Laboratory of Haematooncology and Stem Cells

Prof. MUDr. Tomáš Stopka, Ph.D. — Project head

1st Faculty of Medicine of the Charles University

About us

The laboratory focuses on basic research in the field of hematooncology, specifically Myelodysplastic Syndromes, Acute Myeloid Leukemia, but also in the field of lymphoproliferations including Multiple Myeloma.

Specifically, the laboratory investigates issues of therapeutic resistance of cancer stem cells and their clonal selection, as well as the specific mechanisms by which tumor bypasses the antitumor effect and how gene expression in resistant cells is specifically reprogrammed to specific therapeutic agents. The lab utilizes OMICs technology in addition to molecular biology approaches, and in addition to cellular models, creates personalized mouse models of tumorigenesis, so-called 'patient-derived xenografts' (PDX), for the investigation of new therapeutic agents and approaches.

We aim:

Understand the mechanisms of resistance in epigenetic therapy with hypomethylating agents in Myelodysplastic Syndrome.
To uncover novel mechanisms of clonal selection of Plasmacytoma cells in the presence of proteasome inhibitors.
To understand the epigenetic mechanisms of normal and tumor biology in early stem cell differentiation.

Further information can be found at www.phenogenomics.cz or at Hematologylaboratories.

News

Milan Jakubek became the new Head of Department of the 1st Faculty of Medicine of Charles University at BIOCEV

Hematopoietic stem cells use chromatin-remodeling factors for specific processes: the story of Smarca5.

Scientists from the 1st Faculty of Medicine of Charles University and BIOCEV received six grants from the GAČR!

The research centre the faculty deserved

Will Czech scientists change the paradigm of treatment of "high-risk" myelodysplastic syndrome?

Minister Helena Langšádlová visited BIOCEV

Czech physicians and researchers to prolong the lives of people with leukaemia

Protein oxidation: an added layer of regulation during blood stem cell development

Researchers from BIOCEV have demonstrated that the proper development of T cells prevents autoimmune disorders

Publications

2024

Turkova T, Kokavec J, Zikmund T, Dibus N, Pimkova K, Nemec D, Holeckova M, Ruskova L, Sedlacek R, Cermak L, Stopka T. Differential requirements for Smarca5 expression during hematopoietic stem cell commitment. Commun Biol. 2024 Feb 29;7(1):244. doi: 10.1038/s42003-024-05917-z. (IF 5.9)

Stoler-Barak L, Schmiedel D, Sarusi-Portuguez A, Rogel A, Blecher-Gonen R, Haimon Z, Stopka T, Shulman Z. SMARCA5-mediated chromatin remodeling is required for germinal center formation. J Exp Med. 2024 Nov 4;221(11):e20240433. doi: 10.1084/jem.20240433. (IF 12.6)

Jonasova A, Sotakova S, Belohlavkova P, Minarik L, Stopka T, Jonas JJ, Aghova T, Zemanova Z. Experience with luspatercept therapy in patients with transfusion-dependent low-risk myelodysplastic syndromes in real-world clinical practice: exploring the positive effect of combination with erythropoietin alfa. Front Oncol. 2024 Oct 2;14:1398331. doi: 10.3389/fonc.2024.1398331. (IF 3.5)

2023

Vajrychova M, Salovska B, Pimkova K, Fabrik I, Hodny Z. SILAC-IodoTMT for Assessment of the Cellular Proteome and Its Redox Status. Methods Mol Biol. 2023;2603:259-268. doi: 10.1007/978-1-0716-2863-8_21.

Kuzelova A, Dupacova N, Antosova B, Sunny SS, Kozmik Z Jr., Paces J, Skoultchi AI, Stopka T, Kozmik Z. Chromatin Remodeling Enzyme Snf2h Is Essential for Retinal Cell Proliferation and Photoreceptor Maintenance. Cells. 2023; 12(7):1035. https://doi.org/10.3390/cells12071035 (IF 7.67)

2022

Minařík L, Pimková K, Kokavec J, Schaffartziková A, Vellieux F, Kulvait V, Daumová L, Dusilková N, Jonášová A, Vargová KS, Králová Viziová P, Sedláček R, Zemanová Z, Stopka T. Analysis of 5-Azacytidine Resistance Models Reveals a Set of Targetable Pathways. Cells. 2022 Jan 11;11(2):223. doi: 10.3390/cells11020223. (IF 6.6)

