Novel evidence that pituitary gonadotropins directly stimulate human leukemic cells-studies of myeloid cell lines and primary patient AML and CML cells
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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
Mariusz Ratajczak, e-mail: firstname.lastname@example.org
Magda Kucia, e-mail: email@example.com
Keywords: leukemia, lymphoma, germ line, FSH, LH
Received: August 25, 2015 Accepted: November 21, 2015 Published: December 20, 2015
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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