Exosomes as new markers in risk stratification of pediatric acute leukemia

Acute leukemia is the most common childhood cancer form. Acute lymphoblastic leukemia (ALL) is the most frequent sub-type, while acute myeloblastic leukemia (AML) is rarer and also more difficult to treat. Leukemia is primarily treated with chemotherapy, and treatment response is evaluated by “minimal residual disease” (MRD), a measure of remaining leukemic cells in bone marrow or blood. These have strong prognostic value. Around 80 % of pediatric AML patients respond to treatment, but 50 % of these patients will later relapse and die. Within the ALL group around 15 % of children that initially respond to treatment will relapse. This underscores the need for improved early detection of remaining leukemic cells in blood or bone marrow.

The current method of monitoring MRD in the bone marrow is an invasive procedure in general anaesthesia. Assessing MRD in blood could provide earlier information of treatment failure, and represent a less invasive method. Non-invasive biomarkers currently explored in context of cancer in general include cytokines, circulating cell-free nucleic acids, microRNA, and exosomes.

            Exosomes are 50 – 100 nm sized vesicles originating from within cells, are produced by most cell types, and are found in all extracellular fluids. They are found in higher abundance in blood of cancer patients, and are now increasingly exploited as non-invasive cancer biomarkers. Potentially, presence of exosomes in plasma can predict the leukemic burden, even when leukemic blasts are not detectable in circulation. The fact that exosomes may mirror their cell of origin implies that they are attractive surrogates for early detection of cancer cells. 

            The aim of this project is to define whether exosomes may represent a biomarker allowing earlier information of treatment response and relapse.

            

Objectives

1. Precise identification and quantification of leukemia-derived exosomes from blood plasma

2. Analyze the predictive value of exosomes as markers for MRD

 

Main methods

Blood plasma samples has been sampled from pediatric ALL and AML patients since 2016 at Oslo University Hospital. Samples have been taken at time of diagnosis, at different time points during treatment when treatment response is evaluated, and at the end of treatment. Patients are still recruited to this project, which has been approved by the Regional Ethical Committee.

The student’s main task will be to establish the technology and methodology to precisely identify, quantify, and phenotype exosomes at single exosomal level in plasma samples.

 

 The student will get full tuition in the all methods, which includes:

  • Isolation of blood plasma from patient blood samples
  • ”Multi-color” flow cytometry
  • ImageStream (hybrid between flow cytometer and confocal microscopy)
     - > main method for the project
  • Proteomics (MS)

 

The student’s responsibilities

We expect that the student will read up on relevant literature, take part in the group’s regular project and literature meetings, and regularly present the projects in internal project meetings and at national/international meetings if relevant.

 

About the research group and environment

The student will be part of the “Innate Lymphocyte Research Group” headed by Marit Inngjerdingen at Department of Immunology, Rikshospitalet, Oslo University Hospital. The research group focuses primarily on NK cells and leukemia. Involved in the project is also a PhD student (a pediatric oncologist). The group currently consists of 1 PhD student, 1 post doc, 1 physician, and 2 technicians.

 

Contact information:

You are welcome to contact Marit Inngjerdingen for further information:

Marit Inngjerdingen, e-mail: mainng@rr-research.no; +4795063929/+4723073769

Published Mar. 22, 2018 10:28 AM - Last modified Apr. 19, 2018 8:13 AM

Supervisor(s)

Scope (credits)

60