Common alterations in gene expression and increased proliferation in recurrent acute myeloid leukemia

Staber, Philipp B.; Linkesch, Werner; Zauner, Dorothea; Beham‐Schmid, Christine; Godballe, Christian; Schauer, Silvia; Sill, Heinz; Höefler, Gerald

doi:10.1038/sj.onc.1207192

Cited by 65 publications

(45 citation statements)

References 45 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This result was further confirmed by MEK/MAPK assay, the activation of which has been shown to correlate with cell proliferation. 30 Here also, there is no difference in the extent of ERK1/2 phosphorylation upon stimulation of both cells with either the epidermal growth factor (EGF) or the hepatic growth factor (HGF) (Fig. 3b).…”

Section: Fut1 Does Not Affect Cell Proliferation or Adhesion To Extramentioning

confidence: 79%

Introducing α(1,2)‐linked fucose into hepatocarcinoma cells inhibits vasculogenesis and tumor growth

Mathieu¹,

Gerolami²,

Luis³

et al. 2007

Intl Journal of Cancer

View full text Add to dashboard Cite

The glycoantigen sialyl-Lewis x (sLex) and its isomer sialy-Lewis a (sLea) are frequently associated with advanced states of cancer and metastasis. In a previous work, we have shown that hepatocarcinoma cells (HCC) HepG2 interact with the endothelial Eselectin exclusively through sLe x oligosaccharides, the synthesis of which could be completely prevented by the a(1,2)-fucosyltransferase-I (FUT1), thus resulting in a strong inhibition of adhesion and rolling on activated endothelial cells. The purpose of the present study was to evaluate the impact of inhibiting sLex synthesis and the subsequent E-selectin adhesion, on HCC tumor growth in nude mice. Four weeks after subcutaneous transplantation of cells, no FUT1-derived tumor could be detected, whereas 75% of control animals developed large size tumor nodules. Between the 4th and the 8th week postinoculation, 33% tumors arose from FUT1-transduced cells but showed a slow growth (nodule volumes less than 500 mm 3 ), while more than 50% of control tumors reached volumes between 1,500 and 3,000 mm 3 . Several parameters were examined, including cell division and proliferation, apoptosis, adhesion to extracellular matrix components and angiogenesis/vasculogenesis. We provide evidence that among all, vasculogenesis was the most clearly affected by FUT1 expression, suggesting that tumor angiomorphogenesis may, at least partly, depend on Eselectin-mediated interaction between HCC and endothelial cells, the inhibition of which remarkably retards tumor growth. ' 2007 Wiley-Liss, Inc.Key words: a(1,2)-fucosyltransferase-I; E-selectin; sialyl-Lewis; antitumor; vasculogenesisThe sialyl-Lewis antigens (sLex and sLea) are blood grouprelated antigens naturally expressed on leukocytes to initiate leukocyte-endothelium interaction mediated by the cytokine-inducible endothelial adhesion molecule E-selectin. 1,2 In addition to this physiological role in inflammation, sialyl-Lewis antigens are also considered as tumor markers expressed on many cancer cells and therefore, they are thought to be involved in metastasis by initiating tumor cell-endothelium adhesion. 3 Indeed, the expression of sialyl-Lewis antigens on carcinoma cells is frequently associated with advanced states of cancer and a statistically relevant relationship has been established between the postoperative prognosis of patients and the degree of expression of sialyl-Lewis antigens on cancer tissues. 3 Besides, several lines of evidence from selectin-deficient mice studies pointed out the contribution of selectins in facilitating tumor growth and progression. 4,5 In particular, E-selectin and its sLex-containing glycoconjugate ligands have been shown to be involved in the essential events of tumor angiogenesis, 6-9 including the fact that coinjection of tumor cells expressing high level of sLe x together with endothelial cells constitutively expressing E-selectin, has been found to promote tumor angiogenesis and growth. 10 We have recently succeeded in strongly blocking the expression of sLex on digestive cancer cells...

show abstract

Section: Fut1 Does Not Affect Cell Proliferation or Adhesion To Extramentioning

confidence: 79%

Introducing α(1,2)‐linked fucose into hepatocarcinoma cells inhibits vasculogenesis and tumor growth

Mathieu¹,

Gerolami²,

Luis³

et al. 2007

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…31 It is unclear as to the effects of loss of EHD3 in myeloid cells, but it is interesting to note various studies that show an involvement of transferrin and/or the transferrin receptor levels in the pathogenesis of AMLs. 32,33 Furthermore, the elucidation of other cargo contained within EHD3-associated endosomes may provide crucial insights into the pathogenesis of various AMLs.…”

Section: Discussionmentioning

confidence: 99%

Discovery of epigenetically silenced genes in acute myeloid leukemias

Raynaud

Tung

et al. 2007

Leukemia

View full text Add to dashboard Cite

The demethylating 5-aza-2 0 deoxycytidine (DAC) and the histone deacetylase inhibitor (HDACi) suberoyl anilide bishydroxamide (SAHA) possess potent antitumorigenic properties in myeloid disorders. However, the transcriptome alterations mediated by these drugs are poorly understood. We analyzed the transcriptional effects of DAC and SAHA in the AML cell line KG-1. Microarray analyses revealed 76 genes expressed in normal CD34 þ cells, absent in KG-1 cells but whose expression was induced after drug treatment. A total of 39 of these genes harbored CpG islands in their promoters. We examined the expression level of these genes in 120 AML patient samples representing diverse karyotpyes. Gas2l1, tfIIs, ehd3, enolase 2, mx1, dral, astml and pxdn were diminished across all AML karyotypes examined. Ehd3 was methylated in 63% of AML patients examined. This methylation was lost upon complete remission, and not observed in normal CD34 þ cells. CD34 þ cells expressed ehd3 at approximately 10-fold higher levels than AML samples. Another highlighted gene, a-catenin, is located at q31 of chromosome 5. Analyses of 29 5q-AML/ myelodysplastic syndrome (MDS) samples revealed marked decreases in expression of a-catenin, compared to non-5q-MDS samples (6.679-fold). However, no methylation was detected, suggesting indirect effects of these drugs on the expression of a-catenin.

show abstract

“…Abnormalities of chromosome 5 are common aberrations in acute myeloid leukemia (AML), with del(5q) the most frequent (66,67). There is also literature, which shows that EGR-1 was related to recurrent disease following high-dose chemotherapy (68). Nevertheless, EGR1 haploinsufficiency alone in vivo does not lead to expansion of HSCs or abnormalities in adult hematopoiesis.…”

Section: Pathogenesis Mechanism Of Aml By Egr1mentioning

confidence: 99%