Effect of thrombopoietin on proliferation of blasts from patients with myelodysplastic syndromes

Thrombopoietin (TPO), a major cytokine involved in megakaryocytopoiesis/thr ombopoiesis, may be effective for treatment of the thrombocytopenia associa ted with myelodysplastic syndromes (MDS). However, it has been unclear whet her TPO stimulates proliferation of MDS blasts, as observed in de novo acut e myeloid leukemia, This study examined this concern. When marrow cells fro m 37 MDS cases were cultured with or without recombinant human PEGylated TP O, TPO increased the blast number (stimulation index greater than or equal to 1.5) in 9 of 16 high-risk MDS cases (refractory anemia with excess blast s [RAEB] and RAEB in transformation) and 4 of 10 cases with MDS transformed to acute leukemia (MDS-AL), but none of 11 cases with low-risk MDS (RA and RA with ringed sideroblasts), When the cell cycle of cultured cells was de termined by three-color now cytometry, TPO activated the cell cycle of MDS cells (causing a decrease in G(0)-phase cells) in most of the cases whose b last number increased in response to TPO, Reverse transcriptase-polymerase chain reaction analysis detected TPO receptor messenger RNA in purified bla sts from all six cases examined, irrespective of the response of their blas ts to TPO in culture. Analysis of the patients' characteristics identified a high-serum lactate dehydrogenase (LDH) value as being associated with bla st proliferation in high-risk MDS cases (p = 0.0036), We conclude that TPO stimulates in vitro proliferation of blasts from a fraction of MDS patients . High-risk MDS patients, especially those who have a high-serum LDH value, and MDS-AL patients should be monitored with particular care in clinical t rials of TPO for MDS.