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Lenalidomide consolidation treatment in patients with multiple myeloma suppresses myelopoieses but spares erythropoiesis
Author(s) -
Wilk Christian Matthias,
Heinzler Niklas,
Boquoi Amelie,
Cadeddu RonPatrick,
Strapatsas Tobias,
Dienst Ariane,
Majidi Fatemeh,
Deenen René,
Bruns Ingmar,
Schroeder Thomas,
Köhrer Karl,
Haas Rainer,
Kobbe Guido,
Fenk Roland
Publication year - 2016
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30257
Subject(s) - lenalidomide , multiple myeloma , erythropoiesis , progenitor cell , cancer research , haematopoiesis , stem cell , fetal hemoglobin , medicine , thalidomide , bone marrow , plerixafor , pharmacology , cxcr4 , immunology , biology , anemia , fetus , microbiology and biotechnology , pregnancy , genetics , chemokine , receptor
New drugs for the treatment of multiple myeloma (MM) comprise immunomodulatory substances such as lenalidomide and related compounds. While lenalidomide has found its way into first‐line treatment as well as into relapse therapy, little is known about lenalidomide effects on normal hematopoietic stem and progenitor cells (HSPCs). In this study, we investigated whether HSPCs are influenced by lenalidomide on a phenotypic, functional and gene expression level. For that purpose, samples from patients with MM were obtained who underwent equivalent first‐line treatment including induction therapy, cytotoxic stem cell mobilization and high‐dose melphalan therapy followed by autologous blood stem cell transplantation and a subsequent uniform lenalidomide consolidation treatment within a prospective clinical trial. We found that after six months of lenalidomide therapy, the number of CD34 + HSPCs decreased. Additionally, lenalidomide affects the numerical composition of hematopoietic cells in the bone marrow while it does not affect long‐term HSPC proliferation in vitro . We found a significant amplification of fetal hemoglobin (HbF) expression on a transcriptional level and can confirm a stimulated erythropoiesis on a phenotypic level. These effects were accompanied by silencing of the TGF‐β signaling pathway on the gene expression and protein level that is known to be amplified in active MM. However, these pleiotropic effects gave no evidence for mutagenic potential. In conclusion, lenalidomide does not exert long‐term effects on proliferation of HSPCs but instead promotes erythropoiesis by shifting hemoglobin expression toward HbF and by silencing the TGF‐β signaling pathway.