Enhanced hematopoietic growth factor production in an experimental myeloproliferative syndrome

Abstract

The murine myeloproliferative syndrome induced by the myeloproliferative sarcoma virus (MPSV) has numerous similarities to human primary myelofibrosis. We have shown that medium conditioned by spleen cells of MPSV-infected mice has the capacity to support the growth of primitive blast cell colonies. The detection of this activity associated with MPSV infection stimulated us to characterize the hematopoietins responsible for this activity. Northern blot analysis showed a large increase, or induction, of interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage- CSF (CSF-1), and granulocyte-CSF (G-CSF) transcripts in the hematopoietic organs of MPSV-infected mice; however, no IL-3 transcript could be detected in either MPSV-infected or normal mice. Significant levels of IL-1 alpha, IL-6, G-CSF, and CSF-1 bioactivities were found in the serum of MPSV-infected mice, but not in controls. Additionally, analysis of medium conditioned by spleen cells of MPSV-infected mice showed the presence of tumor necrosis factor alpha bioactivity. The increased production of cytokines that are able to stimulate pluripotent hematopoietic stem cells corroborates the hypothesis of a possible involvement of hematopoietic growth factors in the development of some myeloproliferative disorders.

Pathogenesis of Idiopathic Myelofibrosis: Present Status and Future Directions

“…Breakpoints of several such abnormalities require to be isolated, and cloned, to identify molecular details such as the repetitive sequences that have been associated with interstitial deletions of the long arm of chromosome 5 (Nagarajan et al, 1990). The development of animal models, such as the MPSV-induced myeloproliferative syndrome (Le Bousse-Kerdiles et al, 1992), which closely mimics human idiopathic myelofibrosis, have suggested a pathogenetic role for several additional cytokines. including IL-la, IG6 and G-CSF.…”

Interleukin‐10 inhibits autonomous myelopoiesis in patients with myelofibrosis

“…This question remains open in MF, but some in vivo data suggest a significant contribution of aberrant cytokine signaling in the expansion of the malignant clone. Enhanced hematopoietic growth factor production has been found in an experimental myeloproliferative syndrome that is induced by the myeloproliferative sarcoma virus (MPSV) and has numerous similarities to human MF . Furthermore, a large number of cytokines have also been shown to be upregulated in patients with MF .…”

Durable Responses to Thalidomide-Based Drug Therapy for Myelofibrosis With Myeloid Metaplasia

“…Remember that MMM is a clonal stem cell disease that is accompanied by a cytokine-mediated bone marrow stromal reaction (collagen fibrosis, osteosclerosis, angiogenesis) and ineffective hematopoiesis. 1 Both angiogenesis 12 and tumor necrosis factor α (TNF-α) have been implicated in the pathogenesis of MMM, and the latter may be particularly detrimental to effective erythropoiesis in both MMM 28 and MDS. 29 Therefore, it is tempting to attribute the observed effects of thalidomide to its antiangiogenic and anti-TNF-α properties.…”