Initial experience with L-leucine therapy in myelodysplastic syndromes with associated chromosome 5q deletion.

摘要

In murine and zebrafish preclinical models of Diamond-Blackfan anemia (DBA), supplementation with the essential amino acid L-leucine ameliorates defective erythropoiesis and alleviates anemia, probably via upregulation of the mammalian target of rapamycin signaling pathway.1"3 In addition, at least a single European patient with DBA experienced improved hemoglobin levels during L-leucine supplementation.4 Because dysregulated ribosome biogenesis similar to that underlying DBA is present in cells from patients with myelodysplastic syndromes (MDSs) associated with deletion of chromosome 5q, it has been proposed that L-leucine might also improve MDS-associated anemia, especially in patients with the so-called 5q- syndrome, a lower-risk form of MDS associated with haploinsufficiency of ribosomal component ribosomal protein S14.1'5 To date, no clinical experience with L-leucine in MDS has been reported, although the low cost, widespread availability, and excellent tolerability of this dietary supplement suggest that clinical trials should be undertaken.