Gender dimorphism in the myeloid differentiation of bone marrow precursor cells in a murine host bearing a T cell lymphoma

Abstract

Little information is available regarding the existence of gender dimorphism of tumor growth for most types of tumors. In a previous report we have demonstrated the existence of gender dimorphism in the growth of a murine T cell lymphoma, designated as Dalton's lymphoma (DL); moreover, tumor-associated macrophages (TAM) were found to play a central role in the manifestation of gender dimorphism observed in the growth of this T cell lymphoma. In view of these observations, the present investigation was undertaken to study if gender dimorphism in the growth of a T cell tumor also could be associated with a gender-dependent differential myelopoiesis of bone marrow cells. We have demonstrated the existence of a gender dimorphism in the proliferation, apoptosis and myeloid differentiation of bone marrow cells obtained from male and female tumor-bearing hosts. Androgen and estrogen were found to alter directly the growth properties of bone marrow cells, as also determined by the use of receptor antagonists of these hormones, flutamide and tamoxifen. Bone marrow cells of male and female tumor-bearing hosts also showed a differential expression of the cell cycle and apoptosis regulatory protein p53 and macrophage-colony stimulating factor (M-CSF) genes. Bone marrow cells of male tumor-bearing hosts showed a predominant differentiation in the macrophage lineage whereas those of female tumor-bearing mice were in the granulocyte lineage. Bone marrow-derived macrophages (BMDM) from male and female tumor-bearing mice also showed the existence of gender dimorphism with respect to their differentiation and activation. These observations are of clinical significance with respect to understanding of the host–tumor relationship at the level of gender dimorphism of myelopoiesis.