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Diamond-Blackfan syndrome. I. Erythropoiesis in prednisone responsive and resistant disease
Insights
Prednisone effectively treated Diamond-Blackfan syndrome in one infant by improving erythroid progenitor cells. However, the other infant showed no improvement, indicating steroid unresponsiveness in their anemia.
Area of Science:
- Hematology
- Pediatric Hematology
- Stem Cell Biology
Background:
- Diamond-Blackfan syndrome is a rare congenital red blood cell anemia.
- Erythroid progenitor cells, like CFU-E and BFU-E, are crucial for red blood cell production.
- The role of prednisone in treating Diamond-Blackfan syndrome can vary between patients.
Purpose of the Study:
- To investigate the in vitro proliferative characteristics of erythroid progenitors in infants with Diamond-Blackfan syndrome.
- To assess the impact of prednisone treatment on these progenitors.
- To differentiate between steroid-responsive and steroid-unresponsive cases.
Main Methods:
- Studied colony forming unit-erythroid (CFU-E) and burst forming unit-erythroid (BFU-E) in vitro.
- Utilized erythropoietin dose-response studies.
- Employed unit gravity sedimentation (STA-PUT) to isolate stem cell-rich marrow fractions.
Main Results:
- Patient 1 showed improved anemia with prednisone, exhibiting increased CFU-E and BFU-E in dose-response studies and normalized colony numbers after stem cell enrichment during treatment.
- Patient 2 was unresponsive to prednisone, with severely reduced CFU-E and BFU-E both before and during therapy, even in enriched fractions.
- Prednisone enhanced progenitor differentiation in Patient 1 but did not affect the erythropoietic failure in Patient 2.
Conclusions:
- Diamond-Blackfan syndrome can present with varying responses to prednisone.
- Patient 1's progenitors required prednisone for normal differentiation, suggesting a conditional dependence.
- Patient 2's erythropoietic failure was independent of prednisone, highlighting a non-response mechanism.
Abstract:
We studied the in vitro proliferative characteristics of marrow erythroid progenitors, colony forming unit-erythroid (CFU-E) and burst forming unit-erythroid (BFU-E), in two infants with Diamond-Blackfan syndrome before and during prednisone treatment. Patient 1, had a brisk erythropoietic response to prednisone and the anemia improved; Patient 2 was steroid-unresponsive. Marrow from Patient 1 yielded linear increases in numbers of colonies in erythropoietin dose-response studies, and the magnitude of response was much greater while on prednisone compared to pretreatment. Cultures of stem cell rich fractions of marrow from Patient 1 separated by unit gravity sedimentation (STA-PUT) revealed moderately reduced CFU-E and BFU-E numbers before prednisone, but normal colony numbers during treatment. Patient 2 differed because CFU-E and BFU-E were almost absent at all erythropoietin doses before and during therapy. Even stem cell rich marrow fraction initially yielded very low colony numbers which did not increase significantly while on prednisone. These findings suggest that in Patient 1 there were adequate numbers of progenitors that were able to differentiate normally only in the presence of prednisone. In Patient 2 the erythropoietic failure in vivo and in vitro was unaffected by prednisone.