Differential expression of transforming growth factor-beta, basic fibroblast growth factor, and their receptors in CD34+ hematopoietic progenitor cells from patients with myelofibrosis and myeloid metaplasia

Bousse-Kerdiles, MC Le; Chevillard, Sylvie; Charpentier, Agnès; Romquin, N.; Clay, Denis; Smadja-Joffe, Florence; Perreten, Vincent; Dupriez, Brigitte; Demory, Jean Loup; Jasmin, C; Martyré, Marie‐Claire

doi:10.1182/blood.v88.12.4534.bloodjournal88124534

Cited by 112 publications

(45 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, studies of haemopoietic pathologies and leukaemias have shown abnormalities in TGFb signalling activity in both early myeloid leukaemia [19], and lymphocytic leukaemia [20]. In CML, the oncogenic Bcr-Abl fusion protein drives haemopoietic cell transformation, and also sustains a rare cohort of quiescent Bcr-Abl+ haemopoietic progenitor cells that persist throughout the CML-CP [21].…”

Section: Discussionmentioning

confidence: 99%

Upregulation of the TGFβ signalling pathway by Bcr‐Abl: Implications for haemopoietic cell growth and chronic myeloid leukaemia

et al. 2007

View full text Add to dashboard Cite

Chronic myeloid leukaemia (CML) is a myeloproliferative disorder characterized by uncontrolled growth of progenitor cells expressing the tyrosine kinase fusion gene product, Bcr-Abl. At present, little is known regarding how TGFb, and downstream Smad transcription factors, influence CML cell proliferation in the context of Bcr-Abl expression. Here we show that ectopic Bcr-Abl expression dramatically increases TGFb/ Smad-dependent transcriptional activity in Cosl cells, and that this may be due to enhancement of Smad promoter activity. Bcr-Abl expressing TF-1 myeloid cells are more potently growth arrested by TGFb compared to the parental TF-1 cell line. Additionally, growth of Bcr-Abl-expressing CD34+ cells from chronic phase CML patients is inhibited by TGFb and, interestingly, treatment of a non-proliferating CD34+ CML cell subpopulation with the TGFb kinase inhibitor SB431542 enhanced cell death mediated by the Bcr-Abl inhibitor imatinib. Our data suggest that the expression of Bcr-Abl leads to hyper-responsiveness of myeloid cells to TGFb, and we hypothesise that this novel cross-regulatory mechanism might play an important role in maintaining the transformed progenitor cell population in CML.

show abstract

Section: Discussionmentioning

confidence: 99%

Upregulation of the TGFβ signalling pathway by Bcr‐Abl: Implications for haemopoietic cell growth and chronic myeloid leukaemia

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Receptors for FGFs have been found on K562 cells (Allouche, 1995;Liuzzo and Moscatelli, 1996) and on CD34 hematopoietic progenitor cells (Berardi et al, 1995;Le Bousse-Kerdil Á es et al, 1996;Testa et al, 1996;Burger et al, 1998Burger et al, , 1999 and direct effects of bFGF have been shown on progenitor cell proliferation (Gabbianelli et al, 1990;Bruno et al, 1993;Gabrilove et al, 1994;Allouche, 1995;Berardi et al, 1995). These direct effects are signi®cantly less than those noted when bFGF is added to stromal based hematopoietic cultures Quito et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…bFGF is produced by K562 cells (Allouche, 1995), chronic lymphocytic leukemia cells (Menzel et al, 1996), hairy cell leukemia cells (Gruber et al, 1999) and normal hematopoietic and bone marrow stromal cells (Brunner et al, 1993;Peoples et al, 1995). Increased expression of both bFGF and the FGF type I and type II receptors has been found in CD34 cells from patients who have myelo®brosis with myeloid metaplasia as compared with cells from normal donors (Le Bousse-Kerdil Á es et al, 1996). Signi®cantly elevated levels of bFGF were found in cells from patients with high-risk and intermediate-risk chronic lymphocytic leukemia compared to the levels in cells from those individuals with low-risk disease (Menzel et al, 1996).…”

Section: Bfgf Inhibits Erythroid Differentiationmentioning

confidence: 99%

“…bFGF also promotes myeloblast proliferation and inhibits the terminal differentiation of skeletal muscle cells (Clegg et al, 1987;Olwin and Rapraeger, 1992). 1995; Berardi et al, 1995;Le Bousse-Kerdil Á es et al, 1996;Liuzzo and Moscatelli, 1996;Testa et al, 1996;Burger et al, 1998Burger et al, , 1999. bFGF prevents the transforming growth factor-b (TGF-b)-mediated increase in hemoglobin production by K562 cells (Burger et al, 1994).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Basic fibroblast growth factor modulates the expression of glycophorin A and c‐kit and inhibits erythroid differentiation in K562 cells

