Suppression of Normal Hematopoiesis in Acute Leukemia: Effect of Leukemic Cells on Bone Marrow Stromal Cells and Hematopoietic Progenitor Cells.

Aoyagi, Masakuni; Furusawa, Shinpei; Waga, Kazuo; Tsunogake, Satoshi; Shishido, Hideo

doi:10.2169/internalmedicine.33.288

Cited by 6 publications

(6 citation statements)

References 32 publications

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“…Direct contact can go beyond membrane receptor interactions. Prevention of vitamin-D-induced differentiation of HL-60 cells was shown to depend on tight adherence be- Functional importance for chemotaxis [191] Interactions promoting growth of AML cells Prevention of apoptosis [16] Prevention of differentiation [213] Induction of proliferation [187] Provision of growth factors [16] Paracrine growth factor loops [93,171] Interactions preventing growth of AML cells Induction of differentiation [187] Inhibition of survival and proliferation [39,70,71] Interactions preventing growth of stroma cells Inhibition of proliferation [163] Lysis of mature cells [5] tween leukemic cells and stroma cells, which allowed transfer of intracellular material through gap junctions from one cell type to the other [213]. Contrasting with these growth-promoting stroma effects is the observation that, under long-term culture conditions, the leukemic cell population may gradually disappear and be replaced by normal hematopoietic cells (Table 2) [39,70,186,190].…”

Section: Stroma-related Properties Of Aml Cellsmentioning

confidence: 99%

“…In addition to slowing stroma formation, human AML cell lines were shown to induce cell death in established stromal layers and to prevent stroma binding of hematopoietic precursor cells [5]. These effects were mediated by a humoral mechanism distinct from TNF-a or IFN-a [5].…”

Section: Stromal Abnormalities In Amlmentioning

confidence: 99%

“…In further analogy to AML, the reduction in fibroblast precursor numbers appears to be caused by the leukemic cells [163]. More recent work using B-and Tlymphoblastic cell lines instead of primary ALL cells showed suppression of stroma development and destruction of established stroma layers by an unidentified humoral mechanism [5]. Lysis of stroma cells was also observed in cultures of Ebstein-Barr virus-transformed B cell lines, and in this case it was mediated by spermidine and spermine [176].…”

Section: Stromal Abnormalities In Allmentioning

confidence: 99%

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Stromal abnormalities in neoplastic bone marrow diseases

Dührsen

Hossfeld

1996

Annals of Hematology

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Bone marrow malignancies are clonal disorders resulting from neoplastic transformation of hematopoietic stem or progenitor cells. Similar to their normal counterparts, transformed blood-forming cells remain dependent on signals from the hematopoiesis-regulating stromal environment for survival and proliferation. There is increasing evidence that the microenvironment may also take a more active part in the disease process. A review of the literature on stromal abnormalities in the leukemias, the myelodysplastic syndromes, and multiple myeloma reveals three principal mechanisms by which stromal derangements can contribute to the evolution of a neoplastic disease. In the simplest case, neoplastic blood-forming cells induce reversible changes in stroma function or composition which result in improved growth conditions for the malignant cells ('malignancy-induced microenvironment'). In the second setting, functionally abnormal end cells derived from the malignant clone become an integral part of the stroma system, selectively stimulating the neoplastic cells and inhibiting normal blood cell formation ('malignant microenvironment'). In the third condition, the emergence of a neoplastic cell population is the consequence of a primary stroma lesion characterized by inability to control regular blood cell formation ('malignancy-inducing microenvironment'). The perception of different stroma-related disease mechanisms may eventually lead to the development of alternative therapeutic approaches.

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Section: Stroma-related Properties Of Aml Cellsmentioning

confidence: 99%

Section: Stromal Abnormalities In Amlmentioning

confidence: 99%

Section: Stromal Abnormalities In Allmentioning

confidence: 99%

See 1 more Smart Citation

Stromal abnormalities in neoplastic bone marrow diseases

Dührsen

Hossfeld

1996

Annals of Hematology

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“…For example, Aoyagi et al [106] have shown that various leukemic cell lines and cell line-conditioned media can inhibit the growth of stromal cells and of adherent long-term bone marrow culture cells. This inhibition was most prominent when the leukemic cells were cocultured directly with the marrow stromal cells as opposed to the case where a mem brane separated the leukemic cells and the stromal monolayers.…”

Section: Effects Of Adhesion On Leukemic Cellsmentioning

confidence: 99%

Expression and Function of Adhesion Receptors in Acute Myelogenous Leukemia: Parallels with Normal Erythroid and Myeloid Progenitors

Liesveld¹

1997

Acta Haematol

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A variety of adhesion receptors are expressed on the blast cells in patients with acute myelogenous leukemia. The panel of receptors expressed demonstrates heterogeneity just as there is morphologic, histochemical, cytogenetic, and molecular genetic variation between various cases of acute myelogenous leukemia. The adhesion receptors expressed contain representatives of all the main classes of adhesion receptors, but often there is no correlation of the adhesion receptor phenotype with the morphologic or clinical features of acute myelogenous leukemia. These receptors function in interactions of myelogenous leukemia blasts with the cellular and matrix components of the marrow microenvironment, and there is evidence that they are involved in blast release from marrow and in homing of blasts to extrameduilary sites. Evidence is starting to accumulate suggesting that adhesive interactions may influence the proliferation and survival of leukemic cells, but the precise role that these molecules play in the generation and sustenance of the leukemic state remains undetermined.

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“…Previously, the misbalance in hematopoiesis in patients with hematologic malignancies was suggested to be caused by factors excreted by malignant cells. 44 In addition, disturbed support of hematopoiesis by MSCs might contribute to dysplasia in these patients. CXCL12 expression was decreased in JMML-MSCs, as was also previously shown in studies on MSC from adult CML and pediatric ALL patients.…”

Section: A C B Dmentioning

confidence: 99%

Gene-expression and in vitro function of mesenchymal stromal cells are affected in juvenile myelomonocytic leukemia

et al. 2015

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An aberrant interaction between hematopoietic stem cells and mesenchymal stromal cells has been linked to disease and shown to contribute to the pathophysiology of hematologic malignancies in murine models. Juvenile myelomonocytic leukemia is an aggressive malignant disease affecting young infants. Here we investigated the impact of juvenile myelomonocytic leukemia on mesenchymal stromal cells. Mesenchymal stromal cells were expanded from bone marrow samples of patients at diagnosis (n=9) and after hematopoietic stem cell transplantation (n=7; from 5 patients) and from healthy children (n=10). Cells were characterized by phenotyping, differentiation, gene expression analysis (of controls and samples obtained at diagnosis) and in vitro functional studies assessing immunomodulation and hematopoietic support. Mesenchymal stromal cells from patients did not differ from controls in differentiation capacity nor did they differ in their capacity to support in vitro hematopoiesis. Deep-SAGE sequencing revealed differential mRNA expression in patient-derived samples, including genes encoding proteins involved in immunomodulation and cell-cell interaction. Selected gene expression normalized during remission after successful hematopoietic stem cell transplantation. Whereas natural killer cell activation and peripheral blood mononuclear cell proliferation were not differentially affected, the suppressive effect on monocyte to dendritic cell differentiation was increased by mesenchymal stromal cells obtained at diagnosis, but not at time of remission. This study shows that active juvenile myelomonocytic leukemia affects the immune responserelated gene expression and function of mesenchymal stromal cells. In contrast, the differential gene expression of hematopoiesis-related genes could not be supported by functional data. Decreased immune surveillance might contribute to the therapy resistance and progression in juvenile myelomonocytic leukemia.

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Suppression of Normal Hematopoiesis in Acute Leukemia: Effect of Leukemic Cells on Bone Marrow Stromal Cells and Hematopoietic Progenitor Cells.

Cited by 6 publications

References 32 publications

Stromal abnormalities in neoplastic bone marrow diseases

Stromal abnormalities in neoplastic bone marrow diseases

Expression and Function of Adhesion Receptors in Acute Myelogenous Leukemia: Parallels with Normal Erythroid and Myeloid Progenitors

Gene-expression and in vitro function of mesenchymal stromal cells are affected in juvenile myelomonocytic leukemia

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