Cancer Genetics and Cytogenetics 201 (2010) 73e80

Molecular characterization of alternative SET-NUP214 fusiontranscripts in a case of acute undifferentiated leukemia

Juwon Kima, Sang-Guk Leea, Jaewoo Songa, Soo Jeong Kimb, Sun Young Rhab,c,Kyung-A Leea, Tae Sung Parkd,1,*, Jong Rak Choia,1,*

aDepartment of Laboratory Medicine, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, KoreabDepartment of Internal Medicine, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu Seoul 120-752, Korea

cCancer Metastasis Research Center, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu Seoul 120-752, KoreadDepartment of Laboratory Medicine, School of Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-702, Korea

Received 20 January 2010; received in revised form 24 April 2010; accepted 18 May 2010

Abstract Cryptic deletions are occasionally reported in h

* Corresponding a

E-mail address:

ac (J.R. Choi).1 Both authors co

ered senior author.

0165-4608/$ - see fro

doi:10.1016/j.cancerg

ematologic malignancies. The SET-NUP214 fusiongene has been rarely reported in acute myeloid leukemia, acute undifferentiated leukemia, andrecurrently in T-cell acute lymphoblastic leukemia. The fusion product is generated by a submicro-scopic deletion in the vicinity of 9q34. Herein we present a novel case of acute undifferentiatedleukemia with SET-NUP214 rearrangement due to the cryptic deletion of the 9q34 region producingtwo different types of fusion transcripts by alternative splicing and molecular characterization of thefusion transcripts by fluorescence in situ hybridization, reverse transcriptaseepolymerase chainreaction, and array comparative genomic hybridization analyses. � 2010 Elsevier Inc. All rightsreserved.

1. Introduction

Cryptic or submicroscopic deletions generating chromo-somal translocation have occasionally been described inhematologic malignancies, the most commonly encoun-tered chromosome abnormalities of which are del(1)(p32)(TAL1 gene deletion), del(4)(q12) (FIP1L1-PDGFRA),cryptic 11q23 deletions (MLL-LARG or MLL-CBL rear-rangement), and t(9;9)(q34;q34) or del(9)(q34.11q34.13)(SET-NUP214 rearrangement). The SET-NUP214 rear-rangement can result from either chromosomal transloca-tion t(9;9)(q34;q34) [1] or a recurrent deletion, del(9)(q34.11q34.13) [2]. The SET-NUP214 was first describedin an acute undifferentiated leukemia (AUL) patient asa reciprocal translocation t(9;9) [1,3], and it was followedby one case in acute myeloid leukemia (AML) [4]. Later,three cases of T-cell leukemia patients [2] having del(9)(q34.11q34.13) were reported. Recently, Gorello et al.reported seven more cases of SET-NUP214-positive

uthor. Tel.:þ82-2-2228-2445; fax:þ82-2-313-0956.

153jesus@hanmail.net (T.S. Park) or cjr0606@yuhs.

ntributed equally to this work and both are consid-

nt matter � 2010 Elsevier Inc. All rights reserved.

encyto.2010.05.010

T-cell acute lymphoblastic leukemia (T-ALL); accordingto the report, the estimated incidence was 4.6% amongT-ALLs [5].

The NUP214 (aka CAN) mapping at chromosome 9q34,is a phenylalanine glycine repeat nucleoporin residing inthe cytoplasmic face of nucleoporin complex [6] that isimplicated in the nucleocytoplasmic transport includingmRNA import and export [7,8] and is required forhCRM1-dependent nuclear protein export [9,10]. NUP214is reported as being essential during development [7], andincreasing evidence points to the importance of the genein the leukemogenesis [3,6]. SET (aka TAF1), one of itspartner genes in the translocation, was reported as aputative oncogene that plays a part in transcription bymodulating chromatin organization [11]. It is a componentof the inhibitor of histone acetylation and transcriptionalactivation (INHAT) [11,12], and it was identified as apotent and specific inhibitor of protein phosphatase2A [13].

Here we present a novel case of AUL with SET-NUP214rearrangement due to the submicroscopic deletion of the9q34 region producing two different types of fusion tran-scripts by alternative splicing. We also provide a review ofthe literature.

