gene changes. Experts now often view MDS as a separate type of cancer rather than just the first phase of AML.
Other Potential Leukemia Precursor Disorders
Several other blood disorders are sometimes called “precursor states” or “premalignant,” meaning they can occur before a person develops leukemia. These conditions are not considered to be cancer. People who develop them usually have a good prognosis and show few signs and symptoms of disease.
A person’s chances of developing a blood cancer from these conditions are very slim. Additionally, many people who develop blood cancers have no history of these conditions. The link between these conditions and leukemia is so small that experts do not often consider these conditions to be preleukemia.
Clonal Hematopoiesis of Indeterminate Potential
CHIP occurs when immature stem or progenitor cells develop one or more gene mutations that are sometimes found in cancer. The cells then make mature blood cells that also contain this mutation. None of these cells are cancerous, but they may potentially become cancerous in the future. CHIP is more common in older adults. About 10 percent of people between the ages of 70 and 80 have CHIP. Each year, between 0.5 percent and 1 percent of people with CHIP develop MDS, AML, or other types of blood cancer.
Preleukemic Gene Changes
Sometimes, a person’s stem cells develop gene mutations. If the person later develops AML, these same gene changes are then seen in their cancer cells. This makes researchers believe that some of these gene mutations are preleukemic, causing the stem cells to produce cancerous blood cells.
Preleukemic gene changes are more likely to happen as a person ages. More than 1 percent of older adults have preleukemic changes. However, the majority do not develop blood cancer.
What Causes MDS and CHIP?
Leukemia, MDS, and precursor conditions are all linked to changes in a cell’s genes. Some of these changes are inherited mutations. They are present in all of a person’s cells at birth. Other gene changes — acquired mutations — form in individual cells over the course of a person’s life. Most gene changes that cause leukemia are acquired mutations. They develop when a cell’s genes become damaged. Certain risk factors known to cause gene mutations have been linked to higher risks of developing different types of cancer.
MDS occurs when abnormal stem cells make defective blood cells. People with MDS experience low blood cell counts and have at least one blood cell type that looks abnormal and acts abnormally.
Risk factors that increase a person’s likelihood of developing MDS include:
- Older age (60 or above)
- Exposure to chemicals at work, including benzene or pesticides, or to radiation
- Exposure to heavy metals, such as mercury or lead
- Exposure to tobacco smoke
- Cancer treatment, such as chemotherapy or radiation therapy
Researchers only began studying CHIP within the past decade, so they don’t yet fully understand all of the risk factors that may lead to the condition. Old age appears to be one, since CHIP is seen in older adults. Additionally, exposure to chemicals, radiation, or tobacco smoke may increase a person’s chances of developing CHIP.
Symptoms of MDS and CHIP
Myelodysplastic syndrome can lead to different symptoms depending on which type of blood cell is affected. MDS symptoms include:
- Anemia — Low numbers of red blood cells, which can cause tiredness, loss of appetite, breathing problems, pale skin, and a rapid heartbeat
- Neutropenia — Low levels of white blood cells, which can lead to fevers and frequent infections
- Thrombocytopenia — Low platelet count, which often causes bruising, bleeding problems, and petechiae (tiny purple, red, or brown spots on skin, which may be more difficult to see on darker skin)
CHIP doesn’t come with any signs or symptoms. People with this condition don’t typically feel any different, and their blood tests may look normal. Many people with CHIP don’t know they have it until they go through genetic testing related to some other disease.
Treatment for MDS and CHIP
People with MDS may not need treatments if they aren’t experiencing many signs or symptoms. However, if a person has low blood cell levels that are causing health problems, they may need to begin treatment. A doctor will recommend a treatment plan based on the person’s age, health, preferences, type of MDS, and risk level of the MDS.
Treatments can include:
- Supportive care treatments, including blood transfusions (receiving healthy blood cells from a donor) or growth factors (molecules that encourage the body to make more blood cells)
- Chemotherapy drugs, such as decitabine (Dacogen) and azacitidine (Onureg)
- Medications that affect the immune system, including lenalidomide (Revlimid)
- Stem cell transplant, a procedure that includes some risks and side effects but can cure MDS for some people
There are no treatments for CHIP. However, people with CHIP should get blood tests every three to six months. This way, if CHIP transforms into leukemia, it will be caught early.
Talk With Others Who Understand
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Are you living with MDS, CHIP, or another disorder your doctor has described as preleukemic? Share your experiences in the comments below, or start a conversation by posting on your Activities page.
References
- Preleukemia: One Name, Many Meanings — Leukemia
- Leukemia — Cleveland Clinic
- Precancerous — National Cancer Institute
- Does Pre-Cancer Mean I’m Going To Get Cancer? — Cancer Treatment Centers of America
- Myelodysplastic Syndromes Treatment (PDQ) — Patient Version — National Cancer Institute
- What Is MDS? — MDS Foundation
- Myelodysplastic Syndrome Is Not Merely “Preleukemia” — Blood
- Clonal Hematopoiesis of Indeterminate Potential and Its Distinction From Myelodysplastic Syndromes — Blood
- Clonal Hematopoiesis of Indeterminate Potential — Deutsches Ärzteblatt International
- Monoclonal B-Cell Lymphocytosis and Early-Stage Chronic Lymphocytic Leukemia: Diagnosis, Natural History, and Risk Stratification — Blood
- To Catch a Pre-Leukemia — Science Translational Medicine
- Preleukemia: The Normal Side of Cancer — Current Opinion in Hematology
- Changes in Genes — American Cancer Society
- Myelodysplastic Syndromes — Mayo Clinic
- Monoclonal B-Cell Lymphocytosis: Update on Diagnosis, Clinical Outcome, and Counseling — Clinical Advances in Hematology & Oncology
- Symptoms — The Aplastic Anemia and MDS International Foundation
- What Is Clonal Hematopoiesis of Indeterminate Potential (CHIP)? — Dana-Farber Cancer Institute
- New Insights Into Monoclonal B-Cell Lymphocytosis — BioMed Research International
- General Approach to Treatment of Myelodysplastic Syndromes — American Cancer Society
- Monoclonal B-Cell Lymphocytosis (MBL) — Lymphoma Australia
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