Acute myeloid leukemia cells are protected from spontaneous and drug-induced apoptosis by direct contact with a human bone marrow stromal cell line (HS-5)

Garrido, Sara; Appelbaum, Frederick R.; Willman, Cheryl L.; Banker, Deborah E.

doi:10.1016/s0301-472x(01)00612-9

Cited by 204 publications

(195 citation statements)

References 33 publications

Supporting

Mentioning

175

Contrasting

Unclassified

Order By: Relevance

“…This inhibition may be further increased by similar inhibitory effects on fibroblast subsets and the release of direct inhibitory mediators like IL-1RA (IL-1␤/IL-1RA ratio Ͻ1.00 is usually maintained even in fibroblast/AML cell cocultures). Taken together with previous results (Ryningen, unpublished), 5,7,22,34,37 we therefore suggest that nonleukemic stromal cells may be important in disease development in AML patients through several mechanisms, including enhancement of leukemic hematopoiesis, stimulation of bone marrow angiogenesis and reduced stimulation of remaining normal hematopoiesis.…”

Section: Discussionsupporting

confidence: 87%

“…[3][4][5][6][7][8][9][10][11][12][13][15][16][17] The molecular bidirectional crosstalk with stromal cells appears to support AML blast proliferation, [3][4][5][6][7][8][9]16,20,22 and our own prior studies demonstrated that both fibroblast cell lines HFL1 and Hs27, the osteoblastic sarcoma cell lines Cal72 and SJSA-1 and normal osteoblasts 33,34 can increase AML blast proliferation as well as release of proangiogenic IL-8 by native human AML cells. Fibroblasts also have an additional antiapoptotic effect, 22 and this effect is observed both with Hs27 and HFL1 fibroblasts (Ryningen, unpublished). Thus, the fibroblast and osteoblast cell lines included in our present study support leukemic hematopoiesis through several mechanisms.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

In vitro effects of native human acute myelogenous leukemia blasts on fibroblasts and osteoblasts

Glenjen

Ersvær

Ryningen

et al. 2004

Intl Journal of Cancer

View full text Add to dashboard Cite

Bone marrow stromal cells constitute a heterogeneous population, and in the present study we investigated intercellular crosstalk via release of soluble mediators between native human AML blasts and fibroblasts/osteoblasts. Coculture of nonleukemic stromal cells and AML blasts separated by a semipermeable membrane decreased proliferation of the fibroblast line HFL1, and the inhibition was maintained when HFL1 and AML cells were cultured in direct contact. A similar inhibitory effect was observed for osteoblastic sarcoma cell lines (Cal72, SJSA-1) and normal osteoblasts. GM-CSF was released by both nonleukemic cells and a subset of AML blast populations, and increased levels of GM-CSF were detected in AML cocultures with fibroblasts and osteoblastic sarcoma cells when testing AML cell populations with constitutive GM-CSF release. Furthermore, constitutive IL-1␤ secretion by AML blasts was detected only for a subset of patients, whereas relatively high levels of IL-1RA were observed for all patients; coculture of AML blasts with HFL1 fibroblasts and osteoblastic sarcoma cells increased IL-1␤ levels for patients with constitutive IL-1␤ secretion, whereas IL-1RA levels were slightly decreased but still generally higher than IL-1␤ levels (tested only for HFL1 fibroblasts). The bidirectional crosstalk between AML blasts and stromal cells with increased release of AML growth factors may be important in leukemogenesis, whereas the decreased stromal cell proliferation combined with the persistent release of IL-1RA may in addition inhibit remaining normal hematopoiesis and thereby contribute to bone marrow failure in AML.

show abstract

Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

In vitro effects of native human acute myelogenous leukemia blasts on fibroblasts and osteoblasts

Glenjen

Ersvær

Ryningen

et al. 2004

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Bone marrow samples were cocultured with HS5 cells as a feeder layer (Garrido et al, 2001), which maintained the viability of the leukemic cells for several days (data not shown). Although Kasumi-1 cells are very sensitive to DEP, these leukemic blasts were much less susceptible to even 5.0 nM DEP, showing no decrease in viability up to 16 h after drug treatment (as judged by Trypan blue exclusion, data not shown).…”