Thakur S, Cahais V, Turkova T, Zikmund T, Renard C, Stopka T, Korenjak M, Zavadil J. Chromatin Remodeler Smarca5 Is Required for Cancer-Related Processes of Primary Cell Fitness and Immortalization. Cells. 2022 Feb 25;11(5):808. doi: 10.3390/cells11050808. (IF 6.6)

Krsmanovic P, Mocikova H, Chramostova K, Klanova M, Trnkova M, Pesta M, Laslo P, Pytlik R, Stopka T, Trneny M, Pospisil V. Circulating microRNAs in Cerebrospinal Fluid and Plasma: Sensitive Tool for Detection of Secondary CNS Involvement, Monitoring of Therapy and Prediction of CNS Relapse in Aggressive B-NHL Lymphomas. Cancers. 2022; 14(9):2305. https://doi.org/10.3390/cancers14092305 (IF 6.6)

Bašová P, Paszeková H, Minařík L, Dluhošová M, Burda P, Stopka T. Combined Approach to Leukemic Differentiation Using Transcription Factor PU.1-Enhancing Agents. Int J Mol Sci. 2022 Jun 16;23(12):6729. doi: 10.3390/ijms23126729. (IF 5.9)

Stopka T, Minařík L, Dusilková N, Pešta M, Kulvait V, Špaček M, Zemanová Z, Kalousová M, Jonášová A. G-CSF plus azacitidine versus azacitidine alone for patients with high-risk myelodysplastic syndrome: academic, open label, randomized trial. Blood Cancer J. 2022 Jul 7;12(7):105. doi: 10.1038/s41408-022-00698-2. (IF 11.98)

Pimkova K, Jassinskaja M, Munita R, Ciesla M, Guzzi N, Cao Thi Ngoc P, Vajrychova M, Johansson E, Bellodi C, Hansson J. Quantitative analysis of redox proteome reveals oxidation-sensitive protein thiols acting in fundamental processes of developmental hematopoiesis. Redox Biology. Volume 53, July 2022, 102343. ISSN 2213-2317. https://doi.org/10.1016/j.redox.2022.102343. (IF 11.79)

Salovska B, Kondelova A, Pimkova K, Liblova Z, Pribyl M, Fabrik I, Bartek J, Vajrychova M, Hodny Z. Peroxiredoxin 6 protects irradiated cells from oxidative stress and shapes their senescence-associated cytokine landscape. Redox Biol. 2022 Feb;49:102212. doi: 10.1016/j.redox.2021.102212. (IF 11.79)

2020

Zikmund T, Paszekova H, Kokavec J, Kerbs P, Thakur S, Turkova T, Tauchmanova P, Greif PA, Stopka T. Loss of ISWI ATPase SMARCA5 (SNF2H) in Acute Myeloid Leukemia Cells Inhibits Proliferation and Chromatid Cohesion. Int J Mol Sci. 2020;21(6):E2073. Published 2020 Mar 18. doi:10.3390/ijms21062073. (IF 4.183)

Zhang C, Chen Z, Yin Q, Fu X, Li Y, Stopka T, Skoultchi A, Zhang Y. The chromatin remodeler Snf2h is essential for oocyte meiotic cell cycle progression. Genes Dev. 2020;34(3-4):166–178. doi:10.1101/gad.331157.119. (IF 8.998)

Pribyl M, Hubackova S, Moudra A, Vancurova M, Polackova H, Stopka T, Jonasova A, Bokorova R, Fuchs O, Stritesky J, Salovska B, Bartek J, Hodny Z. Aberrantly elevated suprabasin in the bone marrow as a candidate biomarker of advanced disease state in myelodysplastic syndromes. Mol Oncol. 2020 Oct;14(10):2403-2419. doi: 10.1002/1878-0261.12768. (IF 6.574)

Minarik L, Vargova K, Dusilkova N, Kulvait V, Jonasova A, Kodet O, Stopka T. Hereditary Haemorrhagic Telangiectasia (HHT) Marked by ACVRL1C1120T Variant Displays Hypopigmented Naevi and Frequent Bleeding Episodes if CYP2C9 Co-Mutated: Clinical Notes & Rationale of Patient Registry. Folia Biol (Praha). 2020;66(1):1-6. (IF 1.073)

2019

Zikmund T, Kokavec J, Turkova T, Savvulidi F, Paszekova H, Vodenkova S,
Sedlacek R, Skoultchi AI, Stopka T. ISWI ATPase Smarca5 Regulates Differentiation
of Thymocytes Undergoing β-Selection. J Immunol. 2019 Jun 15;202(12):3434-3446.
doi: 10.4049/jimmunol.1801684.

