AML1 is overexpressed in patients with myeloproliferative neoplasms and mediates JAK2V617F-independent overexpression of NF-E2

Wang, Wei; Schwemmers, Sven; Hexner, Elizabeth O.; Pahl, Heike L.

doi:10.1182/blood-2009-11-254664

Cited by 46 publications

(41 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…14 In ET and PMF, NF-E2 overexpression is independent of the presence or absence of the JAK2 V617F mutation. 15 Moreover, in a murine model, elevated NF-E2 levels cause an MPN phenotype. 16 Here we test the hypothesis that immunohistochemical staining for NF-E2 can be used to distinguish ET from PMF and that this distinction can aid in the classification of MPN, unclassifiable (MPN,U) patients.…”

Section: Introductionmentioning

confidence: 99%

Subcellular mislocalization of the transcription factor NF-E2 in erythroid cells discriminates prefibrotic primary myelofibrosis from essential thrombocythemia

Aumann

Frey

May

et al. 2013

Blood

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

Subcellular mislocalization of the transcription factor NF-E2 in erythroid cells discriminates prefibrotic primary myelofibrosis from essential thrombocythemia

Aumann

Frey

May

et al. 2013

Blood

Self Cite

View full text Add to dashboard Cite

show abstract

“…Overexpression of NFE2 has been reported in patients with all three subtypes of myeloproliferative neoplasms, independent of the presence or absence of the JAK2V617F mutation [142,143]. When expressed ectopically in BM cells, NFE2 also influences earlier stages of MK differentiation and allegedly enhances in vivo platelet production.…”

Section: Nfe2mentioning

confidence: 99%

Transcriptional Regulation of Platelet Formation: Harnessing the Complexity for Efficient Platelet Production In Vitro

Tijssen

Moreau

Ghevaert

2016

Molecular and Cellular Biology of Platelet Formation

View full text Add to dashboard Cite

It is now common knowledge that specific repertoires of transcription factors (TFs) determine a cell's protein content and thereby its phenotype. The expression of a given TF is not necessarily cell specific, and many TFs play a pivotal role in several different cell types. For example, TAL1, FLI1, RUNX1, ERG and GATA2 are important regulators of stem cells, but also play a vital role in megakaryopoiesis. Although the megakaryocyte (MK) and its closest relative, the red blood cell, share key TFs like GATA1 and NFE2, the bifurcation between the two lineages has been associated with pairs of TFs that act as a toggle switch (such as FLI1 and KLF1). This chapter will summarise the current knowledge of key transcriptional regulators of MK differentiation and how some of these TFs, despite being expressed in several cell types, can impose MK cell identity. Since the discovery of TPO in 1994, our knowledge of MK biology and differentiation has increased exponentially, but we still lack a deep understanding of what triggers the transition from MK growth and maturation to proplatelet formation. We describe how some well-known TFs control the expression of proteins that play a pivotal role in the dramatic cytoplasmic and cytoskeletal events that accompany proplatelet formation. Finally, we show how TFs can be harnessed in a powerful way to produce MKs and, potentially, platelets in vitro for future clinical applications.

show abstract

“…We used three different hematopoietic cell lines, HEL, SET2 and UKE1, the latter two of which are derived form MPN patients. All three cell lines express high levels of NF-E2 9 and secrete high levels of IL-8 when transduced with an empty control vector or a vector expressing a scrambled, inactive shRNA ( Figure 3A-C). Transduction with the NF-E2 shRNA significantly reduces IL-8 protein secretion in all three lines ( Figure 3A-C).…”

Section: Nf-e2 Expression Modulates Il-8 Protein Levelsmentioning

confidence: 99%

“…8,9 NF-E2 is a tissue specific transcription factor expressed in hematopoietic stem cells as well as in the myeloid, erythroid and megakaryocytic lineage. 10 NF-E2 overexpression in polycythemia vera (PV), ET and PMF is independent of the presence or absence of the JAK2 V617F mutation.…”

Section: Introductionmentioning

confidence: 99%

“…10 NF-E2 overexpression in polycythemia vera (PV), ET and PMF is independent of the presence or absence of the JAK2 V617F mutation. 8,9 In a murine model, NF-E2 overexpression causes an MPN phenotype including thrombocytosis, leukocytosis, erythropoietin (Epo)-independent colony formation, characteristic bone marrow histology, expansion of stem-and progenitor compartments, and spontaneous transformation to acute myeloid leukemia. 11 This observation establishes a role for aberrant NF-E2 expression in the pathophysiology of MPN.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Transcription factor nuclear factor erythroid-2 mediates expression of the cytokine interleukin 8, a known predictor of inferior outcome in patients with myeloproliferative neoplasms

et al. 2013

View full text Add to dashboard Cite

ARTICLES 1073 Myeloproliferative DisordersThe transcription factor nuclear factor erythroid-2 is over-expressed in patients with myeloproliferative neoplasms irrespective of the presence of the JAK2 V617F mutation. Our transgenic mouse model over-expressing nuclear factor erythroid-2, which recapitulates many features of myeloproliferative neoplasms including transformation to acute myeloid leukemia, clearly implicates this transcription factor in the pathophysiology of myeloproliferative neoplasms. Because the targets mediating nuclear factor erythroid-2 effects are not well characterized, we conducted microarray analysis of CD34 + cells lentivirally transduced to over-express nuclear factor erythroid-2 or to silence this transcription factor via shRNA, in order to identify novel target genes. Here, we report that the cytokine interleukin 8 is a novel target gene. Nuclear factor erythroid-2 directly binds the interleukin 8 promoter in vivo, and these binding sites are required for promoter activity. Serum levels of interleukin 8 are known to be elevated in both polycythemia vera and primary myelofibrosis patients. Recently, increased interleukin 8 levels have been shown to be predictive of inferior survival in primary myelofibrosis patients in multivariate analysis. Therefore, one of the mechanisms by which nuclear factor erythroid-2 contributes to myeloproliferative neoplasm pathology may be increased interleukin 8 expression.Transcription factor nuclear factor erythroid-2 mediates expression of the cytokine interleukin 8, a known predictor of inferior outcome in patients with myeloproliferative neoplasms

show abstract

AML1 is overexpressed in patients with myeloproliferative neoplasms and mediates JAK2V617F-independent overexpression of NF-E2

Cited by 46 publications

References 49 publications

Subcellular mislocalization of the transcription factor NF-E2 in erythroid cells discriminates prefibrotic primary myelofibrosis from essential thrombocythemia

Subcellular mislocalization of the transcription factor NF-E2 in erythroid cells discriminates prefibrotic primary myelofibrosis from essential thrombocythemia

Transcriptional Regulation of Platelet Formation: Harnessing the Complexity for Efficient Platelet Production In Vitro

Transcription factor nuclear factor erythroid-2 mediates expression of the cytokine interleukin 8, a known predictor of inferior outcome in patients with myeloproliferative neoplasms

Contact Info

Product

Resources

About