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Tumor necrosis factor-alpha suppresses hematopoiesis in children with myelodysplasia
S S Winter1, G A Hanissian, T O Harville
1Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
Abstract:
The term myelodysplasia (MDS) refers to a group of bone marrow failure syndromes which are relatively rare in childhood. The pathogenesis of MDS is unknown, but a variety of chromosomal, molecular, and cytochemical abnormalities have been reported. We describe a 4-month-old female with MDS who presented with severe neutropenia and refractory anemia with excess blasts (RAEB). Bone marrow progenitor cell assays showed decreased erythroid and myeloid colony formation as compared to normal marrow, and the patient's serum further diminished colony formation of both her own and control marrow. These observations suggested the presence of a soluble factor inhibitory to hematopoiesis. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of total RNA derived from the patient's bone marrow mononuclear cells revealed highly elevated tumor necrosis factor-alpha (TNF-alpha) mRNA levels. Using a similar RT-PCR profile, TNF-alpha mRNA levels were found to be elevated in two other children with myelodysplasia. We conclude that TNF-alpha is produced in large amounts by bone marrow mononuclear cells of children with MDS, and we hypothesize that TNF-alpha plays an important role in the pathophysiology of the ineffective hematopoiesis observed in MDS.
Insights
Pediatric myelodysplasia (MDS) involves bone marrow failure. This study found elevated tumor necrosis factor-alpha (TNF-alpha) in children with MDS, suggesting its role in the disease.
Area of Science:
- Pediatric Hematology
- Oncology
- Immunology
Background:
- Myelodysplasia (MDS) comprises rare childhood bone marrow failure syndromes.
- The exact cause of MDS remains unknown, though various abnormalities are documented.
Observation:
- A 4-month-old female with MDS presented with severe neutropenia and refractory anemia with excess blasts (RAEB).
- Bone marrow assays revealed reduced erythroid and myeloid colony formation.
- Patient serum inhibited hematopoiesis in her own and control marrow, indicating a soluble inhibitory factor.
Findings:
- Reverse transcriptase-polymerase chain reaction (RT-PCR) detected significantly elevated tumor necrosis factor-alpha (TNF-alpha) mRNA in the patient's bone marrow cells.
- Elevated TNF-alpha mRNA levels were also observed in two other pediatric MDS cases.
Implications:
- This research suggests that TNF-alpha is abundantly produced by bone marrow cells in pediatric MDS.
- The findings hypothesize a significant role for TNF-alpha in the ineffective hematopoiesis characteristic of MDS.