Johanna Ungerstedt

CMML is a heterogeneous group of patients in terms of symptoms and survival, which varies between 0-120 months. On average, patients live for 12 months. In almost all patients, changes in the genome are found, so-called mutations. The most common is mutation in the TET2 gene. We currently have poor tools for assessing an individual patient's prognosis, and little knowledge of how CMML arises. It is likely that a better understanding of the disease's mechanisms of disease would lead to better tools for prognostic assessment. In about 5% of CMML, bone marrow cancer is also present with systemic mastocytosis. It is unclear how these diseases affect each other. We want to increase knowledge about the mechanisms of CMML disease by studying sorted stem cells and mature cells from CMML patients. We study the genome with advanced sequencing technology, in a large international study with patient samples from around the world. We will identify defects in the genome that can cause CMML disease. We also study a small homogeneous group of CMML patients with TET2 mutation, to find out how different blood cells work differently when they have the TET2 mutation compared to normal cells, and a group with systemic mastocytosis and CMML, where we study if the diseases come from the same origin cell. In the end, our studies will lead to increased knowledge about the mechanisms of origin of CMML and how systemic mastocytosis is associated with and affects CMML disease. It is likely that our molecular findings will help to identify new prognostic markers and also identify molecules that can be attacked with new types of treatments. In the long run, this leads to better opportunities to risk assess an individual patient, as well as opportunities to tailor new individualized treatment according to the molecular patterns we find, in this disease with a poor prognosis, where we do not have any good treatment options at present.

Systemic mastocytosis is an incurable bone marrow cancer. Almost all patients have the same point mutation that causes the disease. Despite this, the patients' symptoms are very different. Most people get a nice course but can have a lot of trouble with allergies and diarrhea, while a small proportion of the patients get a rapidly progressing cancer with death within a couple of years. Some suffer directly from the leukemic form of mastocytosis, and some with a mild process suddenly turn into leukemia. What determines the shape of the individual patient, or why some turn into leukemia, is unknown. There is no disease-inhibiting or curative treatment, only symptom relief. We study different types of molecular markers that will hopefully help us to assess risk and prognosis each individual patient. In previous studies, we have found that drugs that affect the packaging form of DNA selectively kill mutated mast cells while normal cells do not die. We now proceed to understand in depth the mechanism for why the drug only kills tumor cells, in order to partly understand how the packaging form of DNA can be involved in the origin of mastocytosis, but also to understand the mechanism of action to start a clinical trial of the drug at systemic mastocytosis. The goal is to find better diagnostic and prognostic markers in order to be able to identify those patients who are at risk of switching to leukemia and those who have serious forms of mastocytosis, so that we can risk assessing each individual patient. The second goal is to understand the mechanism of action of the drugs that selectively kill mutated mast cells, and then initiate a clinical trial where we include those patients with whom we have identified as high-risk patents with our prognostic markers. By extension, with this first targeted treatment, we hope to stop the disease development and improve prognosis and survival in systemic mastocytosis.

Systemic mastocytosis is an incurable bone marrow cancer. Almost all patients have the same point mutation that causes the disease. Despite this, the patients' symptoms are very different. Most people get a nice course but can have a lot of trouble with allergies and diarrhea, while a small proportion of the patients get a rapidly progressing cancer with death within a couple of years. Some suffer directly from the leukemic form of mastocytosis, and some with a mild process suddenly turn into leukemia. What determines the shape of the individual patient, or why some turn into leukemia, is unknown. There is no disease-inhibiting or curative treatment, only symptom relief. We study different types of molecular markers that will hopefully help us to assess risk and prognosis each individual patient. In previous studies, we have found that drugs that affect the packaging form of DNA selectively kill mutated mast cells while normal cells do not die. We now proceed to understand in depth the mechanism for why the drug only kills tumor cells, in order to partly understand how the packaging form of DNA can be involved in the origin of mastocytosis, but also to understand the mechanism of action to start a clinical trial of the drug at systemic mastocytosis. The goal is to find better diagnostic and prognostic markers in order to be able to identify those patients who are at risk of switching to leukemia and those who have serious forms of mastocytosis, so that we can risk assessing each individual patient. The second goal is to understand the mechanism of action of the drugs that selectively kill mutated mast cells, and then initiate a clinical trial where we include those patients with whom we have identified as high-risk patents with our prognostic markers. By extension, with this first targeted treatment, we hope to stop the disease development and improve prognosis and survival in systemic mastocytosis.

Systemic mastocytosis is an incurable bone marrow cancer. Almost all patients have the same point mutation that causes the disease. Despite this, the patients' symptoms are very different. Most people get a nice course but can have a lot of trouble with allergies and diarrhea, while a small proportion of the patients get a rapidly progressing cancer with death within a couple of years. Some suffer directly from the leukemic form of mastocytosis, and some with a mild process suddenly turn into leukemia. What determines the shape of the individual patient, or why some turn into leukemia, is unknown. There is no disease-inhibiting or curative treatment, only symptom relief. We study different types of molecular markers that will hopefully help us to assess risk and prognosis each individual patient. In previous studies, we have found that drugs that affect the packaging form of DNA selectively kill mutated mast cells while normal cells do not die. We now proceed to understand in depth the mechanism for why the drug only kills tumor cells, in order to partly understand how the packaging form of DNA can be involved in the origin of mastocytosis, but also to understand the mechanism of action to start a clinical trial of the drug at systemic mastocytosis. The goal is to find better diagnostic and prognostic markers in order to be able to identify those patients who are at risk of switching to leukemia and those who have serious forms of mastocytosis, so that we can risk assessing each individual patient. The second goal is to understand the mechanism of action of the drugs that selectively kill mutated mast cells, and then initiate a clinical trial where we include those patients with whom we have identified as high-risk patents with our prognostic markers. By extension, with this first targeted treatment, we hope to stop the disease development and improve prognosis and survival in systemic mastocytosis.