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

Shan Shun Luo, Kiyoyuki Ogata, Norio Yokose, Takashi Kato, Dan Kazuo

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Thrombopoietin (TPO), a major cytokine involved in megakaryocytopoiesis/thrombopoiesis, may be effective for treatment of the thrombocytopenia associated with myelodysplastic syndromes (MDS). However, it has been unclear whether TPO stimulates proliferation of MDS blasts, as observed in de novo acute myeloid leukemia. This study examined this concern. When marrow cells from 37 MDS cases were cultured with or without recombinant human PEGylated TPO, TPO increased the blast number (stimulation index ≥1.5) in 9 of 16 high-risk MDS cases (refractory anemia with excess blasts [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 determined by three-color flow cytometry, TPO activated the cell cycle of MDS cells (causing a decrease in Go-phase cells) in most of the cases whose blast number increased in response to TPO. Reverse transcriptase-polymerase chain reaction analysis detected TPO receptor messenger RNA in purified blasts from all six cases examined, irrespective of the response of their blasts to TPO in culture. Analysis of the patients' characteristics identified a high-serum lactate dehydrogenase (LDH) value as being associated with blast 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 trials of TPO for MDS.

Original languageEnglish
Pages (from-to)112-119
Number of pages8
JournalStem Cells
Volume18
Issue number2
Publication statusPublished - 2000
Externally publishedYes

Fingerprint

Thrombopoietin
Myelodysplastic Syndromes
Refractory Anemia with Excess of Blasts
Thrombopoiesis
L-Lactate Dehydrogenase
Cell Cycle
Thrombopoietin Receptors
Lymphocyte Activation
Reverse Transcriptase Polymerase Chain Reaction
Serum
Acute Myeloid Leukemia
Thrombocytopenia

Keywords

  • Blast proliferation
  • Myelodysplastic syndromes
  • Thrombopoietin

ASJC Scopus subject areas

  • Cell Biology

Cite this

Effect of thrombopoietin on proliferation of blasts from patients with myelodysplastic syndromes. / Luo, Shan Shun; Ogata, Kiyoyuki; Yokose, Norio; Kato, Takashi; Kazuo, Dan.

In: Stem Cells, Vol. 18, No. 2, 2000, p. 112-119.

Research output: Contribution to journalArticle

Luo, SS, Ogata, K, Yokose, N, Kato, T & Kazuo, D 2000, 'Effect of thrombopoietin on proliferation of blasts from patients with myelodysplastic syndromes', Stem Cells, vol. 18, no. 2, pp. 112-119.
Luo, Shan Shun ; Ogata, Kiyoyuki ; Yokose, Norio ; Kato, Takashi ; Kazuo, Dan. / Effect of thrombopoietin on proliferation of blasts from patients with myelodysplastic syndromes. In: Stem Cells. 2000 ; Vol. 18, No. 2. pp. 112-119.
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