The Leukemia Cell Biology Group

Principal Investigator: Zsuzsanna Hevessy MD, PhD

Members of the group:
Aniko Ujfalusi MD, PhD; László Csáthy MD; Eszter Szánthó MD; Bettina Kárai MD

Technician: Valéria Kiss Sziráki

Leukemias are malignant hematological diseases characterized by the accumulation of pathological myeloid or lymphoid cells. Our group investigates the cell surface and intracellular antigen characteristics of leukemic blasts and cells of premalignant states (PNH and MDS). 1. We have described the presence of blood coagulation factor XIII subunit A in AML M4/M5 blasts and characterized the same phenomenon as leukemia associated immunophenotype (LAIP) in B precursor ALL and acute promyelocytic leukemia as well. Recently, we investigate the prognostic impact of FXIII-A positivity in different leukemias. These studies are carried out in collaboration with the Department of Pediatric Onco-Hematology and the Department of Hematology. Intracellular localization of FXIII-A in blasts is detected by laser scanning microscopy in collaboration with Dr. György Vereb from the Department of Biophysics and Cell Biology. We also study the prognostic role of the amount of residual blasts after chemotherapy (15 days and 33 days) in ALL children. We participate in a multicenter Central-European study (ALL-IC) being the coordinators of the project. Our group has an intense collaboration with the group of Prof. László Muszbek at the Clinical Research Center in Debrecen, where FXIII-A monoclonal antibody was developed and FXIII-A content of leukemic blasts is measured by ELISA. 2. Several types of drug resistance mechanisms have been identified in acute leukemias, including the presence of the multidrug resistance proteins: MDR1 or P-glycoprotein, multidrug resistance-associated protein (MRP1) and breast cancer resistance protein (BCRP) seem to be the most frequent and best-characterized causes of therapy failure. The functional presence of MDR proteins may be a prognostic marker in several types of leukemia. Multicenter studies are carried out in collaboration with the hematologists of the University of Szeged, Pécs and Debrecen and the Solvo Biotechnological Ltd in order to develop and evaluate a standardized multidrug resistance (MDR) functional assay with the separate measurement of the different pump activities and their prognostic value in different leukemias (AML and CLL). 3. In collaboration with the the Department of Hematology and the B-A-Z County Hospital Department of Pediatric Onco-Hematology and the Department of Hematology we perform multicolor flow cytometry analysis and detection of cancer stem cells (CSCs) with the aldehyde dehydrogenase kit (CD34+/CD38-/ALDHhigh+). Meanwhile FXIIIA expression is detected in CSCs and the differentiated population as well. Programmed cell death is also investigated with flow cytometric methods (Annexin V and caspase-3 activity). 4. In collaboration with the cytogenetic laboratory we would like to investigate correlation between cytogenetic aberrations and immunophenotypic profiles of acute leukemias (ALL, AML) and other hematological malignancies. The Leukemia Cell Biology Group utilizes mostly flow cytometric, Western-blot and ELISA techniques, G-banded chromosome analysis, FISH, multicolor FISH, but we have access to confocal laser scanning microscopic capability as well.

Representative publications:

Csáthy L, Kappelmayer J, Szegedi I, Kajtár B, Kiss C Hevessy Z. Classical and atypical Bedekovics J, Rejtő L, Telek B, Kiss A, Hevessy Zs, Újfalusi A, Méhes G. Identification of NPMc+ acute myeloid leukemia in bone marrow smears. Appl Immunohistochem Mol Morphol 2013, 21(1): 73-78

Simon Á, Bagoly Zs, Hevessy Zs, Csáthy L, Katona É, Vereb Gy, Ujfalusi A, Szerafin L, Muszbek L, Kappelmayer J. Expression of coagulation factor XIII subunit A in acute promyelocytic leukemia. Cytometry B (Clinical Cytometry) 2012, 82B: 209-216

Hevessy Zs, Hudak R, Kiss-Sziraki V, Antal-Szalmas P, Udvardy M, Rejtő L,  Szerafin L, Kappelmayer J. Laboratory evaluation of a flow cytometric BCR-ABL immunobead assay. Clin Chem Lab Med 2012, 50 (4): 689-692
Csáthy L, Kappelmayer J, Szegedi I, Kajtár B, Kiss C Hevessy Z. Classical and atypical neuroblastoma - case reports. Cytometry B (Clinical Cytometry) 2011, 80B: 134-136
Kiss F, Buslig J, Szegedi I, Scholtz B, Kappelmayer J, Kiss C. Early relapse after rituximab chemoimmunotherapy. Pediatr Blood Cancer 2008, 50: 372-5

Kiss F, Simon A, Csathy L, Hevessy Z, Katona E, Kiss C, Kappelmayer J. A coagulation factor becomes useful in the study of acute leukemias: studies with blood coagulation factor XIII. Cytometry A 2008, 73: 194-201

Kiss F, Hevessy Z, Veszprémi A, Katona É, Vereb G, Kiss C, Muszbek L, Kappelmayer J. Leukemic lymphoblasts: a novel expression site for coagulation factor XIII subunit A. Thromb Haemost 2006,96: 176-182

Hevessy Z, Nagy B Jr, Kiss F, Kiss A, Kappelmayer J. Mean fluorescence intensity rate is a useful marker in the detection of paroxysmal nocturnal hemoglobinuria clones. Clin Chem Lab Med 2005, 43: 919-923

Kappelmayer J, Simon A, Katona E, Szanto A, Nagy L, Kiss A, Kiss C, Muszbek L. Coagulation factor XIII-A. A flow cytometric intracellular marker in the classification of acute myeloid leukemias. Thromb Haemost 2005, 94: 454-9

Kappelmayer J, Simon Á, Kiss F, Hevessy Z. Progress in defining multidrug resistance in leukemia. Exp Rev Mol Diagnos 2004, 2: 209-217

Karászi E, Jakab K, Homolya L, Szakács G, Holló Z, Telek B, Kiss A, Rejtő L, Nahajevszky S, Sarkadi B, Kappelmayer J. Calcein assay for multidrug resistance reliably predicts therapy response and survival rate in acute myeloid leukemia. Br J Haematol 2001, 112: 308-14
Kappelmayer J, Gratama JW, Karászi E, Menéndez P, Ciudad J, Rivas R, Orfao A. Flow cytometric detection of intracellular myeloperoxidase, CD3 and CD79a. Interaction between monoclonal antibody clones, fluorochromes and sample preparation protocols. J Immunol Methods 2000, 242: 53-65