In vitro crosstalk between fibroblasts and native human acute myelogenous leukemia (AML) blasts via local cytokine networks results in increased proliferation and decreased apoptosis of AML cells as well as increased levels of proangiogenic Interleukin 8

Ryningen, Anita; Wergeland, Line; Glenjen, Nils; Gjertsen, Bjørn Tore; Bruserud, Øystein

doi:10.1016/j.leukres.2004.06.008

Cited by 62 publications

(65 citation statements)

References 26 publications

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“…8 Primary AML cells were cultured with various stromal cells that support AML cell proliferation. 14,18 We detected supraadditive levels of Ang-1 in cocultures of primary AML cells together with the two fibroblast cell lines and the osteosarcoma cell line Cal-72. The high Ang-1 levels in cocultures are mainly due to AML cells, because the levels found in cocultures correlated significantly with levels in AML cell cultures.…”

Section: Discussionmentioning

confidence: 82%

“…The high Ang-1 levels in cocultures are mainly due to AML cells, because the levels found in cocultures correlated significantly with levels in AML cell cultures. Although stromal cells usually increase the proliferation of AML cells, 14,18 increased levels of Ang-1 in cocultures cannot be explained merely by the altered proliferation; as increased proliferation was not always associated with increased release of Ang-1 and vice versa (data not shown). Taken together, our results demonstrate that the bidirectional crosstalk between AML cells and neighboring nonleukemic cells will modulate local Ang-1 and Ang-2 levels, but the capability of constitutive release by the AML cells still has a major influence.…”

Section: Discussionmentioning

confidence: 91%

“…14,18 The observed relationship between NPM1 mutations and Ang-1 levels both at the gene expression and protein levels, suggests that angiopoietin associated angioregulation is important especially for patients with NPM1 mutations. Increased protein release of proangiogenic CXCL8 was also associated with NPM1 mutations, and a similar increase in CCL3, CCL4 and CXCL1 levels is expected because the constitutive release by primary AML cells of these chemokines is correlated with CXCL8 release.…”

Section: Discussionmentioning

confidence: 99%

“…Spontaneous in vitro apoptosis of AML cells cultured for 72 h in Stem Span medium was assayed by flow cytometry. 18 Tie2 expression was detected by staining with phycoerythrin-conjugated anti-Tie2 monoclonal antibody and compared with isotypic controls (R&D Systems).…”

Section: Non-leukemic Cell Lines and Primary Bmscsmentioning

confidence: 99%

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Release of angiopoietin-1 by primary human acute myelogenous leukemia cells is associated with mutations of nucleophosmin, increased by bone marrow stromal cells and possibly antagonized by high systemic angiopoietin-2 levels

et al. 2007

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Non-leukemic Cell Lines and Primary Bmscsmentioning

confidence: 99%

See 2 more Smart Citations

Release of angiopoietin-1 by primary human acute myelogenous leukemia cells is associated with mutations of nucleophosmin, increased by bone marrow stromal cells and possibly antagonized by high systemic angiopoietin-2 levels

et al. 2007

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“…As described previously (Bruserud et al, 2000(Bruserud et al, , 2003Glenjen et al, 2004) Coculture of AML cells and normal BMSC. The cultures were prepared as described Glenjen et al, 2004;Ryningen et al, 2005 Analysis of AML cell cytokine secretion…”

Section: Reagents For Tissue Culturementioning

confidence: 99%

The proteasome inhibitors bortezomib and PR‐171 have antiproliferative and proapoptotic effects on primary human acute myeloid leukaemia cells

et al. 2007

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SummaryProteasome inhibitors represent a new class of antineoplastic drugs that are considered in the treatment of haematological malignancies. We compared the effects of the reversible proteasome inhibitor bortezomib (Velcade®) and the epoxomicin derivative PR‐171, an irreversible inhibitor, on primary human acute myeloid leukaemia (AML) cells. Both drugs inhibited autocrine‐ and cytokine‐dependent proliferation of primary AML blasts when tested at nanomolar levels (0·1–100 nmol/l). The antiproliferative effect was independent of basal chymotrypsin‐like proteasome activity (showing a 20‐fold variation between patients), genetic abnormalities, morphological differentiation and CD34 expression when testing a large group of consecutive patients (n = 54). The effect was retained in cocultures with bone marrow stromal cells. In addition, both drugs enhanced apoptosis. The effect of PR‐171 could be detected at lower concentrations than for bortezomib, especially when testing the influence on clonogenic AML cell proliferation. Both drugs had divergent effects on AML cells’ constitutive cytokine release. Furthermore, both drugs caused a decrease in proliferation and viability when tested in combination with idarubicin or cytarabine. An antiproliferative effect on primary human acute lymphoblastic leukaemia cells was also detected. We conclude that nanomolar levels of the proteasome inhibitors tested had dose‐dependent antiproliferative and proapoptotic effects on primary AML cells in vitro.

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Bone Marrow

Marlein

Rushworth

2018

Encyclopedia of Life Sciences

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The bone marrow is a highly dynamic organ located within the cavities of bones. The main role of the bone marrow is to facilitate the production of all the blood cells required for normal bodily homeostasis. These cells include lymphocytes, granulocytes, macrophages, red blood cells and plasma cells. The bone marrow is composed of many cell types that provide support for haematopoiesis, the blood cell production process. As with any major organ, many diseases can arise from errors in bone marrow function, including nonmalignant disorders such as anaemia and malignant disorders such as leukaemias. Transplantation of the bone marrow can be carried out, providing treatment options to patients suffering from bone marrow‐related disorders. This article will explore the anatomy and the role of the bone marrow, whilst providing an insight into the disorders created by errors in normal bone marrow function. Key Concepts The bone marrow is composed of red and yellow marrow and is the site of haematopoiesis. The primary function of the bone marrow is haematopoiesis – haematopoietic stem cells (HSC) lead to the generation of all blood cells All myeloid and lymphoid cells are generated in the bone marrow, crucial for the innate and adaptive immune systems, along with blood clotting and oxygen circulation. Nonhaematopoietic cells provide key molecules to regulate the process of haematopoiesis. Errors in the bone marrow can results in bone marrow‐related disorders, such as anaemia and leukaemia.

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In vitro crosstalk between fibroblasts and native human acute myelogenous leukemia (AML) blasts via local cytokine networks results in increased proliferation and decreased apoptosis of AML cells as well as increased levels of proangiogenic Interleukin 8

Cited by 62 publications

References 26 publications

Release of angiopoietin-1 by primary human acute myelogenous leukemia cells is associated with mutations of nucleophosmin, increased by bone marrow stromal cells and possibly antagonized by high systemic angiopoietin-2 levels

Release of angiopoietin-1 by primary human acute myelogenous leukemia cells is associated with mutations of nucleophosmin, increased by bone marrow stromal cells and possibly antagonized by high systemic angiopoietin-2 levels

The proteasome inhibitors bortezomib and PR‐171 have antiproliferative and proapoptotic effects on primary human acute myeloid leukaemia cells

Bone Marrow

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