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ABSTRACTS – ORAL PRESENTATIONS - AMCA, spol. s r.o.

ABSTRACTS – ORAL PRESENTATIONS - AMCA, spol. s r.o.

ABSTRACTS – ORAL PRESENTATIONS - AMCA, spol. s r.o.

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to employ flow cytometry for estimation of the number of particular DNA sequences on<br />

chromosomes of interest. The numerous and important contributions to the analysis<br />

of complex plant genomes document how fruitful and happy the marriage between<br />

flow cytometry and plant genomics has been. Considering the recent methodological<br />

advances, one may expect that this relationship will flourish even more than before.<br />

18. THE PLANAR CELL POLARITY PATHWAY DRIVES PATHOGENESIS OF CHRONIC<br />

LYMPHOCYTIC LEUKEMIA BY THE REGULATION OF B-LYMPHOCYTE MIGRATION<br />

Markéta Kaucká 1 , Šárka Pavlová 2,3 , Pavlína Janovská 1 , Karla Plevová 2,3 , Lucie Poppová 2,3 ,<br />

Hana Mádrová 2,3 , Jan Verner 2 , Jiřina Procházková 1 , Šárka Pospíšilová 2,3 , Alois Kozubík 1,4 ,<br />

Gunnar Schulte 1,5 and Vítězslav Bryja 1,4<br />

1<br />

Institute of Experimental Biology, Faculty of Science, Masaryk University, Kotlářská 2,<br />

611 37, Brno, Czech Republic; bryja@sci.muni.cz<br />

2<br />

Center of Molecular Biology and Gene Therapy, Department of Internal Medicine–<br />

Hematology and Oncology, University Hospital Brno and Medical Faculty MU, Brno,<br />

Czech Republic<br />

3<br />

CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech<br />

Republic<br />

4<br />

Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech<br />

Republic, Brno, Czech Republic<br />

5<br />

Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden<br />

Chronic Lymphocytic Leukemia (CLL) is the most common form of leukemia in<br />

Western countries found in adults. CLL is characterized by monoclonal expansion and<br />

accumulation of functionally incompetent B lymphocytes. Most patients are diagnosed<br />

with no symptoms using a routine blood test that shows a high white blood cell count.<br />

CD5 + lymphocytes show impaired migration and often invade into such organs as<br />

lymph nodes, spleen, liver and bone marrow which results in disrupted organ function,<br />

hematopoiesis (anemia) and weaken immunity. The prognosis of patients with CLL varies<br />

widely at diagnosis and the pathology of CLL remains still unclear.<br />

In our study, we show that core components of Wnt/planar cell polarity (PCP) pathway<br />

are upregulated in B lymphocytes from patients suffering from CLL. PCP is highly<br />

conserved signaling machinery, which acts as key regulator of cell polarity and migration<br />

throughout evolution. Several players of the PCP pathway, such as Prickle1, Celsr1,<br />

Vangl2, casein kinase 1 (Ck1ε), Dvl2, Dvl3, Fzd3, Fzd7 and Wnt5a, are increased in CLL<br />

cells both on mRNA and protein levels. The expression levels of PCP genes and proteins<br />

often correlate with the aggressiveness of the disease and some of the PCP genes have<br />

prognostic value.<br />

Further, our analysis of the migratory capacity of CLL model cell line Mec1 and human<br />

primary CLL lymphocytes in the chemokine gradient (Transwell Assay) suggests that<br />

PCP pathway is required for migration of leukemic cells. We were able to decrease<br />

CLL lymphocyte migration using (i) Ror1 blocking antibody, (ii) CK1 inhibitor D4476<br />

Analytical Cytometry VII 47

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