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Why Does the Risk for MPNs Rise With Age?

Medically reviewed by Mark Levin, M.D.
Written by Maureen McNulty
Posted on January 18, 2022

Myeloproliferative neoplasms (MPNs) develop when certain blood cells undergo gene changes (mutations). These changes cause the cell to begin growing abnormally.

Gene mutations increasingly collect in cells over time, and they become more numerous as a person gets older. Therefore, older adults are more likely to have gene mutations that lead to MPNs than are children or younger adults.

Older Adults Are More Likely To Develop MPNs

Older age is an MPN risk factor. Most people with MPNs are in their 60s and 70s when they are diagnosed. Each type of MPN may affect people at slightly different ages.

Researchers use a term called “median age at diagnosis” to convey when people are generally diagnosed with a condition. The number tells you that half of people with the condition are the median age or older when they are diagnosed.

The median age at diagnosis for different types of MPNs are as follows:

MPNs can affect younger people, but this is not as common. About 12 percent of people with MPNs are under the age of 40.

Certain types of MPNs may be more likely to occur in children or younger adults. For example, about 2 out of 10 people with ET are younger than 41 years old when they are diagnosed, while only 1 out of 10 people with PV are under 40.

MPNs Develop From Gene Changes

In order to understand the link between MPNs and aging, it helps to know how MPNs begin. These conditions develop from cells called hematopoietic stem cells (HSCs).

HSCs typically live in the spongy bone marrow tissue found within certain bones. HSCs are responsible for making all of the different types of blood cells — red blood cells, white blood cells, and platelets.

Like other cells in the body, HSCs carry many different genes. Genes act as instructions that tell each cell when to divide and produce new cells, when to stop growing, and how to carry out different tasks.

Genes occasionally undergo changes. Sometimes, the resulting mutations have no effect on the way a cell operates. Other times, they may cause a cell to behave abnormally.

Gene mutations may cause a cell to grow too quickly or ignore signals telling it to stop dividing. They also can render a cell unable to repair damage. This can make a normal cell change, leading to MPNs or other blood conditions.

Gene Mutations That Cause MPNs

When certain genes become mutated within HSCs, the HSCs stop working properly. They start making too many blood cells, which can go on to cause several problems within the body.

The three classic types of MPNs — primary fibrosis, essential thrombocythemia, and polycythemia vera — are usually caused by mutations in the JAK2, CALR, or MPL genes.

Almost all people with chronic myeloid leukemia have a gene change called the Philadelphia chromosome, in which two different genes become improperly fused together. This leads to a new gene, BCR-ABL1, that encourages cells to grow.

MPN cells also frequently contain additional mutations in genes such as:

  • DNMT3A
  • TET2
  • ASXL1
  • EZH2
  • TP53

These mutations may play a role in which MPN symptoms a person experiences or their disease outlook.

Increasing Gene Mutations Over Time

Gene mutations build up over time. Although an MPN-causing mutation could occur at any point in a person’s life, the chances of this happening rise the more a person ages.

How Do Gene Mutations Occur?

In general, several factors can cause gene mutations. Genes can be damaged when a cell is exposed to things like radiation, ultraviolet light, cigarette smoke, or certain chemicals. Additionally, gene mutations can develop during the process of cell division (when a parent cell divides in order to form two new cells).

During cell division, the parent cell copies its DNA (the substance that contains genes). It then passes on one copy to each of the two new cells. Occasionally, the cell makes a mistake when it is copying a particular gene, leading to a mutation.

Gene Mutations in Blood Cells

Many types of cells don’t typically grow and divide frequently after a person goes through development. However, the body is constantly making new blood cells. HSCs and other immature blood cells go through cell division frequently in order to produce new, mature blood cells.

This means that new mutations are constantly forming and being passed on to other cells. Researchers estimate that by the time a person turns 60, these quickly dividing cells could contain tens of thousands of mutations.

These mutations within blood cells can lead to a condition called clonal hematopoiesis (CH). CH is very common in older adults. It doesn’t cause symptoms, so most people don’t know they have it.

CH occurs when an HSC develops mutations and then goes on to create many copies of itself. This causes a person to have large numbers of blood cells that contain potential MPN-causing gene changes, including JAK2, DNMT3A, and TET2 mutations.

CH is not cancer. However, it leads to an increased risk that a person will develop blood cancers, including MPNs. When a person has CH, it is an indication that they likely have HSCs that contain high-risk gene mutations.

All in all, the older a person gets, the more mutations their blood cells will accumulate. The more mutations a cell contains, the higher the chances that it will turn cancerous.

Talk With Others Who Understand

On myMPNTeam, the social network for people living with myeloproliferative neoplasms and their loved ones, more than 1,800 members come together to ask questions, give advice, and share their stories with others who understand life with MPNs.

Have you been diagnosed with an MPN? Share your experience in the comments below, or start a conversation by posting on your Activities page.

References
  1. Myeloproliferative Neoplasms (MPN) Research Funded by LLS — Leukemia & Lymphoma Society
  2. One Thousand Patients With Primary Myelofibrosis: The Mayo Clinic Experience — Mayo Clinic Proceedings
  3. The Essential Thrombocythemia in 2020: What We Know and Where We Still Have To Dig Deep — Clinical Medicine Insights: Blood Disorders
  4. Survival and Prognosis Among 1545 Patients With Contemporary Polycythemia Vera: An International Study — Leukemia
  5. Cancer Stat Facts: Leukemia - Chronic Myeloid Leukemia (CML) — National Cancer Institute
  6. A Population-Based Study of Chronic Neutrophilic Leukemia in the United States — Blood Cancer Journal
  7. Re-Evaluating the Prognosis and Transformation Risk of Chronic Eosinophilic Leukemia — Blood
  8. Systemic Mastocytosis — Orphanet
  9. Myeloproliferative Neoplasms in the Young: Mayo Clinic Experience With 361 Patients Age 40 Years or Younger — American Journal of Hematology
  10. Myeloproliferative Disorders — UCSF Health
  11. The Genetics of Cancer — National Cancer Institute
  12. Diagnosis, Risk Stratification, and Response Evaluation in Classical Myeloproliferative Neoplasms — Blood
  13. Chronic Myeloid Leukemia — MedlinePlus
  14. Changes in Genes — American Cancer Society
  15. Aging and the Rise of Somatic Cancer-Associated Mutations in Normal Tissues — PLOS Genetics
  16. Germline Risk of Clonal Haematopoiesis — Nature Reviews Genetics
  17. Program Operations Manual System (POMS) — Social Security Administration
  18. Targeting Abnormal Hematopoietic Stem Cells in Chronic Myeloid Leukemia and Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms — International Journal of Molecular Sciences
Posted on January 18, 2022
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Mark Levin, M.D. is a hematology and oncology specialist with over 37 years of experience in internal medicine. Review provided by VeriMed Healthcare Network. Learn more about him here.
Maureen McNulty studied molecular genetics and English at Ohio State University. Learn more about her here.

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