Mesenchymal stem cells from patients with chronic myeloid leukemia do not express BCR-ABL and have absence of chimerism after allogeneic bone marrow transplant

Abstract

Bone marrow is a heterogeneous cell population which includes hematopoietic and mesenchymal progenitor cells. Dysregulated hematopoiesis occurs in chronic myelogenous leukemia (CML), being caused at least in part by abnormalities in the hematopoietic progenitors. However, the role of mesenchymal stem cells (MSCs) in CML has not been well characterized. The objectives of the present study were to observe the biological characteristics of MSCs from CML patients and to determine if MSCs originate in part from donors in CML patients after bone marrow transplantation (BMT). We analyzed MSCs from 5 untreated patients and from 3 CML patients after sexmismatched allogeneic BMT. Flow cytometry analysis revealed the typical MSC phenotype and in vitro assays showed ability to differentiate into adipocytes and osteoblasts. Moreover, although some RT-PCR data were contradictory, combined fluorescence in situ hybridization analysis showed that MSCs from CML patients do not express the bcr-abl gene. Regarding MSCs of donor origin, although it is possible to detect Y target sequence by nested PCR, the low frequency (0.14 and 0.34%) of XY cells in 2 MSC CML patients by fluorescence in situ hybridization analysis suggests the presence of contaminant hematopoietic cells and the absence of host-derived MSCs in CML patients. Therefore, we conclude that MSCs from CML patients express the typical MSC phenotype, can differentiate into osteogenic and adipogenic lineages and do not express the bcr-abl gene. MSCs cannot be found in recipients 12 to 20 months after BMT. The influence of MSCs on the dysregulation of hematopoiesis in CML patients deserves further investigation.

Isolation, Characterization and Application of BCR-ABL-ve Mesenchymal Stem Cells Derived from Peripheral Blood of Chronic Myeloid Leukemia (CML) in Enhancing Potentiality of Bone Marrow Transplantation in CML Patients

“…We further assessed these stem cells for presence or absence of BCR/ABL transcript and we found that cells isolated and grown from CML patients were BCR/ABL -ve cells and therefore we designated these cells as BCR/ABL -ve cell line. A similar study was carried out by Carrara et al [17] and our results are obtained in concordance with them. Upon establishment of the BCR/ABL -ve cell line and thorough observation of phenotypic characters through phase contrast microscopy and Giemsa staining, we could taper down to the idea of presence of mesenchymal stem cells.…”

“…The data collected through these experiments suggest that the cells are likely normal and do not seem to be obnoxious in any way though derived from a patient in blast crisis of CML. These results of attaining normal MSCs are in concordance with previous studies which have reported isolation of normal MSCs from CML patients [17]. Many studies have pointed towards the use of MSCs in treating CML.…”

Alteration of cellular and immune‐related properties of bone marrow mesenchymal stem cells and macrophages by K562 chronic myeloid leukemia cell derived exosomes

“…The role of tumor-derived exosomes in tumor niche dysfunction is complex, and they can participate in homing, niche-immune responses, angiogenesis, tumor cell growth, and immunosuppression (Whiteside, 2016). As per our knowledge, the functional properties and secretome of MSC are altered in the leukemic bone marrow (Carrara et al, 2007, Geyh et al, 2016, López et al, 2014. We hypothesized that CML-derived exosomes have a critical role in creating inflammatory and tumor-favorable local condition in BM-MSCs and macrophages.…”

Multilineage potential of adult human mesenchymal stromal cells derived from bone marrow of patients with polycytaemia vera

“…Isolated MSCs from the BM of patients with chronic myeloid leukemia did not demonstrate any presence of the Philadelphia chromosome, retained their ability to differentiate into osteoblasts and could support expansion of cord blood stem cells (Jootar et al 2006). MSCs from patients with chronic myeloid leukemia expressed the typical MSCs phenotype and differentiated into osteogenic and adipogenic lineages (Carrara et al 2007). The supposition of the risk that MSCs after the in vitro cultivation prepared for application to the patient would be contaminated by hematopoietic cells is low, since cultures of human MSCs become free of hematopoietic precursors after one or two passages (Sekiya et al 2002) and according to our experiences they are washed out after the first cultivation medium exchange after the seeding.…”