Clinical significance of human bone marrow stromal cell colonies in acute leukemias

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Bone marrow-derived fibroblastoid colony-forming cells (CFU-F) and granulocyte/macrophage precursor cells (CFU-GM) were studied in patients with acute leukemia. The numbers of CFU-F and CFU-GM were significantly lower in patients with acute myelogenous leukemia (AML) and acute lymphocytic leukemia (ALL) at diagnosis than in normal subjects, although patients with AML had a very wide range of CFU-F colony-forming efficiency. However, a suppressive effect of leukemic cells on normal CFU-F colony formation was not observed. CFU-F and CFU-GM in patients with acute leukemia recovered to normal levels when complete remission (CR) was achieved and decreased again at relapse. Serial studies showed that the increase in CFU-F preceded the recovery of CFU-GM. In AML, furthermore, patients who achieved CR had a higher number of CFU-F than patients without CR, suggesting that the CFU-F level at diagnosis may contribute to the prediction of the likelihood of remission induction in patients with AML.

Section: Discussionmentioning

confidence: 91%

Serial Studies of Bone Marrow-Derived Fibroblastoid Colony-Forming Cells and Granulocyte/Macrophage Precursor Cells in Patients with Acute Leukemia

Katsuno¹,

Hirata²,

Kaneko³

et al. 1986

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“…Assay for CFU-F and Adipocyte Colony-Forming Capacity (adipo-CFC) These assays were performed as previously described elsewhere [4,5]. Briefly, 106 marrow cells were suspended in 3 ml of McCoy's 5A medium supplemented with 25% horse serum or 15% fetal calf serum (FCS), and 10'6 mol/1 hydrocortisone sodium phosphate (Merk-Banyu, Tokyo, Japan) and were then cultured in triplicated dishes at 37°C in a humidified atmosphere of air plus 5% C 0 2.…”

Section: Patients and Cellsmentioning

confidence: 99%

“…During recent years, bone marrow stromal cells of various hematological disor ders were studied using in vitro culture systems [2][3][4][5][6]. In our previous study, we showed that the number of bone marrow-derived fibroblastoid colony-forming cells (CFU-F) was decreased in cases of acute leu kemia, but was within normal limits in cases of other hematological diseases [4][5][6]. Furthermore, we dem onstrated that bone marrow adipocyte colony forma tion was closely associated with regenerating he mopoiesis in our studies of stromal cells of acute leukemia and various anemias [5,6].…”

Section: Introductionmentioning

confidence: 99%

Bone Marrow Stromal Cells in Myeloproliferative Disorders

Hirata¹,

Takahira

Kaneko

et al. 1989

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The number of bone marrow-derived fibroblastoid colony-forming cells (CFU-F) and the production of colony-stimulating activity (CSA) by bone marrow stromal cells were studied in 71 patients with myeloproliferative disorders (MPD). The numbers of CFU-F in chronic-phase chronic myelogenous leukemia (CML), polycythemia vera (PV) and essential thrombocythemia (ET) were not different from those in normal subjects. However, the number of CFU-F in acute-phase CML was markedly decreased. Bone marrow adipocyte colony-forming capacity (adipo-CFC), which was previously shown to reflect both the number of pre-adipocytes and the stromal cell function in vivo, was increased in patients with chronic-phase CML, PV and ET, but was absent in acute-phase CML patients. The production of CSA by marrow stromal cells of MPD patients, however, was not different from that of normal subjects. These results suggest that the characteristics of marrow stromal and its precursor cells of chronic-phase MPD patients were not different from those of normal subjects, however, they became changed in acute-phase CML patients.

“…Both the pathological hematopoiesis and the cytostatic treatment itself lead to a decrease in the CFU-F concentration [18,19,20]. Various methods of conditioning the patients prior to hematopoietic stem cell (HSC) transplantation are accompanied by a sharp decrease in the clonal stromal precursor number [21, 22].…”

Section: Introductionmentioning

confidence: 99%

Sensitivity of Mesenchymal Stem Cells and Their Progeny to Medicines Used for the Treatment of Hematoproliferative Diseases

Nifontova¹,

Svinareva²,

Petrova³

et al. 2008

Background/Aims: The influence of cytostatic medicines on mesenchymal stem cells (MSC) and their progeny, fibroblastic colony-forming units (CFU-F), was investigated. Methods: Mice were treated with busulfan, cyclophosphamide, cytarabine, methotrexate and bortezomib, as used in clinical practice. MSC and CFU-F were analyzed 3 days and 6 weeks after the treatment termination. To estimate MSC numbers, the ectopic foci formation method was used. Briefly, a donor bone marrow plug was transplanted under the renal capsule of a syngeneic animal, leading to ectopic foci formation. The systemic response of the hematopoietic microenvironment to these drugs was studied using the same method applied to recipients pretreated with the medicines. Results: CFU-F concentration was halved in the bone marrow of mice treated with busulfan, methotrexate and cyclophosphamide, and was not restored for the next 6 weeks. Proliferative potential and differentiation abilities of MSC were not affected by these medicines. The enlargement of foci size in mice treated with cytostatic agents was not conditioned by MSC, but by more mature stromal precursor cells. Conclusions: Cytostatic medicines affect stromal precursors in 2 ways: they decrease CFU-F concentration in the ‘steady-state’ bone marrow, while stimulating growth of the stromal microenvironment during its de novo formation. MSC are not sensitive to the cytostatic agents used.