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How and Why Do MPNs Transform?

Posted on November 29, 2021
Medically reviewed by
Mark Levin, M.D.
Article written by
Maureen McNulty

Myeloproliferative neoplasms (MPNs) are disorders that affect different types of blood cells. Doctors consider MPNs to be a form of cancer. However, these disorders are often slow-growing compared to other types of cancer.

In some cases, MPNs can turn into leukemia, a faster-growing blood cancer. Additionally, less aggressive types of MPNs can change into a more aggressive type. This process is called transformation. Leukemic transformation often leads to a much worse prognosis for people with MPNs.

To learn more about transformation and what it means for people with MPNs, myMPNteam talked to Dr. Naveen Pemmaraju, a physician and researcher who specializes in hematology/oncology. Dr. Pemmaraju is an associate professor in the Department of Leukemia at the University of Texas MD Anderson Cancer Center.

What Types of Cancers Do MPNs Transform Into?

When MPNs transform, they turn into acute myeloid leukemia (AML). AML that develops from another disorder, including MPNs, is called secondary AML. This is different from primary AML, which develops on its own without a clear cause. Doctors may also call secondary AML by other names, including blast-phase MPN or post-MPN AML.

The main difference between MPNs and acute leukemias is the number of abnormal cells in the body. Normally, hematopoietic stem cells in the bone marrow (the soft tissue found inside certain bones) make all of the body’s healthy blood cells. MPNs are a collection of blood disorders that are caused by mutations in bone marrow stem cells. In some cases, abnormal stem cells may create blast cells (immature versions of the body’s blood cells). Doctors call it leukemia when blast cells make up at least 20 percent of the cells in the bone marrow or peripheral blood (the blood circulating throughout the body).

One type of MPN can also transform into another. In particular, polycythemia vera (PV) and essential thrombocythemia (ET) sometimes transform into myelofibrosis (MF). Like AML, myelofibrosis can be divided into primary or de novo MF, which develops on its own, or secondary MF, which develops from PV or ET. Both primary and secondary myelofibrosis cause similar signs, and symptoms are treated the same way and lead to similar outcomes. “The differences are not very clear in all people,” said Dr. Pemmaraju.

It is important to remember that your condition may change over time. As Dr. Pemmaraju noted, “Whatever you start with, for some of these blood cancers, that may not be what you end up with.”

How Often Do MPNs Transform?

Any type of MPN can transform into leukemia. The three classic types of MPNs transform at different rates:

Other types of MPNs may also transform. Chronic neutrophilic leukemia (CNL) and chronic eosinophilic leukemia both turn into AML at higher rates. Additionally, about 1 out of 20 people with chronic myeloid leukemia (CML) will develop an aggressive form of the disease called blast phase or blast crisis CML. This phase can be similar to either AML or acute lymphoblastic leukemia (ALL).

Why Do MPNs Sometimes Transform?

Scientists are still studying how MPNs can turn into AML. “There’s not much known about the exact reasons, but there are some theories and hypotheses,” reported Dr. Pemmaraju.

In many cases, MPNs transform because of a specific event or exposure. “One hypothesis is what you would expect: that there’s some selective pressure, environmental exposure, cancer, or chemo exposure that presses the body to go in that direction,” Dr. Pemmaraju explained. Things like chemotherapy, radiation therapy, or exposure to certain chemicals can increase the risk of developing AML.

“There’s a second theory that maybe folks are destined to have more than one blood cancer to begin with,” Dr. Pemmaraju elaborated. Some people have certain gene changes in their stem cells that can make blood cancers more likely to develop. These gene changes may cause certain conditions, like MPNs, and then later lead to leukemia.

It’s not always clear whether a case of AML developed as the result of a first condition, such as an MPN. “Is that a secondary AML that’s arisen out of something, or did that happen on its own?” asked Dr. Pemmaraju. “These are the kinds of discussions we’re having.”

Risk Factors for MPN Transformation

Not everyone with an MPN has the same risk of experiencing leukemic transformation. People who have a higher chance of transformation may need to be monitored and undergo tests more often than those who have a lower chance.

Doctors sometimes use prognostic systems to determine the chances that an MPN will transform. These systems consider a person’s risk factors and assign a risk level. This information helps doctors make treatment decisions and predict outlooks, including a person’s chances of developing acute leukemia. “With myelofibrosis, we can stratify patients who are low-risk, intermediate-1 risk, intermediate-2 risk, and high risk,” said Dr. Pemmaraju. “You can figure out who is at a higher risk to transform to AML and who isn’t, and you can follow those patients more closely.”

For those with PMF, certain characteristics can make a person more likely to undergo leukemic transformation. These include:

  • Being male
  • Age 70 years old or older
  • Experiencing certain symptoms such as weight loss, fever, or night sweats
  • Having a higher number of immature blast cells in the blood
  • Being diagnosed with severe anemia (low levels of red blood cells)
  • Having certain genetic changes, including mutations in the genes IDH1, ASXL1, RUNX1, CEBPA, and SRSF2

Risk factors that lead to a higher chance of transformation for people with ET include:

  • Advanced age
  • Severe thrombocytosis (high platelet count)
  • Leukocytosis (high white blood cell levels)
  • Anemia
  • Changes in the EZH2 or TP53 genes

PV is more likely to lead to leukemia in people who are older than 61 years of age. Transformation is also more common in those who have:

  • Leukocytosis
  • A history of being treated with Leukeran (chlorambucil), Vercite (pipobroman), or radiation treatments
  • A complex karyotype (too many or too few chromosomes — the long pieces of DNA that hold a cell’s genes)
  • Mutations in the IDH2 or SRSF2 genes

Can You Prevent MPNs From Transforming?

Current treatments for MPNs can’t prevent leukemic transformation. However, having regular follow-up visits may help catch leukemia early. “The answer is vigilance. If you have one type of blood cancer, have a plan with your doctor to be monitored for the development of others,” Dr. Pemmaraju explained.

If tests show that a person has developed leukemia, other treatments may be able to help. Doctors may recommend aggressive treatment options like chemotherapy or stem cell transplants. These approaches may help a person go into remission, in which some or all signs of cancer disappear.

Dr. Pemmaraju said, “The key is, you don’t want to lose touch with your physician or your treating team no matter what type of MPN you have because at some point, any of these could transform to AML.”

Talk With Others Who Understand

By joining myMPNteam, the social network and online support group for those with MPNs, you gain a community of people who understand the challenges of living with these rare blood cancers. On myMPNteam, more than 1,800 members come together to ask questions, give advice, and share their stories with others who understand life with MPNs.

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

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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