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Updated: Aug 8, 2026
Ex vivo Mimicry of Normal and Abnormal Human Hematopoiesis
Published on: April 10, 2012
Effect of IFN-alpha on normal human hematopoiesis: an immunohistochemical and morphometric study on trephine biopsy
J Thiele1, C Wickenhauser, C Neuwirth
1Institute of Pathology, University of Cologne, Germany. J.Thiele@uni-koeln.de
Insights
Interferon-alpha (IFN-alpha) treatment increased megakaryocytes and reticulin fibers in normal human bone marrow. Apoptosis decreased, suggesting IFN-alpha supports steady-state hematopoiesis.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Interferon-alpha (IFN-alpha) is used therapeutically.
- Its effects on normal human bone marrow in vivo require elucidation.
- Previous studies focused on specific disease states or in vitro conditions.
Purpose of the Study:
- To investigate the in vivo effects of low-dose interferon-alpha (IFN-alpha) on normal human bone marrow.
- To assess changes in bone marrow cellularity, fiber content, and specific cell populations.
- To compare in vivo findings with existing in vitro data.
Main Methods:
- Immunomorphometric analysis of trephine bone marrow biopsy specimens.
- Sequential sampling from patients with mycosis fungoides undergoing IFN-alpha therapy.
- Quantification of reticulin fibers, megakaryocytes, macrophages (total and activated), proliferation (PCNA), and apoptosis.
Main Results:
- Significant increase in megakaryocyte count and reticulin fiber density.
- Significant decrease in proliferating cell nuclear antigen (PCNA)+ cells and apoptotic bodies.
- No significant change in total or activated macrophage populations.
- Detected fibrogenetic capacity of IFN-alpha associated with megakaryocyte growth.
Conclusions:
- In vivo IFN-alpha therapy promotes megakaryocyte growth and bone marrow fibrosis.
- Reduced apoptosis suggests a role in maintaining steady-state hematopoiesis.
- Findings contrast with in vitro data and IFN-alpha effects in chronic myelogenous leukemia.
Abstract:
To elucidate the effects of interferon-alpha (IFN-alpha) on normal human bone marrow in vivo, an immunomorphometric study was performed using trephine biopsy specimens without hematopoietic pathology. Samples were derived from patients with mycosis fungoides but no marrow involvement, who were undergoing low-dose IFN-alpha treatment. Parameters included density of reticulin (argyrophilic) fibers, CD61+ megakaryocytes, PGM1+ macrophages, the GSA-I lectin-expressing (activated) macrophage subpopulation, proliferative activity (PCNA staining), and apoptosis. Following IFN-alpha therapy (3 x 3 x 10(6) U/week between 6 and 21 months), morphometric evaluation of sequential bone marrow examinations revealed a significant increase in the number of megakaryocytes and the amount of reticulin fibers. Additionally, there was an overall decrease in PCNA+ cells, accompanied by a reduction in the incidence of apoptotic bodies. On the other hand, total number of macrophages and their activated subfraction remained unchanged. Opposed to in vitro findings, a fibrogenetic capacity of IFN-alpha associated with megakaryocyte growth was detectable. Moreover, contrasting with effects of IFN-alpha treatment in chronic myelogenous leukemia, the incidence of apoptosis was significantly reduced. This feature was assumed to contribute to a maintenance of steady-state hematopoiesis expressed by a nonaltered bone marrow cellularity in our specimens.
