Oncotarget

Research Papers:

Novel evidence that pituitary gonadotropins directly stimulate human leukemic cells-studies of myeloid cell lines and primary patient AML and CML cells

Ahmed Abdelbaset-Ismail, Sylwia Borkowska, Anna Janowska-Wieczorek, Torsten Tonn, Cesar Rodriguez, Marcin Moniuszko, Lukasz Bolkun, Janusz Koloczko, Andrzej Eljaszewicz, Janina Ratajczak, Mariusz Z. Ratajczak _ and Magda Kucia

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Oncotarget. 2016; 7:3033-3046. https://doi.org/10.18632/oncotarget.6698

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Abstract

Ahmed Abdelbaset-Ismail1, Sylwia Borkowska2, Anna Janowska-Wieczorek3, Torsten Tonn4, Cesar Rodriguez1, Marcin Moniuszko5, Lukasz Bolkun7, Janusz Koloczko7, Andrzej Eljaszewicz5, Janina Ratajczak1, Mariusz Z. Ratajczak1,6, Magda Kucia1,6

1Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, KY, USA

2Pomeranian Medical University, Szczecin, Poland

3Department of Hematology, University of Alberta, Edmonton, Canada

4Transfusion Medicine, Medical Faculty Carl Gustav Carus - Technische Universtität Dresden, German Red Cross Blood Donation Service North East, Dresden, Germany

5Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland

6Department of Regenerative Medicine Medical University of Warsaw, Warsaw, Poland

7Department of Hematology, Medical University of Bialystok, Bialystok, Poland

Correspondence to:

Mariusz Ratajczak, e-mail: mzrata01@louisville.edu

Magda Kucia, e-mail: mjkuci01@louisville.edu

Keywords: leukemia, lymphoma, germ line, FSH, LH

Received: August 25, 2015     Accepted: November 21, 2015     Published: December 20, 2015

ABSTRACT

We recently reported that normal hematopoietic stem cells express functional pituitary sex hormone (SexH) receptors. Here we report for the first time that pituitary-secreted gonadotrophins stimulate migration, adhesion, and proliferation of several human myeloid and lymphoid leukemia cell lines. Similar effects were observed after stimulation of human leukemic cell lines by gonadal SexHs. This effect seems to be direct, as the SexH receptors expressed by leukemic cells responded to stimulation by phosphorylation of MAPKp42/44 and AKTser473. Furthermore, in parallel studies we confirmed that human primary patient-derived AML and CML blasts also express several functional SexH receptors. These results shed more light on the potential role of SexHs in leukemogenesis and, in addition, provide further evidence suggesting a developmental link between hematopoiesis and the germline.


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