SET-NUP214 fusion in acute myeloid leukemia- and T-cell acute lymphoblastic leukemia-derived cell lines

Quentmeier, Hilmar; Schneider, Björn; Röhrs, Sonja; Romani, Julia; Zaborski, Margarete; MacLeod, Roderick A.F.; Drexler, Hans G.

doi:10.1186/1756-8722-2-3

Cited by 45 publications

(40 citation statements)

References 13 publications

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“…Lastly, the screen identified SET, a known epigenetic silencing factor that appears to function by blocking acetylation of histones 50 . A SET-NUP214 translocation has been identified in both AML and ALL 51 . Whether the putative epigenetic silencing roles for these eight factors are related to the described gene aberrations remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Human factors and pathways essential for mediating epigenetic gene silencing

et al. 2014

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Cellular identity in both normal and disease processes is determined by programmed epigenetic activation or silencing of specific gene subsets. Here, we have used human cells harboring epigenetically silent GFP-reporter genes to perform a genome-wide siRNA knockdown screen for the identification of cellular factors that are required to maintain epigenetic gene silencing. This unbiased screen interrogated 21,121 genes, and we identified and validated a set of 128 protein factors. This set showed enrichment for functional categories, and protein-protein interactions. Among this set were known epigenetic silencing factors, factors with no previously identified role in epigenetic gene silencing, as well as unstudied factors. The set included non-nuclear factors, for example, components of the integrin-adhesome. A key finding was that the E1 and E2 enzymes of the small ubiquitin-like modifier (SUMO) pathway (SAE1, SAE2/UBA2, UBC9/UBE2I) are essential for maintenance of epigenetic silencing. This work provides the first genome-wide functional view of human factors that mediate epigenetic gene silencing. The screen output identifies novel epigenetic factors, networks, and mechanisms, and provides a set of candidate targets for epigenetic therapy and cellular reprogramming.

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Section: Discussionmentioning

confidence: 99%

Human factors and pathways essential for mediating epigenetic gene silencing

et al. 2014

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“…It has been rarely reported in AML and acute undifferentiated leukemia, but recurrently in T-cell acute lymphoblastic leukemia [148]. The SET-NUP214 fusion protein retains the acidic tail of SET and the CC domain and GLFG repeat domain of NUP214 [63,149]. The protein binds at HOXA promoters, facilitating the recruitment of the H3K79 methyltransferase DOT1L, which, in turn, activates transcription of specific members of the HOXA cluster (Table 1) [63].…”

Section: • • Nup214 Fusion Genesmentioning

confidence: 99%

Hox gene Dysregulation in Acute Myeloid Leukemia

et al. 2014

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In humans, class I homeobox genes (HOX genes) are distributed in four clusters. Upstream regulators include transcriptional activators and members of the CDX family of transcription factors. HOX genes encode proteins and need cofactor interactions, to increase their specificity and selectivity. HOX genes contribute to the organization and regulation of hematopoiesis by controlling the balance between proliferation and differentiation. Changes in HOX gene expression can be associated with chromosomal rearrangements generating fusion genes, such as those involving MLL and NUP98, or molecular defects, such as mutations in NPM1 and CEBPA for example. Several miRNAs are involved in the control of HOX gene expression and their expression correlates with HOX gene dysregulation. HOX genes dysregulation is a dominant mechanism of leukemic transformation. A better knowledge of their target genes and the mechanisms by which their dysregulated expression contributes to leukemogenesis could lead to the development of new drugs.

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“…Samples were prepared as described by Quentmeier et al 17 We used the nuclear extract kit (Active Motif; La Hulpe, Belgium) to separate cytoplasmic and nuclear proteins. Bands on nitrocellulose membranes were visualized with the biotin/streptavidin-horseradish peroxidase system (GE Healthcare; Little Chalfont, UK) in combination with Renaissance Western Blot Chemoluminescence Reagent (Perkin Elmer; Waltham, MA, USA).…”

Section: Western Blot Analysismentioning

confidence: 99%

BCL6 - regulated by AhR/ARNT and wild-type MEF2B - drives expression of germinal center markers MYBL1 and LMO2

et al. 2015

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Knock-down experimentsTransfection with short interfering (si) RNA oligonucleotides was performed as described elsewhere.14 Gene-specific siRNA oligonucleotides and AllStars negative control siRNA were obtained from Qiagen (Hilden, Germany). The siRNA (80 pmol) were transfected into 1x10 6 cells by electroporation using an EPI-2500 impulse generator (Fischer, Heidelberg, Germany) at 350 V for 10 ms. Treated cells were harvested after 20 h.

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SET-NUP214 fusion in acute myeloid leukemia- and T-cell acute lymphoblastic leukemia-derived cell lines

Cited by 45 publications

References 13 publications

Human factors and pathways essential for mediating epigenetic gene silencing

Human factors and pathways essential for mediating epigenetic gene silencing

Hox gene Dysregulation in Acute Myeloid Leukemia

BCL6 - regulated by AhR/ARNT and wild-type MEF2B - drives expression of germinal center markers MYBL1 and LMO2

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