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; Magda Kucia

doi:10.18632/oncotarget.6698

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

Oncotarget. 2016 Jan 19;7(3):3033-46. doi: 10.18632/oncotarget.6698.

Authors

Affiliations

¹ Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, KY, USA.
² Pomeranian Medical University, Szczecin, Poland.
³ Department of Hematology, University of Alberta, Edmonton, Canada.
⁴ Transfusion Medicine, Medical Faculty Carl Gustav Carus - Technische Universtität Dresden, German Red Cross Blood Donation Service North East, Dresden, Germany.
⁵ Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland.
⁶ Department of Hematology, Medical University of Bialystok, Bialystok, Poland.
⁷ Department of Regenerative Medicine Medical University of Warsaw, Warsaw, Poland.

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.

Keywords: FSH; LH; germ line; leukemia; lymphoma.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cell Adhesion / physiology
Cell Line, Tumor
Cell Movement / physiology
Cell Proliferation / physiology
Follicle Stimulating Hormone / pharmacology*
Gonadotropins, Pituitary / metabolism*
Humans
Jurkat Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
Leukemia, Myeloid, Acute / metabolism*
Luteinizing Hormone / pharmacology*
Mitogen-Activated Protein Kinases / metabolism
Myeloid Cells / metabolism
Phosphorylation
Proto-Oncogene Proteins c-akt / metabolism
Receptors, Pituitary Hormone / metabolism*
Signal Transduction

Substances

Gonadotropins, Pituitary
Receptors, Pituitary Hormone
Luteinizing Hormone
Follicle Stimulating Hormone
Proto-Oncogene Proteins c-akt
Mitogen-Activated Protein Kinases

Abstract

Publication types

MeSH terms

Substances

Grants and funding