Burger¹,

Lukey²,

Coetzee³

et al. 2001

Journal Cellular Physiology

View full text Add to dashboard Cite

Basic fibroblast growth factor (bFGF) is produced by bone marrow stromal cells as well as by normal and leukemic hematopoietic cells. In this study, we examine the direct effects of bFGF on erythroid differentiation in K562 cells in order to determine whether bFGF can promote the expression of a primitive phenotype. Low levels of bFGF inhibited erythroid differentiation as evidenced by decreased expression of glycophorin A and increased expression of c-kit. bFGF also increased both the numbers and the sizes of colonies of K562 cells in soft agar assays. The addition of TGF-beta to these cells induced erythroid differentiation which resulted in an increase in glycophorin A and a decrease in c-kit. The simultaneous addition of bFGF and TGF-beta to K562 cells prevented both the TGF-beta-mediated increase in glycophorin A expression and the decrease in c-kit expression associated with erythroid differentiation. bFGF antagonised the TGF-beta-mediated promotion of erythroid differentiation in K562 cells in a dose dependent manner and these two cytokines counteracted each other on an approximately molar basis. These results indicate that bFGF alone increases expression of c-kit and promotes a primitive phenotype in K562 cells. In addition, bFGF counteracts the effects of differentiation-inducing cytokines, such as TGF-beta, on hematopoietic cells. It is therefore possible that enhanced production of bFGF by leukemic cells could contribute to their neoplastic phenotype by opposing the effects of negative regulators or cytokines that induce differentiation.

show abstract

“…Expression of bFGF and its receptors has been shown in a few other haematological malignancies. In myelofibrosis, an increased production of bFGF has been linked to the fibrotic process (Le Bousse-Kerdiles et al, 1996), whereas serum bFGF levels correlate with clinical stage in B-CLL (Menzel et al, 1996;Aguayo et al, 2000b;Molica, 2001).…”

Section: P-valuementioning

confidence: 99%

A morphometric study of bone marrow angiogenesis in hairy cell leukaemia with clinicopathological correlations

Korkolopoulou

Gribabis²,

Kavantzas³

et al. 2003

Br J Haematol

View full text Add to dashboard Cite

Summary. Bone marrow angiogenesis has recently been implicated in the pathophysiology and course of various haematological malignancies. Little is known, however, about the significance of this phenomenon in hairy cell leukaemia (HCL). We evaluated various morphometric characteristics of microvessels, highlighted by means of anti-CD34 immunohistochemistry, in the bone marrow of 44 patients with typical HCL, before and after treatment with interferon-a (IFN-a). Overall, bone marrow from 103 HCL patients and 20 controls was examined. Microvessel density (MVD) and several size-and shape-related parameters were quantified in the region of most intense vascularization using image analysis. MVD, size-related parameters and the percentage of branching microvessels were higher in HCL than in controls. Likewise, perimeter counts were higher in partial/non-responders than in complete responders.Achievement of complete response was accompanied by smaller calibre microvessels. IFN-a induced a decrease in MVD and branching values in cases with diffuse marrow involvement. In univariate analysis, progression-free survival was adversely affected by MVD, branching and major axis length. Multivariate analysis indicated that MVD/ branching independently affected progression-free survival and the likelihood of complete response. Our data suggest that the generation of bone marrow microvessels indicated an increased risk of progression and IFN-a treatment failure in HCL. Furthermore, the prognostic significance of angiogenesis requires the concomitant assessment of MVD and the complexity of the microvascular network.

show abstract

Differential expression of transforming growth factor-beta, basic fibroblast growth factor, and their receptors in CD34+ hematopoietic progenitor cells from patients with myelofibrosis and myeloid metaplasia

Cited by 112 publications

References 47 publications

Upregulation of the TGFβ signalling pathway by Bcr‐Abl: Implications for haemopoietic cell growth and chronic myeloid leukaemia

Upregulation of the TGFβ signalling pathway by Bcr‐Abl: Implications for haemopoietic cell growth and chronic myeloid leukaemia

Basic fibroblast growth factor modulates the expression of glycophorin A and c‐kit and inhibits erythroid differentiation in K562 cells

A morphometric study of bone marrow angiogenesis in hairy cell leukaemia with clinicopathological correlations

Contact Info

Product

Resources

About