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Mesenchymal stromal cells (MSCs) are an essential cell type of the hematopoietic microenvironment. Concerns have been raised about the possibility that MSCs undergo malignant transformation. Several studies, including one from our own group, have shown the presence of cytogenetic abnormalities in MSCs from leukemia patients. The aim of the present study was to compare genetic aberrations in hematopoietic cells (HCs) and MSCs of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients. Cytogenetic aberrations were detected in HCs from 25 of 51 AML patients (49%) and 16 of 43 MDS patients (37%). Mutations of the FLT3 and NPM1 genes were detected in leukemic blasts in 12 (23%) and 8 (16%) AML patients, respectively. Chromosomal aberrations in MSCs were detected in 15 of 94 MDS/AML patients (16%). No chromosomal abnormalities were identified in MSCs of 36 healthy subjects. We demonstrate herein that MSCs have distinct genetic abnormalities compared with leukemic blasts. We also analyzed the main characteristics of patients with MSCs carrying chromosomal aberrations. In view of these data, the genetic alterations in MSCs may constitute a particular mechanism of leukemogenesis.

Objective: Bone marrow mesenchymal stroma cells (BMSC) are key components of the hematopoietic microenvironment. The question of whether BMSC from patients with hematological disorders have cytogenetic abnormalities is discussed controversially, some studies indicating that they are cytogenetically normal and others providing evidence of their aberrations., Patients and Methods: We performed standard and molecular cytogenetic analyses of both hematopoietic cells and BMSC from 31 patients with myelodysplastic syndrome (MDS, n = 18) and acute myeloid leukemia (AML, n = 13) and 7 healthy individuals. Mononuclear cells were isolated from fresh bone marrow aspirates at the time of initial diagnosis for cytogenetic analysis of hematopoietic cells (HC) and selection of BMSC., Results: Clonal cytogenetic aberrations were observed in HC from 8 (44%) MDS and 8 (61%) AML patients. Cytogenetic analyses of BMSC were successfully performed in 27 of the 31 cases. Structural chromosomal aberrations, including t(1;7), t(4;7), t(7;9), t(7;10), t(7;19), t(15;17), and others, were detectable in BMSC from 7 of 16 (44%) MDS and 6 of 11 (54%) AML patients. The breakpoints of chromosomes in BMSC were typical for leukemia aberrations. Two patients showed clonal chromosomal markers., Conclusions: BMSC from MDS and AML patients show chromosomal abnormalities. Although the majority of cytogenetic aberrations in BMSC were not clonal and differed from chromosomal markers in HC from the same individual, detection of typical chromosomal changes in BMSC suggests enhanced genetic susceptibility of these cells in MDS/AML. This may indicate potential involvement of BMSC in the pathophysiology of MDS/AML.

Myelodysplastic syndrome (MDS) is a heterogeneous group of myeloid disorders. MDS remains a disease of elderly patients; moreover, the incidence of high risk MDS is proportionally greater in elderly patients, with increased frequency of secondary acute myeloid leukemia, as well as adverse cytogenetic abnormalities. Allogeneic stem cell transplantation is a therapeutic approach with known curative potential for patients with MDS that allows the achievement of long-term disease control. Numerous controversies still exist regarding transplantation in MDS: timing of transplantation, disease status at transplantation and comorbidity, conditioning intensity, pretransplant therapy, and stem cell source. Various transplant modalities of different intensities and alternative donor sources are now in use. Current advances in transplant technology are allowing the consideration of older patients. This should result in a greater number of older patients benefiting from this potentially curative treatment modality. Despite advances in transplantation technology, there is still considerable morbidity and mortality associated with this approach. Nevertheless, with the introduction of reduced-intensity conditioning and thereby reduced early mortality, transplant numbers in MDS patients have significantly increased. Moreover, recent new developments with innovative drugs, including hypomethylating agents, have extended the therapeutic alternatives for MDS patients. Hypomethylating agents allow the delay of allogeneic stem cell transplantation by serving as an effective and well-tolerated means to reduce disease burden. [ABSTRACT FROM AUTHOR]