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

Quentmeier H, Schneider B, Röhrs S, Romani J, Zaborski M, Macleod RA, Drexler HG - J Hematol Oncol (2009)

Bottom Line: Quantitative genomic PCR also confirmed loss of genomic material between SET and NUP214 in both cell lines.Of special note is that the formation of the SET exon 7/NUP214 exon 18 gene transcript requires alternative splicing as the SET breakpoint is located downstream of the stop codon in exon 8.The cell lines are promising model systems for SET-NUP214 studies and should facilitate investigating cellular functions of the the SET-NUP214 protein.

View Article: PubMed Central - HTML - PubMed

Affiliation: DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany. hqu@dsmz.de

ABSTRACT

Background: SET-NUP214 fusion resulting from a recurrent cryptic deletion, del(9)(q34.11q34.13) has recently been described in T-cell acute lymphoblastic leukemia (T-ALL) and in one case of acute myeloid leukemia (AML). The fusion protein appears to promote elevated expression of HOXA cluster genes in T-ALL and may contribute to the pathogenesis of the disease. We screened a panel of ALL and AML cell lines for SET-NUP214 expression to find model systems that might help to elucidate the cellular function of this fusion gene.

Results: Of 141 human leukemia/lymphoma cell lines tested, only the T-ALL cell line LOUCY and the AML cell line MEGAL expressed the SET(TAF-Ibeta)-NUP214 fusion gene transcript. RT-PCR analysis specifically recognizing the alternative first exons of the two TAF-I isoforms revealed that the cell lines also expressed TAF-Ialpha-NUP214 mRNA. Results of fluorescence in situ hybridization (FISH) and array-based copy number analysis were both consistent with del(9)(q34.11q34.13) as described. Quantitative genomic PCR also confirmed loss of genomic material between SET and NUP214 in both cell lines. Genomic sequencing localized the breakpoints of the SET gene to regions downstream of the stop codon and to NUP214 intron 17/18 in both LOUCY and MEGAL cells. Both cell lines expressed the 140 kDa SET-NUP214 fusion protein.

Conclusion: Cell lines LOUCY and MEGAL express the recently described SET-NUP214 fusion gene. Of special note is that the formation of the SET exon 7/NUP214 exon 18 gene transcript requires alternative splicing as the SET breakpoint is located downstream of the stop codon in exon 8. The cell lines are promising model systems for SET-NUP214 studies and should facilitate investigating cellular functions of the the SET-NUP214 protein.

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SET-NUP214 protein expression. Western blot analysis with Ab raised against the N-terminal region of SET and against the C-terminal region of NUP214. Cell lines LOUCY and MEGAL expressed the 140 kDa SET-NUP214 fusion protein and a 240 kDa protein marked with an asterisk, detected by both antibodies. No alternative splice forms were detected that would explain two SET-NUP214 size variants.
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Figure 5: SET-NUP214 protein expression. Western blot analysis with Ab raised against the N-terminal region of SET and against the C-terminal region of NUP214. Cell lines LOUCY and MEGAL expressed the 140 kDa SET-NUP214 fusion protein and a 240 kDa protein marked with an asterisk, detected by both antibodies. No alternative splice forms were detected that would explain two SET-NUP214 size variants.

Mentions: As previously reported for LOUCY, also cell line MEGAL expressed the SET-NUP214 fusion protein with a molecular weight of about 140 kDa (Fig. 5) [4].


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

Quentmeier H, Schneider B, Röhrs S, Romani J, Zaborski M, Macleod RA, Drexler HG - J Hematol Oncol (2009)

SET-NUP214 protein expression. Western blot analysis with Ab raised against the N-terminal region of SET and against the C-terminal region of NUP214. Cell lines LOUCY and MEGAL expressed the 140 kDa SET-NUP214 fusion protein and a 240 kDa protein marked with an asterisk, detected by both antibodies. No alternative splice forms were detected that would explain two SET-NUP214 size variants.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2636835&req=5

Figure 5: SET-NUP214 protein expression. Western blot analysis with Ab raised against the N-terminal region of SET and against the C-terminal region of NUP214. Cell lines LOUCY and MEGAL expressed the 140 kDa SET-NUP214 fusion protein and a 240 kDa protein marked with an asterisk, detected by both antibodies. No alternative splice forms were detected that would explain two SET-NUP214 size variants.
Mentions: As previously reported for LOUCY, also cell line MEGAL expressed the SET-NUP214 fusion protein with a molecular weight of about 140 kDa (Fig. 5) [4].

Bottom Line: Quantitative genomic PCR also confirmed loss of genomic material between SET and NUP214 in both cell lines.Of special note is that the formation of the SET exon 7/NUP214 exon 18 gene transcript requires alternative splicing as the SET breakpoint is located downstream of the stop codon in exon 8.The cell lines are promising model systems for SET-NUP214 studies and should facilitate investigating cellular functions of the the SET-NUP214 protein.

View Article: PubMed Central - HTML - PubMed

Affiliation: DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany. hqu@dsmz.de

ABSTRACT

Background: SET-NUP214 fusion resulting from a recurrent cryptic deletion, del(9)(q34.11q34.13) has recently been described in T-cell acute lymphoblastic leukemia (T-ALL) and in one case of acute myeloid leukemia (AML). The fusion protein appears to promote elevated expression of HOXA cluster genes in T-ALL and may contribute to the pathogenesis of the disease. We screened a panel of ALL and AML cell lines for SET-NUP214 expression to find model systems that might help to elucidate the cellular function of this fusion gene.

Results: Of 141 human leukemia/lymphoma cell lines tested, only the T-ALL cell line LOUCY and the AML cell line MEGAL expressed the SET(TAF-Ibeta)-NUP214 fusion gene transcript. RT-PCR analysis specifically recognizing the alternative first exons of the two TAF-I isoforms revealed that the cell lines also expressed TAF-Ialpha-NUP214 mRNA. Results of fluorescence in situ hybridization (FISH) and array-based copy number analysis were both consistent with del(9)(q34.11q34.13) as described. Quantitative genomic PCR also confirmed loss of genomic material between SET and NUP214 in both cell lines. Genomic sequencing localized the breakpoints of the SET gene to regions downstream of the stop codon and to NUP214 intron 17/18 in both LOUCY and MEGAL cells. Both cell lines expressed the 140 kDa SET-NUP214 fusion protein.

Conclusion: Cell lines LOUCY and MEGAL express the recently described SET-NUP214 fusion gene. Of special note is that the formation of the SET exon 7/NUP214 exon 18 gene transcript requires alternative splicing as the SET breakpoint is located downstream of the stop codon in exon 8. The cell lines are promising model systems for SET-NUP214 studies and should facilitate investigating cellular functions of the the SET-NUP214 protein.

Show MeSH
Related in: MedlinePlus