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Junction Adhesion Molecule family expression as biomarker(s) to predict outcome of patients with acute myeloid leukemia

Summary of the Project

Prognosis of acute myeloid leukemia (AML) is dependent on patient specific characteristics and disease related factors. Estimation of prognosis, at initial diagnosis as well as in the course of the therapy, is used to guide treatment decisions.

Besides cytomorphology, cytogenetics and molecular genetics, flow cytometry (FCM) is an indispensable tool for the initial diagnosis of AML by quantitative and qualitative evaluation of antigen expression and represents an integral component of many scores to predict prognosis. Furthermore, FCM is increasingly used to monitor response to treatment.

In 80-94% of patients, immunophenotypical aberrancies (leukemia associated phenotype LAP) can be detected, which allows a clear distinction from non-malignant hematopoietic cells. The LAP can not only be used to detect, but also to quantify minimal residual disease (MRD). Persistence of MRD as detected by FCM has been shown to be associated with an increased risk of relapse. Clinical trials using MRD detected by FCM as a trigger to increase treatment intensity are ongoing.

We aim here at analyzing the expression of JAM-C, ESAM, JAM4 and JAML by flow cytometry of AML samples at initial diagnosis available in the AML registry. Their expression will be correlated with patient and disease characteristics and associated with outcome. In parallel, the expression will be correlated with response within an ongoing treatment optimization study. Additionally, we will identify patients with longitudinal available samples to quantify the persistence of AML blasts expressing these markers in the course of treatment. The MRD level will be correlated with relapse risk.

Scientific Goals

  • Examine the expression of JAM-C, ESAM, JAM4 and JAML on AML blasts by flow cytometry to further refine individual prognosis at initial diagnosis.
  • Explore these molecules as markers for treatment response and their value to detect MRD.
Surface Expression of proteins of the Junction Adhesion Molecule Family in patients with AML at initial diagnosis

Surface Expression of proteins of the Junction Adhesion Molecule Family in patients with AML at initial diagnosis.

Bone marrow aspirates of patients with newly diagnosed AML were  evaluated for the expression of Junction Adhesion Molecules. Besides classical markers of immaturity (CD34, CD117), cells in the blast gate (SSCloCD45dim) were analyzed for the expression of JAM-C, ESAM and JAM-L. (A) Two representative examples analyzed by multicolor flow cytometry are shown. (B) Proportion and extent of cells in the blast gate expressing JAM-C, ESAM and JAM-L are depicted.
Copyright: Dr. Malte von Bonin

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Prof. Martin Bornhäuser
Director, Dept. of Internal Medicine I, University Hospital Carl Gustav Carus Dresden
Phone: +49 351 458 4704
Email: Martin.Bornhaeuser(at)uniklinikum-dresden.de