Limits...
Fusion of ZMYND8 and RELA genes in acute erythroid leukemia.

Panagopoulos I, Micci F, Thorsen J, Haugom L, Buechner J, Kerndrup G, Tierens A, Zeller B, Heim S - PLoS ONE (2013)

Bottom Line: Cytogenetic analysis of bone marrow (BM) cells showed a t(11;20)(p11;q11) translocation.RT-PCR and direct sequencing verified the presence of an in frame ZMYND8-RELA chimeric transcript.Fluorescence in situ hybridization showed that the ZMYND8-RELA was located on the p12 band of der(11); therefore a cytogenetically invisible pericentric inversion in chromosome 11 must have taken place besides the translocation.

View Article: PubMed Central - PubMed

Affiliation: Section for Cancer Cytogenetics, Institute for Medical Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. ioannis.panagopoulos@rr-research.no

ABSTRACT
Acute erythroid leukemia was diagnosed in a 4-month-old boy. Cytogenetic analysis of bone marrow (BM) cells showed a t(11;20)(p11;q11) translocation. RNA extracted from the BM was sequenced and analyzed for fusion transcripts using the software FusionMap. A ZMYND8-RELA fusion was ranked first. RT-PCR and direct sequencing verified the presence of an in frame ZMYND8-RELA chimeric transcript. Fluorescence in situ hybridization showed that the ZMYND8-RELA was located on the p12 band of der(11); therefore a cytogenetically invisible pericentric inversion in chromosome 11 must have taken place besides the translocation. The putative ZMYND8-RELA fusion protein contains the Zinc-PHD finger domain, a bromodomain, a PWWP domain, a MYND type of zinc finger of ZMYND8, and the entire RELA protein, indicating that it might act leukemogenically by influencing several cellular processes including the NF-kappa-B pathway.

Show MeSH

Related in: MedlinePlus

Diagram showing the domains of ZMYND8, RELA and the fusion ZMYND8-RELA protein.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3646816&req=5

pone-0063663-g003: Diagram showing the domains of ZMYND8, RELA and the fusion ZMYND8-RELA protein.

Mentions: The ZMYND8 protein contains a Zinc-PHD finger domain, a bromodomain, a PWWP domain, and a MYND type of zinc finger (Figure 3, www.ensembl.org). It functions as a receptor for activated C-kinase (RACK) protein [13] but is also a cutaneous T-cell lymphoma-associated antigen (http://www.ncbi.nlm.nih.gov/gene/23613). The RELA protein is related to c-Rel and its oncogenic avian derivative v-Rel protein, contains an RHD domain (Figure 3), and forms complexes with the most abundant form NFKB1 of the transcription factor NF-kappa-B [14] (http://www.ncbi.nlm.nih.gov/gene/5970). NF-kappa-B plays a key role in inflammatory and innate immune responses and its role in oncogenesis is being investigated [15], [16]. NF-kappa-B was found to be constitutively activated in CD34+ AML cells but not in the normal CD34+ hematopoietic cells [17], [18]. Supershift experiments identified both NFKB1 and RELA proteins in the myeloid blast nucleous and the presence of NFKB1/RELA heterodimer as well as NFKB1 and RELA homodimers [17], [18]. Constitutive activation of NFKB in AML cells may be caused by various mechanisms such as alterated kinase activity, receptor overexpression autocrine cytokine production, and viral infections [19]. So far, no structural aberrations or locus amplification of RELA have been found [20]. The present study is therefore the first in which a rearrangement of RELA was detected and perhaps the ZMYND8-RELA fusion gene might be another novel mechanism of constitutive activation of NFKB in AML cells since the RELA gene is under control of the ZMYND8 promoter.


Fusion of ZMYND8 and RELA genes in acute erythroid leukemia.

Panagopoulos I, Micci F, Thorsen J, Haugom L, Buechner J, Kerndrup G, Tierens A, Zeller B, Heim S - PLoS ONE (2013)

Diagram showing the domains of ZMYND8, RELA and the fusion ZMYND8-RELA protein.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3646816&req=5

pone-0063663-g003: Diagram showing the domains of ZMYND8, RELA and the fusion ZMYND8-RELA protein.
Mentions: The ZMYND8 protein contains a Zinc-PHD finger domain, a bromodomain, a PWWP domain, and a MYND type of zinc finger (Figure 3, www.ensembl.org). It functions as a receptor for activated C-kinase (RACK) protein [13] but is also a cutaneous T-cell lymphoma-associated antigen (http://www.ncbi.nlm.nih.gov/gene/23613). The RELA protein is related to c-Rel and its oncogenic avian derivative v-Rel protein, contains an RHD domain (Figure 3), and forms complexes with the most abundant form NFKB1 of the transcription factor NF-kappa-B [14] (http://www.ncbi.nlm.nih.gov/gene/5970). NF-kappa-B plays a key role in inflammatory and innate immune responses and its role in oncogenesis is being investigated [15], [16]. NF-kappa-B was found to be constitutively activated in CD34+ AML cells but not in the normal CD34+ hematopoietic cells [17], [18]. Supershift experiments identified both NFKB1 and RELA proteins in the myeloid blast nucleous and the presence of NFKB1/RELA heterodimer as well as NFKB1 and RELA homodimers [17], [18]. Constitutive activation of NFKB in AML cells may be caused by various mechanisms such as alterated kinase activity, receptor overexpression autocrine cytokine production, and viral infections [19]. So far, no structural aberrations or locus amplification of RELA have been found [20]. The present study is therefore the first in which a rearrangement of RELA was detected and perhaps the ZMYND8-RELA fusion gene might be another novel mechanism of constitutive activation of NFKB in AML cells since the RELA gene is under control of the ZMYND8 promoter.

Bottom Line: Cytogenetic analysis of bone marrow (BM) cells showed a t(11;20)(p11;q11) translocation.RT-PCR and direct sequencing verified the presence of an in frame ZMYND8-RELA chimeric transcript.Fluorescence in situ hybridization showed that the ZMYND8-RELA was located on the p12 band of der(11); therefore a cytogenetically invisible pericentric inversion in chromosome 11 must have taken place besides the translocation.

View Article: PubMed Central - PubMed

Affiliation: Section for Cancer Cytogenetics, Institute for Medical Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. ioannis.panagopoulos@rr-research.no

ABSTRACT
Acute erythroid leukemia was diagnosed in a 4-month-old boy. Cytogenetic analysis of bone marrow (BM) cells showed a t(11;20)(p11;q11) translocation. RNA extracted from the BM was sequenced and analyzed for fusion transcripts using the software FusionMap. A ZMYND8-RELA fusion was ranked first. RT-PCR and direct sequencing verified the presence of an in frame ZMYND8-RELA chimeric transcript. Fluorescence in situ hybridization showed that the ZMYND8-RELA was located on the p12 band of der(11); therefore a cytogenetically invisible pericentric inversion in chromosome 11 must have taken place besides the translocation. The putative ZMYND8-RELA fusion protein contains the Zinc-PHD finger domain, a bromodomain, a PWWP domain, a MYND type of zinc finger of ZMYND8, and the entire RELA protein, indicating that it might act leukemogenically by influencing several cellular processes including the NF-kappa-B pathway.

Show MeSH
Related in: MedlinePlus