74 J. Kim et al. / Cancer Genetics and Cytogenetics 201 (2010) 73e80

2. Materials and methods

2.1. Case description

A 40-year-old Korean man with leukocytosis anda hemorrhoid was admitted to Severance Hospital of YonseiUniversity for further evaluation. An initial complete bloodcount showed a hemoglobin (Hb) level of 13.3 g/dL anda platelet count of 33 � 109/L with a white blood cell countof 53 � 109/L with 84% blasts, 2% neutrophils, 13%lymphocytes, and 1% monocytes. Results of a bone marrowbiopsy revealed a hypercellular marrow with markedlyincreased myeloblasts (95%), some of which showed anAuer rod, indicating AML (Fig. 1). A chromosomal studyof this patient showed a normal karyotype in the 20metaphase cells that were analyzed. According to the im-munophenotyping, bone marrow blasts lacked T-cell- ormyeloid-specific markers such as cCD3 (1.3%) and MPO,and they did not express B-cell-specific markers such ascCD22 (0.1%), cCD79a (2.6%), or CD19 (0%), suggestingan AUL. The blasts were positive for CD7 (95.6%), CD33(51.7%), CD117 (73.8%), and CD38 (94.8%).

The patient received cytosine arabinoside and idarubicinas an induction therapy and experienced remission accord-ing to hematologic parameters with a blast count of 0.2%.Although episodes of neutropenic fever, depression, andsuspected fungal infection occurred during subsequentchemotherapy, the patient was generally able to toleratetreatment. The patient was lost to follow-up shortly afterthe first complete remission had been achieved (Table 1).

2.2. Conventional cytogenetic analysis

Chromosomes were prepared from a 24-hour unstimu-lated bone marrow culture. Briefly, the bone marrow cellswere grown in RPMI 1640 (Sigma, Schnelldorf, Germany)supplemented with 20% fetal bovine serum (Gibco, GrandIsland, NY), bone marrow growth supplement (GenialGenetic Solutions, Runcorn, UK), and antibiotics (penicillinand streptomycin). The cultured cells were then exposed toColcemid for 20 minutes, followed by 30 minutes of

Fig. 1. Morphology of leukemic cells at diagnosis (original magnification, �1,00

fine chromatin pattern. (B) WrighteGiemsaestained bone marrow aspirate smear

inent nucleoli and distinct Auer rod indicated by a red arrowhead.

hypotonic treatment (KCl). A fixation procedure withethanol and acetic acid (2.5:1) was performed. Chromosomeswere analyzed by the GTG banding technique, and the karyo-types were described according to the 2009 InternationalSystem for Human Cytogenetic Nomenclature [14].

2.3. Flow cytometry

Immunophenotypes of the bone marrow cells wereanalyzed by three-color flow cytometry with CD45/sidescatter gating with Cytomics FC500 flow cytometer (Beck-man Coulter, Fullerton, CA). An expression of each CDantigen on the gated cells was examined by the monoclonalantibodies and defined as positive when at least 20% of thegated cells showed fluorescence above the backgroundcontrol staining.

2.4. Fluorescence in situ hybridization analysis

Fluorescence in situ hybridization (FISH) analysis wasperformed according to the manufacturer’s instructionswith commercially available FISH probes supplied byAbbott Molecular (Des Plaines, IL). We conducted FISHanalyses for the RUNX1-RUNX1T1 (LSI AML1-ETO dual-color, dual-fusion translocation probe), PML-RARA (LSIPML-RARA dual-color, dual-fusion translocation probe),CBFB (LSI CBFB dual-color, break-apart rearrangementprobe), MLL (LSI MLL dual-color, break-apart rearrange-ment probe) rearrangements, along with BCR-ABL1 (LSIBCR-ABL, dual-color, dual-fusion translocation probe). Atleast 300 interphase cells were scored for signal patternsof each probe with a fluorescence microscope. Cell imageswere captured by a computer-based imaging system (Meta-Systems, Altlussheim, Germany).

