Child acute lymphoblastic leukemia. Causes. Diagnosis and new treatment options. 3

Child acute lymphoblastic leukemia. Causes. Diagnosis and new treatment options. 3

Child acute lymphoblastic leukemia. Causes. Diagnosis and new treatment options. 3

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Precision medicine offers new molecular insights into pediatric leukemia diagnostic and treatment options. Leading child leukemia expert explains how breakthrough leukemia therapy is being developed in research and in clinical trials. Leukemia, especially acute lymphoblastic leukemia happens more frequently in children with Down syndrome. Dr. Anton Titov, MD. You study leukemia in children with Down syndrome. Dr. Anton Titov, MD. What are the implications of your research for children with leukemia who do not have Down's syndrome? Dr. Shai Izraeli, MD. It's worthwhile to talk about two aspects of leukemia. There are two major findings from the story of leukemia in Down syndrome. Major finding #1 that is generally relevant to childhood leukemia is this. Extra chromosome 21 affects normal blood development during the fetal stage, in the embryo. Normal blood development becomes abnormal. Dr. Shai Izraeli, MD. It predisposes the children with Down syndrome to leukemia. Dr. Anton Titov, MD. Why is it? I can go to details, but I don't think we should go to details. But why is this important? Because we know today that childhood cancer in general, and childhood leukemia in particular, already arises in the fetus. Leukemia already exists in the developing embryo. We know today that leukemia in children is actually an accident. It's a developmental accident. It's an accident in normal development. OK? It's bad luck. in Down's syndrome this extra chromosome 21 affects the normal development of blood cells. We think, and we have a lot of basis to say this. Extra chromosome 21 affects the development of leukemia. this is one important finding. The second important finding is this. Dr. Shai Izraeli, MD. We found that the acute lymphoblastic leukemia of Down syndrome has a specific type of genetic mutation in a specific signalling molecule. I will explain it in a more simple terms. It is a mutation that gives a lot of fuel to the engines of the cell. cells proliferate and grow. We found that this abnormality is not unique to leukemia. It is found also only in about 5 to 10% of children and adults with leukemia. These are patients who do not have Down syndrome. Dr. Anton Titov, MD. Why is it important? Because there is a cancer medication that blocks this signaling. now there is a clinical trial in over 200 institutions around the world. In the Children Oncology Group in the United States there is an experiment happening. There is a clinical trial with a cancer medication against this type of leukemia. Dr. Shai Izraeli, MD. Many people call such leukemias Philadelphia-like leukemias in children and adults without Down syndrome. Paradoxically, children with Down syndrome are not allowed to participate in these clinical trials. Because clinical trials usually exclude children Down syndrome. But a very general discovery of a very bad subtype of leukemia resulted from our research. It was our research of leukemia and Down syndrome. We are now trying to cure this leukemia with targeted cancer therapy. By "we", I mean the whole leukemia treatment community. we have found the driving force of leukemia in about 60 to 70% of the leukemias in Down syndrome. This caner mutation is the fuel that drives the cancer engine. Sometimes you think that the leukemic cells are like a car. the driver, or this gasoline, is activation of a signaling pathway. In professional words we call it JAK / STAT pathway. we published on importance of JAK STAT for leukemia in Down syndrome. Then other groups found JAK/STAT mutation also in children and adults with leukemia who do not have Down syndrome. We also found this mutation. in Down syndrome, 60 or 70% of all cases of acute lymphoblastic leukemia have this mutation. ALL is acute lymphoblastic leukemia. There are children, adults, and adolescencents without Down syndrome, who have acute lymphoblastic leukemia. They have JAK/STAT mutation frequency between 5 to 15%. But it's the same leukemia. And it's a very bad type of leukemia. Dr. Shai Izraeli, MD. I said before that we are now in a very good era in treatment of leukemia. Because we cure most of the leukemia patients. We want to cure all of the patients with acute lymphoblastic leukemia. Therefore we have to focus on high-risk leukemia. The subtype of these leukemias that we identified in Down syndrome [ALL] is a high risk leukemia subtype. Therefore, there are efforts to develop specific inhibitors of this cancer-causing pathway. One of these inhibitors is currently in a clinical trial in the United States in the Children Oncology Group. I think that they have more than a 100 or 200 different hospitals participating in this clinical trial. It's very important at this stage. A child might have an acute lymphoblastic leukemia. Then this patient must be involved in a clinical trial. Because we really don't know if this treatment will work. Dr. Shai Izraeli, MD. We find often that cancer cells are very tricky. I compare it always to policemen and thieves. Dr. Anton Titov, MD. You close the door, and they enter through the window. we don't know if a new cancer therapy against leukemia will help. But I am very encouraged. We made our discoveries in 2008. About 9 years later there have been already clinical trials with inhibitors to this acute lymphoblastic leukemia treatment. it's very emotionally exciting!

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