Understanding and Treating Leukemia in Children with Down Syndrome

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• Dramatically Increased Leukemia Risk in Down Syndrome
• The Inspiration Behind the Research
• The Critical Link to Chromosome 21
• Relevance for the General Leukemia Population
• Advances in Leukemia Diagnosis and Treatment
• Ongoing Genetic Mysteries in Leukemia Development

Dramatically Increased Leukemia Risk in Down Syndrome

Children with Down syndrome face a profoundly elevated risk of developing leukemia. As Dr. Shai Izraeli, MD, explains, they have two main types of blood cancer. The incidence of myeloid leukemia is 150 times higher, and the incidence of lymphoid leukemia is 20 times higher compared to children without the syndrome. Approximately 3% of all children with Down syndrome will develop leukemia, a stark contrast to the general pediatric leukemia rate of about 1 in 2000 children.

The Inspiration Behind the Research

Dr. Shai Izraeli, MD, describes a pivotal moment in his career that directed his focus toward this unique patient population. After returning from the National Cancer Institute, he encountered a child with both Down syndrome and leukemia. This case captivated him, leading to a night of deep reflection. He recognized the condition as a compelling "experiment of nature" that could unlock broader truths about cancer biology. This personal experience ignited a 16-year research journey dedicated to understanding this complex intersection of genetics and oncology.

The Critical Link to Chromosome 21

The central biological factor is the presence of an extra copy of chromosome 21 in every cell of an individual with Down syndrome. Dr. Izraeli points out a fascinating parallel in general leukemia cases. When examining the chromosomes of leukemia cells from patients without Down syndrome, researchers often find that the most common chromosomal abnormality is also an additional copy of chromosome 21. This suggests that the genetic material on this chromosome plays a crucial, universal role in the development of leukemia, making its study in Down syndrome patients incredibly valuable for all oncology.

Relevance for the General Leukemia Population

The research initiated by Dr. Shai Izraeli, MD, and joined by many global cancer research groups, has proven to have far-reaching implications. Discoveries made by studying leukemia in Down syndrome have provided fundamental insights into how leukemia develops in all patients. The processes uncovered are not isolated to this specific population but are therapeutically important for the broader community fighting blood cancer. This work demonstrates how studying a specific genetic condition can yield universal medical breakthroughs.

Advances in Leukemia Diagnosis and Treatment

The concerted research effort has translated into tangible clinical progress. According to Dr. Izraeli, the work has led to important discoveries that directly impact patient care. These include improved methods for leukemia diagnosis and the development of new treatment strategies. The knowledge gained from understanding the unique biology of Down syndrome leukemia has informed more effective and targeted therapeutic approaches, ultimately improving outcomes for a wide range of leukemia patients.

Ongoing Genetic Mysteries in Leukemia Development

Despite significant progress, key mysteries remain. Dr. Shai Izraeli, MD, admits that the global leukemia treatment community still does not fully understand the precise mechanisms. While many genes on chromosome 21 have been identified as important players in the leukemias of Down syndrome, the exact influence of this chromosome on cancer development is not completely defined. This ongoing puzzle underscores the complexity of cancer genetics and the continuous need for dedicated research, a challenge that Dr. Izraeli finds both humbling and fascinating.

Full Transcript

Dr. Anton Titov, MD: Leading pediatric leukemia expert on unique challenges of blood cancer in kids with Down syndrome. Children with Down syndrome have leukemia 20 to 150 times more often than kids without Down syndrome. How can understanding of leukemia in Down syndrome help in treatment of all child leukemia?

One of your research interests is leukemia that happens in children with Down syndrome. How to treat leukemia in children with Down syndrome?

Dr. Shai Izraeli, MD: As physicians, we sometimes tell other physicians that we should be very open minded. We should look at the "experiment of nature" or "experiment of God." It depends on your values and beliefs. We should see what we can learn from them.

Dr. Anton Titov, MD: Down syndrome is the most common genetic abnormality. It’s not inherited. It's caused by an extra chromosome 21, usually in the egg [oocyte]. But it's the most common genetic disorder.

Dr. Shai Izraeli, MD: I must tell you this personal story. In 2000, I returned from the National Cancer Institute, where I studied a topic related to leukemia. I thought, OK, but now I need to look for some interesting problem that I want to study. This medical problem will be independent from what we did before.

Then I saw a child with Down syndrome and leukemia. I must say, I didn't sleep all night. Because I thought, OK, that's an interesting problem to study.

Dr. Anton Titov, MD: Why is it an interesting problem to study?

Dr. Shai Izraeli, MD: Because children with Down syndrome have a very high rate of leukemia. They have two types of leukemia. There is a type of leukemia that is called myeloid leukemia, and there is a leukemia type that is called lymphoid leukemia.

Children with Down syndrome have 150 times more myeloid leukemia and about 20 times more lymphoid leukemia. About 3% of all children with Down syndrome have leukemia. This is compared with a leukemia rate of 1 in 2000 children without Down syndrome.

This in itself is an interesting problem. But this makes it even more interesting. It made it for me a more interesting problem to study.

Children with Down syndrome have an extra arm of chromosome 21 in every cell of the body. But you look carefully at the chromosomes of leukemias in children without Down syndrome. You also study adults with leukemia.

You will find that the most common chromosomal abnormality is also an additional copy of chromosome 21. Like a child with leukemia, an adult with leukemia may have three copies or four copies of chromosome 21 in their leukemia cells, but not in the body.

I thought that we must understand the leukemia in Down syndrome. Then we may help more children with Down syndrome who have leukemia. But it may be also relevant for the general population with leukemia.

That actually started the research that I've been doing for 16 years already.

Many cancer research groups in the world have joined. I believe we made really important discoveries. We made both fundamental discoveries about how the leukemia develops, what happens in leukemia, what are the processes in leukemia.

But also we made leukemia diagnosis and treatment discoveries that are important for the general population. They are therapeutically important. This has been very exciting leukemia research.

Dr. Anton Titov, MD: Do they relate to particular presence of certain genes and amplified copies on chromosome 21? Or is it some other genetic influences?

Dr. Shai Izraeli, MD: Well, that's really interesting! Because with age, I realize that the older you grow, the less you understand. Every day I learn more about how much I don't understand. It's fascinating!

Because we found many genes that have importance in the leukemias of Down syndrome. But we still actually do not understand precisely what on chromosome 21 influences leukemia development.

When I say "we", I don't mean only our group, my research group. But I mean the global leukemia treatment community.