Skalicka P, Dudakova L, Palos M, Huna LJ, Evans CJ, Mahelkova G, Meliska M, Stopka T, Tuft S, Liskova P. Paraproteinemic keratopathy associated with monoclonal gammopathy of undetermined significance (MGUS): clinical findings in twelve patients including recurrence after keratoplasty. Acta Ophthalmol. 2019 May 2. doi: 10.1111/aos.14123. (IF 3.032)

Minarik L, Zemanova Z, Kulvait V, Dluhosova M, Jonasova A and Stopka T. Azacitidine Switch to Lenalidomide Eradicated the TP53/ CDKN2A Co-Mutated Clone and Induced Long-Term Erythroid Response in Del(5q) MDS. Ann Hematol Oncol. 2019; 6(1): 0000. (IF 2.219)

Stopka T, Minarik L, Kulvait V, Pesta M, Schaffartzikova A, Kislik G, Dusilkova N, Zemanova Z, Jonasova A. Randomizovaná otevřená akademická studie: srovnání standardního podání azacytidinu oproti azacytidinu s preinkubací G-CSF u myelodysplastického syndromu vyššího rizika – interim analýza. Myelodysplastic Syndrome NEWS. Ročník 7 / číslo 2 / listopad 2019.

2018

Srutova K, Curik N, Burda P, Savvulidi F, Silvestri G, Trotta R, Klamova H, Pecherkova P, Sovova Z, Koblihova J, Stopka T, Perrotti D, Polakova KM. BCR-ABL1 mediated miR-150 downregulation through MYC contributed to myeloid differentiation block and drug resistance in chronic myeloid leukemia. Haematologica. 2018 Dec;103(12):2016-2025. doi: 10.3324/haematol.2018.193086. (IF 9.09)

Jonasova A, Neuwirtova R, Polackova H, Siskova M, Stopka T, Cmunt E, Belickova M, Moudra A, Minarik L, Fuchs O, Michalova K, Zemanova Z. Lenalidomide treatment in lower risk myelodysplastic syndromes-The experience of a Czech hematology center. (Positive effect of erythropoietin ± prednisone addition to lenalidomide in refractory or relapsed patients). Leuk Res. 2018 Jun;69:12-17. doi:10.1016/j.leukres.2018.03.015. (IF 2.319)

2017

Kokavec J, Zikmund T, Savvulidi F, Kulvait V, Edelmann W, Skoultchi AI, Stopka T. The ISWI ATPase Smarca5 (Snf2h) Is Required for Proliferation and Differentiation of Hematopoietic Stem and Progenitor Cells. Stem Cells. 2017 Jun;35(6):1614-1623. doi: 10.1002/stem.2604. (IF: 5.599)

Huskova H, Ardin M, Weninger A, Vargova K, Barrin S, Villar S, Olivier M, Stopka T, Herceg Z, Hollstein M, Zavadil J, Korenjak M. Modeling cancer driver events in vitro using barrier bypass-clonal expansion assays and massively parallel sequencing. Oncogene. 2017 Jul 10. doi: 10.1038/onc.2017.215. (IF: 7.519)

Vargova K, Pesta M, Obrtlíkova P, Dusilkova N, Minarik L, Vargova J, Berkova A, Zemanova Z, Michalova K, Spacek M, Trneny M and Stopka T. MiR-155/miR-150 network regulates progression through the disease phases of chronic lymphocytic leukemia. Blood Cancer J. 2017 Jul 21;7(7):e585. doi: 10.1038/bcj.2017.63. (IF: 6.126)

Polgarova K, Vargova K, Kulvait V, Dusilkova N, Minarik L, Zemanova Z, Pesta M, Jonasova A, Stopka T. Somatic mutation dynamics in MDS patients treated with azacitidine indicate clonal selection in patients-responders. Oncotarget. 2017 Dec 6;8(67):111966-111978. doi: 10.18632/oncotarget.22957. (IF 5.168)

Dusílková N, Bašová P, Polívka J, Kodet O, Kulvait V, Pešta M, Trněný M, Stopka T. Plasma miR-155, miR-203, and miR-205 are Biomarkers for Monitoring of Primary Cutaneous T-Cell Lymphomas. Int J Mol Sci. 2017 Oct 15;18(10). pii:E2136. doi: 10.3390/ijms18102136. (IF 3.226)

Bašová P, Pešta M, Sochor M, Stopka T. Prediction Potential of Serum miR-155 and miR-24 for Relapsing Early Breast Cancer. Int J Mol Sci. 2017 Oct 10;18(10). pii: E2116. doi: 10.3390/ijms18102116. (IF 3.226)

2016

He S, Limi S, McGreal RS, Xie Q, Brennan LA, Kantorow WL, Kokavec J, Majumdar R, Hou H Jr, Edelmann W, Liu W, Ashery-Padan R, Zavadil J, Kantorow M, Skoultchi AI, Stopka T, Cvekl A. Chromatin remodeling enzyme Snf2h regulates embryonic lens differentiation and denucleation. Development. 2016 Jun 1;143(11):1937-47. doi: 10.1242/dev.135285..

DN Papageorgiou, E Karkoulia, A Amaral-Psarris, P Burda, K Kolodziej, JA Demmers, J Bungert, T Stopka, J Strouboulis. Distinct and overlapping DNMT1 interactions with multiple transcription factors in erythroid cells: evidence for co-repressor functions. Biochim Biophys Acta. 2016 Dec;1859(12):1515-1526. doi: 10.1016/j.bbagrm.2016.09.007.

P Burda, J. Vargova, N Curik, C Salek, G Papadopoulos, J Strouboulis and T. Stopka. GATA-1 inhibits PU.1 gene via DNA and histone H3K9 Methylation of its Distal Enhancer in Erythroleukemia. PLoS One, 2016 Mar 24;11(3):e0152234

J. Vargova, K. Vargova, N.Dusilkova, V. Kulvait, V. Pospisil, J. Zavadil, M. Trneny, P. Klener, and T. Stopka. Differential Expression, Localization and Activity of MARCKS between Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia. Blood Cancer J. 2016 Sep 23;6(9):e475. (IF: 6.126)

2014

Dluhosova M, Curik N, Vargova J, Jonasova A, Zikmund T, Stopka T. Epigenetic control of SPI1 gene by CTCF and ISWI ATPase SMARCA5. PLoS One. 2014 Feb 3;9(2):e87448. doi: 10.1371/journal.pone.0087448. eCollection 2014

Dluhosova M, Curik N, Vargova J, Jonasova A, Zikmund T,Stopka T. Epigenetic control of SPI1 gene by CTCF and ISWI ATPase SMARCA5. PLoS One. 2014 Feb 3;9(2):e87448.

Alvarez-Saavedra M, De Repentigny Y, Lagali PS, Raghu Ram EV, Yan K, Hashem E, Ivanochko D, Huh MS, Yang D, Mears AJ, Todd MA, Corcoran CP, Bassett EA, Tokarew NJ, Kokavec J, Majumder R, Ioshikhes I, Wallace VA, Kothary R, Meshorer E, Stopka T, Skoultchi AI, Picketts DJ. Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation. Nat Commun. 2014 Jun 20;5:4181 (IF:11.470)

2013

Basova P, Pospisil V, Savvulidi F, Burda P, Vargova K, Stanek L, Dluhosova M, Kuzmova E, Jonasova A, Steidl U, Laslo P, Stopka T.: Aggressive acute myeloid leukemia in PU.1/p53 double-mutant mice. Oncogene. 2013 Oct 14.
doi: 10.1038/onc.2013.414

Machova Polakova K, Koblihova J, Stopka T.: Role of epigenetics in chronic myeloid leukemia. Curr Hematol Malig Rep. 2013 Mar;8(1):28-36.

doi: 10.1007/s11899-012-0152-z

Machova Polakova K, Koblihova J, Stopka T. Role of epigenetics in chronic myeloid leukemia. Curr Hematol Malig Rep. 2013 Mar;8(1):28-36. doi: 10.1007/s11899-012-0152-z. (IF: 2.3)