Functional and immunophenotypic characteristics of isolated CD105+ and fibroblast+ stromal cells from AML: implications for their plasticity along endothelial lineage

Alteration Analysis of Bone Marrow Mesenchymal Stromal Cells from De Novo Acute Myeloid Leukemia Patients at Diagnosis

“…Of note, L-MSC hematopoiesis-supporting activity was normal regardless of their proliferative capacity and despite lower VCAM-1 expression. Normal HPC production has also been reported in a previous study using immunoselected AMLMSCs [10], in contrast to other studies where different (sometimes suboptimal) culture conditions of MSCs were used [9,12,55]. Our findings are consistent with a very recent study in a murine model of AML indicating that BM microenvironment retains in vivo supporting activity of normal hematopoiesis [56].…”

“…The main abnormality detected in L-MSCs was a clear decrease in their proliferative potential, as recently reported in AML [9,10,[12][13][14]. Such proliferation defects have also been described in MSCs from several other hematopoietic disorders, such as acute lymphoblastic leukemia (ALL) [31,32], chronic lymphocytic leukemia (CLL) [33,34], and especially MDS [16,17,35,36].…”

“…Moreover, L-MSC growth impairment can be restored with the repetition of chemotherapy cycles [32] or at diagnosis when most leukemic cells are eliminated by immunoselection of CD105 pos MSCs [10]. It has been shown that fragmented DNA released by AML cells may enter MSC nuclei and induce DNA DSBs and cell death [40].…”

“…MSCs are multipotent cells that give rise to vascular smooth muscle cells, adipocytes, osteoblasts of the BM, and also chondroblasts. Alterations of the BM stromal cell compartment have been shown in de novo AML, including a reduction in the number of fibroblasts and adipocytes and a decreased growth capacity [9][10][11][12][13][14]. However, it is not yet evident if MSC long-term hematopoietic-supporting activity in AML at diagnosis is intrinsically impaired [12] or not [10].…”

“…Alterations of the BM stromal cell compartment have been shown in de novo AML, including a reduction in the number of fibroblasts and adipocytes and a decreased growth capacity [9][10][11][12][13][14]. However, it is not yet evident if MSC long-term hematopoietic-supporting activity in AML at diagnosis is intrinsically impaired [12] or not [10]. Otherwise, several recent reports have highlighted the abnormal MSC function in chronic preleukemic diseases such as myelodysplastic syndromes (MDSs) [15][16][17] in contrast to chronic myelogenous leukemia (CML) [18,19].…”