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 sex-mismatched 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.
Highlights
Bone marrow (BM) is composed of at least two systems, i.e., the hematopoietic tissue proper and the stroma [1,2]
We determined the presence of the bcrabl gene in the Mesenchymal stem cells (MSCs) of BM from Chronic myeloid leukemia (CML) patients in order to determine the role of MSCs in the genesis of CML
We investigated whether this mutation might occur in a more primitive progenitor cell population common to MSCs and hematopoietic stem cells (HSCs), as observed for endothelial cells of patients with CML [9,10]
Summary
Bone marrow (BM) is composed of at least two systems, i.e., the hematopoietic tissue proper and the stroma [1,2]. Mesenchymal stem cells (MSCs) are important constituents of this microenvironment and are characterized as adult, non-hematopoietic stem cells (HSCs) which, after an adequate stimulus, can differentiate morphologically and functionally into different cell lines including the stroma, which gives support to hematopoiesis, adipocytes, chondrocytes, myocytes, astrocytes, tenocytes, and hepatocytes [3,4]. Chronic myeloid leukemia (CML) is a myeloproliferative disease originating in multipotent HSCs which acquire the reciprocal translocation t(9;22)(q34;q11) characterized cytogenetically by the presence of the Philadelphia (Ph1) chromosome This translocation intercalates portions of the cabl protooncogene in chromosome 9 with the c-bcr gene in chromosome 22, forming a hybrid bcr-abl gene that codes for the BCRABL oncoprotein [6,7,8]
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