2.5. Multiplex reverse transcriptaseepolymerase chainreaction, cloning, and sequencing analyses

A multiplex reverse transcriptaseepolymerase chainreaction (RT-PCR) assay was performed with a Hemavisionkit (Bio-Rad Laboratories, Hercules, CA) as described

0). (A) Peripheral blood film showing large blasts with scant cytoplasm and

showing increased numbers of blasts with irregular large nuclei with prom-

Table 1

Clinical, immunophenotypic, and genetic features in SET-NUP214 positive cases

Patient Sex/Age

Immunophenotype

or leukemia type Karyotype FISH analysis results SET-NUP213 fusion transcripts Array CGH data Follow-up

Survival

(mo) Reference

1 M/19 y AUL 46,XY NA 50 SET exon7-NUP214 exon18 30 t(9;9)(q34;q34)no del(9)

(q34.11q34.13)

NA NA [1,2,22]

2 M/35 y AML, M4 46,XY del(9)(q34)/ABL1 50 SET intron7-NUP214 intron17 30 del(9)(q34.1) Allogeneic

PBSCT

4 [4]

3 F/15.3 mo Mature Not done del(9)(q34)/ABL1 50 SET exon7-NUP214 exon18 30 del(9)(q34.11q34.13) CR 83 [2]

4 F/17.1 mo Cortical Not done del(9)(q34)/ABL1 50 SET exon7-NUP214 exon18 30 del(9)(q34.11q34.14) CR 37 [2]

5 F/10.6 mo Mature Not done del(9)(q34)/ABL1 50 SET exon7-NUP214 exon18 30 del(9)(q34.11q34.15) CR 83 [2]

6 M/38 y Pre-T ALL 46,XY[15] del(9)(q34)/ABL1 50 SET exon7-NUP214 exon17 30 Not done CR,

allogeneic

BMT

29 [5]

7 M/19 y Pre-T ALL 46,XY[15] del(9)(q34)/ABL1;del(6)(q16)/

GRIK2;del(12p)/ETV6;

50 SET exon7-NUP214 exon18 30 Not done Relapse and

death

23 [5]

8 M/47 y Cortical Failed del(9)(q34)/ABL1 50 SET exon7-NUP214 exon18 30 Not done Refused

treatment

NA [5]

9 F/27 y Pre-T ALL Failed del(9)(q34)/ABL1;del(9)(p21)/

CDK2A-B;del(11)(p13)/

LMO2;del(11)(q14)/CALM;

50 SET exon7-NUP214 exon18 30 Not done Resistant to

treatment

and death

23 [5]

10 M/19 y Pro-T ALL Failed del(9)(q34)/

ABL1;del(12)(p13)/

ETV6;del(11)(p13)/LMO2;

del(11)(q14)/CALM;

50 SET exon7-NUP214 exon18 30 Not done CR, in

treatment

3 [5]

11 M/18 y Pre-T ALL Failed del(9)(q34)/ABL1;del(5)(q35)/

TLX3

NA Not done Relapse and

death

24 [5]

12 M/23 y Pre-T ALL 46,XY[12] del(9)(q34)/ABL1 NA Not done Relapse and

death

17 [5]

13 M/41 y AUL 46,XY[20] del(9)(q34)/ABL1 50 SET exon7-NUP214 exon17 3050

SET exon7-NUP214 exon18 30del(9)(q34.11q34.13)

del(9)(q22)

CR 7 Present

case

Abbreviations: FISH, fluorescence in situ hybridization; CGH, comparative genetic hybridization; AUL, acute undifferentiated leukemia; T, T cell; AML, acute myeloid leukemia; CR, complete remission;

NA, not available; BMT, bone marrow transplantation; PBSCT, peripheral blood stem cell transplantation.

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76 J. Kim et al. / Cancer Genetics and Cytogenetics 201 (2010) 73e80

previously [15]. The purified PCR product was inserted intothe pCR2.1-TOPO vector (Invitrogen, Carlsbad, CA) ac-cording to the manufacturer’s specifications. PlasmidDNA was prepared with the plasmid Mini kit (Qiagen, