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Transcription factors Fli1 and EKLF in the differentiation of megakaryocytic and erythroid progenitor in 5q- syndrome and in Diamond–Blackfan anemia

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Abstract

Friend leukemia virus integration 1 (Fli1) and erythroid Krüppel-like factor (EKLF) participate under experimental conditions in the differentiation of megakaryocytic and erythroid progenitor in cooperation with other transcription factors, cytokines, cytokine receptors, and microRNAs. Defective erythropoiesis with refractory anemia and effective megakaryopoiesis with normal or increased platelet count is typical for 5q- syndrome. We decided to evaluate the roles of EKLF and Fli1 in the pathogenesis of this syndrome and of another ribosomopathy, Diamond–Blackfan anemia (DBA). Fli1 and EKLF mRNA levels were examined in mononuclear blood and bone marrow cells from patients with 5q- syndrome, low-risk MDS patients with normal chromosome 5, DBA patients, and healthy controls. In 5q- syndrome, high Fli1 mRNA levels in the blood and bone marrow mononuclear cells were found. In DBA, Fli1 expression did not differ from the controls. EKLF mRNA level was significantly decreased in the blood and bone marrow of 5q- syndrome and in all DBA patients. We propose that the elevated Fli1 in 5q- syndrome protects megakaryocytic cells from ribosomal stress contrary to erythroid cells and contributes to effective though dysplastic megakaryopoiesis.

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Acknowledgments

This work was supported by the research grant NT/13836-4/2012 from the Ministry of Health of the Czech Republic and by the research grant PRVOUK-P27/LF1/2.

Authors' contributions

RN and OF designed the experiments. OF, MH, MV, AK, HH, and MB performed the experiments with the assistance of RC. RN, OF, MH, AK, and HH analyzed the data. KM and JB provided cytogenetical data. RN, AJ, JC, DP, RC, MS, IH, JV, DS, EK, and LN provided the patient clinical samples and hematological data. RN and OF, with the input of HH, wrote the paper.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. 1st Department of Medicine, Department of Hematology, General University Hospital, U Nemocnice 2, Prague 2, 128 00, Czech Republic

    Radana Neuwirtova

  2. 1st Department of Medicine, Department of Hematology, General University Hospital, Charles University, Prague, Czech Republic

    Radana Neuwirtova, Anna Jonasova & Magda Siskova

  3. Institute of Hematology and Blood Transfusion, Prague, Czech Republic

    Ota Fuchs, Monika Holicka, Martin Vostry, Arnost Kostecka, Hana Hajkova, Jaroslav Cermak, Radek Cmejla, Monika Belickova, Dana Sponerova, Ludmila Novakova & Jana Brezinova

  4. Pediatric Clinic, University Hospital, Olomouc, Czech Republic

    Dagmar Pospisilova

  5. Department of Hematology, Motol University Hospital, Prague, Czech Republic

    Ivana Hochova

  6. Department of Hematology, University Hospital, Olomouc, Czech Republic

    Jana Vondrakova

  7. Department of Hematology, Bata Hospital, Zlin, Czech Republic

    Eva Kadlckova

  8. Center of Oncocytogenetics, General University Hospital, Charles University, Prague, Czech Republic

    Kyra Michalova

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  1. Radana Neuwirtova
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Correspondence to Radana Neuwirtova.

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Neuwirtova, R., Fuchs, O., Holicka, M. et al. Transcription factors Fli1 and EKLF in the differentiation of megakaryocytic and erythroid progenitor in 5q- syndrome and in Diamond–Blackfan anemia. Ann Hematol 92, 11–18 (2013). https://doi.org/10.1007/s00277-012-1568-1

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