Expression of tumor-suppressor genes interferon regulatory factor 1 and death-associated protein kinase in primitive acute myelogenous leukemia cells

Guzmán, Mónica L.; Upchurch, Donna; Grimes, Barry; Howard, Dianna S.; Rizzieri, David A.; Luger, Selina M.; Phillips, Gordon L.; Jordan, Craig T.

doi:10.1182/blood.v97.7.2177

Cited by 51 publications

(38 citation statements)

References 20 publications

(19 reference statements)

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“…51 Many recent reports aimed to define the characteristics of leukemic progenitor cells present in AML have shown the constitutive activation of transcription factors like STATs 52 or NF-kB, 9 as well as aberrant expression of tumor suppressor genes IRF1 and DAPK. 8,53 Data reported in this paper indicate the herg gene as the first K + channel enco-ding gene which is constitutively up-regulated in AML blasts, being completely turned off either in mature myeloid cells and in resting CD34 + cells.…”

Section: Discussionmentioning

confidence: 72%

“…[2][3][4] While the phenotype of leukemic stem cells has been defined, [2][3][4][5][6][7] it is emerging that primitive AML cells aberrantly express several set of genes, particularly those involved in the regulation of cell cycle progression and apoptosis. 8,9 Hence, the comparison between the pattern of genes expressed in normal vs leukemic progenitors is now regarded as a fundamental topic in the understanding of the biological features of malignant transformation leading to AML development.…”

Section: Introductionmentioning

confidence: 99%

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HERG potassium channels are constitutively expressed in primary human acute myeloid leukemias and regulate cell proliferation of normal and leukemic hemopoietic progenitors

et al. 2002

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An important target in the understanding of the pathogenesis of acute myeloid leukemias (AML) relies on deciphering the molecular features of normal and leukemic hemopoietic progenitors. In particular, the analysis of the mechanisms involved in the regulation of cell proliferation is decisive for the establishment of new targeted therapies. To gain further insight into this topic we report herein a novel approach by analyzing the role of HERG K + channels in the regulation of hemopoietic cell proliferation. These channels, encoded by the human ether-agò -gò -related gene (herg), belong to a family of K + channels, whose role in oncogenesis has been recently demonstrated. We report here that herg is switched off in normal peripheral blood mononuclear cells (PBMNC) as well as in circulating CD34 + cells, however, it is rapidly turned on in the latter upon induction of the mitotic cycle. Moreover, herg appears to be constitutively activated in leukemic cell lines as well as in the majority of circulating blasts from primary AML. Evidence is also provided that HERG channel activity regulates cell proliferation in stimulated CD34 + as well as in blast cells from AML patients. These results open new perspectives on the pathogenetic role of HERG K + channels in leukemias.

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Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

HERG potassium channels are constitutively expressed in primary human acute myeloid leukemias and regulate cell proliferation of normal and leukemic hemopoietic progenitors

et al. 2002

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“…22 Interestingly, these experiments showed that two tumor suppressor genes, interferon regulatory factor 1 (IRF-1), and death associated protein kinase (DAPK) were consistently up-regulated in primitive AML cells, but not in CD34…”

Section: Molecular Biologymentioning

confidence: 99%

Unique molecular and cellular features of acute myelogenous leukemia stem cells

Jordan

2002

Leukemia

110

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It is well known in the field of acute myelogenous leukemia (AML) that many different translocations and genetic aberrancies are found with the various forms of the disease. Indeed, specific translocations are often associated with disease subtypes that manifest themselves through the accumulation of immature myeloid cells at varying stages of differentiation. Moreover, the differentiation state of myeloid blast populations has been utilized as a means of categorizing different AML subtypes (French, American, British, or FAB classification system). Thus, the notion that AML is a family of related but distinct diseases is a common view. Interestingly, however, studies in recent years that have formalized the concept of a leukemic stem cell (LSC) have also begun to define shared developmental, cellular and molecular features amongst the malignant stem cells that give rise to different AML subtypes. Moreover, some of these conserved features appear to be unique to the leukemia stem/progenitor cell population, and are not found in normal hematopoietic stem cells (HSCs). This article will summarize data emerging from the study of LSCs and suggest how distinct molecular and cellular characteristics of the LSC population may provide new opportunities for AML therapy.

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“…For example, two recent studies have described aberrant expression of tumor suppressor genes and the transcription factor NF-kB in primitive AML but not normal hematopoietic cells. 25,26 Several interesting advances have also been made for chronic myelogenous leukemia (CML), which will be reviewed in the 'New dogma' section by Connie Eaves and her colleagues. Perhaps most importantly, it has been shown that primitive CML cells appear to possess autocrine cytokine activity that may be central to their cell cycle activation and differentiation.…”

Section: Figurementioning

confidence: 99%