Section: Cells Was Immunoprecipitated Using Anti-runx1-n and Detectedmentioning

confidence: 99%

Histone deacetylase inhibitors induce the degradation of the t(8;21) fusion oncoprotein

et al. 2006

View full text Add to dashboard Cite

The t(8;21) chromosomal translocation that generates the fusion oncoprotein RUNX1-ETO predominates in leukemia patients of the French-American-British (FAB) class M2 subtype. The oncoprotein has the capacity to promote expansion of hematopoietic stem/progenitor cells and induces leukemia in association with other genetic alterations. Here, we show that RUNX1-ETO undergoes degradation in response to treatment with histone deacetylase inhibitors, one of which, depsipeptide (DEP), is currently undergoing phase II clinical testing in a variety of malignancies. These compounds induce turnover of RUNX1-ETO without affecting the stability of RUNX1-ETO partner proteins. In addition, RUNX1-ETO physically interacts with heat shock protein 90 (HSP90). DEP treatment interrupts the association of RUNX1-ETO with HSP90 and induces proteasomal degradation of RUNX1-ETO. DEP and the HSP90 antagonist 17-allylamino-geldanamycin (17-AAG) both triggered RUNX1-ETO degradation, but without any additive or cooperative effects. These findings may stimulate the development of more rational and effective approaches for treating t(8;21) patients using histone deacetylase inhibitors or HSP90 inhibitors.

show abstract

“…1,2 Moreover, the marrow is considered to be the site of origin for minimal residual disease (MRD), as adhesion to BM stroma cells and signaling through their secreted elements induce AML cells resistance to cytotoxic drugs. 3,4 Marrow-derived stromal cells constitutively secrete the chemokine stromal cell-derived factor-1 (SDF-1) (also named CXCL-12), which is the only chemoattractant for hematopoietic progenitor cells, that is so far proved as significant. 5,6 In previous studies, our group and others, showed that the SDF-1 and its receptor CXCR4 interaction is essential for both normal and leukemic hematopoietic cell migration in vivo.…”

Section: Introductionmentioning

confidence: 99%

The CXCR4 antagonist AMD3100 impairs survival of human AML cells and induces their differentiation

et al. 2008

View full text Add to dashboard Cite

The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, participate in the retention of acute myeloblastic leukemia (AML) cells within the bone marrow microenvironment and their release into the circulation. AML cells also constitutively express SDF-1-dependent elastase, which regulates their migration and proliferation. To study the molecular events and genes regulated by the SDF-1/CXCR4 axis and elastase in AML cells, we examined gene expression profiles of the AML cell line, U937, under treatment with a neutralizing anti-CXCR4 antibody or elastase inhibitor, as compared with non-treated cells, using DNA microarray technology. Unsupervised hierarchical clustering analysis demonstrated similar gene expression profiles of anti-CXCR4 antibody or elastase inhibitor-treated cells, as compared with control. Pathway and functional analysis showed a greater tendency toward differentiation in cells under either one of both treatment modalities. Thus given, we further analyzed the effects of CXCR4 inhibition on AML cell growth and differentiation using the antagonist AMD3100. AMD3100 arrested proliferation in AML cell lines and triggered changes that mimicked differentiation, including morphological changes and the expression of myeloid differentiation antigens. Inhibition of elastase also triggered the differentiation of AML cells. Our study defines a new role for the SDF-1/CXCR4 axis in the regulation of leukemic cell survival and differentiation.

show abstract

Acute myeloid leukemia cells are protected from spontaneous and drug-induced apoptosis by direct contact with a human bone marrow stromal cell line (HS-5)

Cited by 204 publications

References 33 publications

In vitro effects of native human acute myelogenous leukemia blasts on fibroblasts and osteoblasts

In vitro effects of native human acute myelogenous leukemia blasts on fibroblasts and osteoblasts

Histone deacetylase inhibitors induce the degradation of the t(8;21) fusion oncoprotein

The CXCR4 antagonist AMD3100 impairs survival of human AML cells and induces their differentiation

Contact Info

Product

Resources

About