Published online 22 September 2009
Haematologica, Vol 95, Issue 3, 406-414 doi:10.3324/haematol.2009.010876
Copyright © 2010 by Ferrata Storti Foundation
Maria Ximeri1 ,
Athanasios Galanopoulos2 ,
Mirjam Klaus1 ,
Agapi Parcharidou3 ,
Krinio Giannikou1 ,
Maria Psyllaki1 ,
Argyrios Symeonidis4 ,
Vasiliki Pappa5 ,
Zafiris Kartasis6 ,
Dimitra Liapi7 ,
Eleftheria Hatzimichael8 ,
Styliani Kokoris9 ,
Penelope Korkolopoulou10 ,
Constantina Sambani11 ,
Charalampos Pontikoglou1 ,
Helen A. Papadaki1 on behalf of the Hellenic MDS Study Group
Haematologica, Vol 95, Issue 3, 406-414 doi:10.3324/haematol.2009.010876
Copyright © 2010 by Ferrata Storti Foundation
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Myelodysplastic Syndromes |
Effect of lenalidomide therapy on hematopoiesis of patients with myelodysplastic syndrome associated with chromosome 5q deletion
1 Dept. of Hematology, University of Crete School of Medicine, Heraklion;
2 Dept. of Clinical Hematology, "G.Gennimatas" Hospital, Athens;
3 Third Dept. of Internal Medicine, Red Cross Hospital "Korgialenio Benakio", Athens;
4 Stem Cell Transplantation Unit, Dept. of Internal Medicine, Hematology Division, University of Patras Medical School, Patras;
5 Hematology Unit, Second Dept. of Internal Medicine-Propaedeutic, Attikon University General Hospital, University of Athens, Athens;
6 Dept. of Hematology, General Hospital of Chalkis, Chalkis;
7 Dept. of Hematology, "Venizeleion" Hospital, Heraklion;
8 Dept. of Hematology, University of Ioannina, Ioannina;
9 Dept. of Hematology, National Kapodistrian University of Athens, Laikon University Hospital, Athens;
10 First Dept. of Pathology, National and Kapodistrian University of Athens, Laiko Hospital, Athens;
11 Laboratory of Health Physics & Environmental Hygiene, Inst. NT-RP, National Center for Scientific Research (NCSR) ‘Demokritos’, Athens, Greece
Correspondence: Helen A Papadaki, MD, PhD, Professor of Hematology, Department of Hematology, University Hospital of Heraklion, P.O. Box 1352, Heraklion, Crete, Greece., E-mail: epapadak{at}med.uoc.gr
Background: Lenalidomide improves erythropoiesis in patients with low/intermediate-1 risk myelodysplastic syndrome and interstitial deletion of the long arm of chromosome 5 [del(5q)]. The aim of this study was to explore the effect of lenalidomide treatment on the reserves and functional characteristics of bone marrow hematopoietic progenitor/precursor cells, bone marrow stromal cells and peripheral blood lymphocytes in patients with low/intermediate-1 risk myelodysplastic syndrome with del(5q).
Design and Methods: We evaluated the number and clonogenic potential of bone marrow erythroid/myeloid/megakaryocytic progenitor cells using clonogenic assays, the apoptotic characteristics and adhesion molecule expression of CD34+ cells by flow cytometry, the hematopoiesis-supporting capacity of bone marrow stromal cells using long-term bone marrow cultures and the number and activation status of peripheral blood lymphocytes in ten patients with low/intermediate-1 risk myelodysplastic syndrome with del(5q) receiving lenalidomide.
Results: Compared to baseline, lenalidomide treatment significantly decreased the proportion of bone marrow CD34+ cells, increased the proportion of CD36+/GlycoA+ and CD36–/GlycoA+ erythroid cells and the percentage of apoptotic cells within these cell compartments. Treatment significantly improved the clonogenic potential of bone marrow erythroid, myeloid, megakaryocytic colony-forming cells and increased the proportion of CD34+ cells expressing the adhesion molecules CD11a, CD49d, CD54, CXCR4 and the SLAM antigen CD48. The hematopoiesis-supporting capacity of bone marrow stroma improved significantly following treatment, as demonstrated by the number of colony-forming cells and the level of stromal-derived factor-1
and intercellular adhesion molecule-1 in long-term bone marrow culture supernatants. Lenalidomide treatment also increased the proportion of activated peripheral blood T lymphocytes.
Conclusions: The beneficial effect of lenalidomide in patients with lower risk myelodysplastic syndrome with del(5q) is associated with significant increases in the proportion of bone marrow erythroid precursor cells and in the frequency of clonogenic progenitor cells, a substantial improvement in the hematopoiesis-supporting potential of bone marrow stroma and significant alterations in the adhesion profile of bone marrow CD34+ cells.
Key words: lenalidomide, hematopoiesis, MDS, chromosome 5q deletion.
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