Cytogenetic and molecular cytogenetic profile of bone marrow-derived mesenchymal stromal cells in chronic and acute lymphoproliferative disorders

Abstract

The possibility that human mesenchymal stromal cells (hMSC) may derive from the malignant clone in hematological malignancies (HM) is a controversial issue. In order to clarify hMSC origin and disclose possible cytogenetic heterogeneity in hMSC belonging to different patients, bone marrow (BM)-derived hMSC samples from chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL) were expanded in culture, characterized by flow cytometry, and screened by conventional cytogenetic analysis and fluorescent in situ hybridization for the presence of possible cytogenetic aberrations, related or not to the hematopoietic neoplastic clone. Our data showed that the presence of cytogenetic aberrations in successfully expanded HM-MSC stromal layers derives from the persistence of contaminating hemopoietic cells (HC), which is greatly supported by in vitro culture conditions that could mimic in vivo microenvironmental niche. Interestingly, the presence of binucleated HM-MSC maintaining a diploid numerical setting has been also detected, while aneuploidies were observed more frequently in mononucleated HM-MSC from patients with an altered karyotype than in patients with a normal karyotype and controls. In conclusion, here,we showed that in ALL and in CLL, the BM-MSC has a normal karyotype, thus supporting a distinct origin from hematopoietic cells (HC). The presence of in vitro hMSC aneuploidy is associated with lymphoid neoplasias carrying chromosome abnormalities, suggesting that hMSC should be characterized before clinical application. The adequacy of hMSC cytogenetic characterization here proposed could represent a "prerequisite" to standardize the hMSC analysis before their use in the autologous setting and cellular therapy. © Springer-Verlag 2012