Changing bone marrow micro‐environment during development of acute myeloid leukaemia in rats

Mortensen, Børge Thing; Jensen, Peter Østrup; Helledie, Niels; Iversen, Per Ole; Ralfkiær, Elisabeth; Larsen, Jørgen K.; Madsen, Mads T.

doi:10.1046/j.1365-2141.1998.00801.x

Cited by 62 publications

(58 citation statements)

References 15 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prominent examples include differentiation induction therapy, developed from preliminary studies with cyclic adenosine monophosphate (cAMP) inducing cholera toxin in the BNML and BNML-cholera toxin-resistant models, 161,268 269 circuitously leading to the clinical studies of agents such as theophylline 273 (cAMP induction/stabilisation), Gemtuzumab ozogamicin 274 (conjugated mAb) and granulocyte colony-stimulating factor 275 (G-CSF-cytokine). These results and the application of the BNML rat model in more recent work pertaining to angiogenesis and microenvironmental modifications by Iversen et al [276][277][278][279] rationalise continued interest in this model.…”

Section: Mrd Detection and Treatment In Bnmlmentioning

confidence: 77%

Animal models of acute myelogenous leukaemia – development, application and future perspectives

2005

View full text Add to dashboard Cite

From the early inception of the transplant models through to contemporary genetic and xenograft models, evolution of murine leukaemic model systems have been critical to our general comprehension and treatment of cancer, and, more specifically, disease states such as acute myelogenous leukaemia (AML). However, even with modern advances in therapeutics and molecular diagnostics, the majority of AML patients die from their disease. Thus, in the absence of definitive in vitro models which precisely recapitulate the in vivo setting of human AMLs and failure of significant numbers of new drugs late in clinical trials, it is essential that murine AML models are developed to exploit more specific, targeted therapeutics. While various model systems are described and discussed in the literature from initial transplant models such as BNML and spontaneous murine leukaemia virus models, to the more definitive genetic and clinically significant NOD/SCID xenograft models, there exists no single compendium which directly assesses, reviews or compares the relevance of these models. Thus, the function of this article is to provide clinicians and experimentalists a chronological, comprehensive appraisal of all AML model systems, critical discussion on the elucidation of their roles in our understanding of AML and consideration to their efficacy in the development of AML chemotherapeutics.

show abstract

Section: Mrd Detection and Treatment In Bnmlmentioning

confidence: 77%

Animal models of acute myelogenous leukaemia – development, application and future perspectives

2005

View full text Add to dashboard Cite

show abstract

“…Leukemia is cancer of blood cells, and it has been shown that acidic microenvironment is a key feature of exponentially growing cells in bone marrow (Mortensen et al 1998). Especially, acute leukemia is a rapidly progressing disease that results in the accumulation of immature, abnormal cells in the marrow and blood.…”

Section: Introductionmentioning

confidence: 99%

Low-pH-induced apoptosis: role of endoplasmic reticulum stress-induced calcium permeability and mitochondria-dependent signaling

Sharma

Kaur

Bhatnagar

et al. 2015

Cell Stress and Chaperones

View full text Add to dashboard Cite

The acidic microenvironment around tumor cells is a major determinant in cancer growth, metabolism, and metastasis. However, its role in cancer physiology is still not clearly understood. In the present investigation, an attempt has been made to explore the effect of acidic environment on physiology of cancer cells. Exposure of Raji cells to extracellular acidic environment was associated with enhanced cytosolic calcium level and endoplasmic reticulum stress response. X-box binding protein 1 (XBP1) splicing, CCAAT/ enhancer-binding protein homologous protein (CHOP), and glucose-regulated protein 78 kDa (GRP78) upregulation suggested endoplasmic reticulum stress generation. On the other hand, real-time-based upregulation of Bax gene expression and flow cytometric analysis of cytochrome c release as well as enhanced active caspase-3 further confirmed mitochondrion-mediated events leading to induction of apoptosis. The expression of TP53 and p21 was upregulated. These observations collectively strongly suggest that both endoplasmic reticulum stress-mediated calcium release and Bax targeting might be altering mitochondrion membrane potential which in turn could induce secondary apoptotic signals; subsequently, endoplasmic reticulum stress can also lead to nuclear localization of Nuclear factor-κB (NF-κB) which in turn favors p53 mediated apoptotic signals.

show abstract

“…13,14 We have used this BNML model extensively to study the bone marrow microenvironment during progression of the leukemic process. [15][16][17] Given these recent observations that angiogenesis might play a role in progression of leukemia, the aim of the present study was to examine if treatment with the anti-angiogenic compounds endostatin and/or PI-88 could arrest the expansion of malignant cell populations in our two experimental models of human myeloid leukemia, the JMML mice and the BNML rats.…”

Section: Introductionmentioning

confidence: 99%

Inhibitors of angiogenesis selectively reduce the malignant cell load in rodent models of human myeloid leukemias

2002

View full text Add to dashboard Cite

Angiogenesis is essential for growth and metastasis of solid tumors and probably also for hematological malignancies. Angiogenic inhibitors, like endostatin (ES) and PI-88, retard cancer growth. We tested these in mice with juvenile myelomonocytic leukemia (JMML), and in rats with acute myeloid leukemia (BNML). Eight weeks after transplantation and with a continuous drug treatment for the last 4 weeks, the leukemic cell mass decreased from almost 90% of all bone marrow cells to about 15 and 45% with ES, to about 35 and 55% with PI-88, and to about 10 and 25% with ES + PI-88 in the leukemic mice and rats, respectively. The numbers of normal human bone marrow cells transplanted into mice were unchanged by the treatments. The microvessel density in leukemic animals given ES or PI-88 was 10-50% of that in untreated animals. Notably, simultaneous treatment with ES and PI-88 led to a reduction of about 95% in JMML mice and 85% in BNML rats. In vitro proliferation of either JMML or BNML cells was not significantly altered by either drug, demonstrating the selectivity of ES and PI-88 as angiogenic inhibitors. In conclusion, anti-angiogenic therapy may be a valuable adjunct to conventional treatment of leukemia.

show abstract

Changing bone marrow micro‐environment during development of acute myeloid leukaemia in rats

Cited by 62 publications

References 15 publications

Animal models of acute myelogenous leukaemia – development, application and future perspectives

Animal models of acute myelogenous leukaemia – development, application and future perspectives

Low-pH-induced apoptosis: role of endoplasmic reticulum stress-induced calcium permeability and mitochondria-dependent signaling

Inhibitors of angiogenesis selectively reduce the malignant cell load in rodent models of human myeloid leukemias

Contact Info

Product

Resources

About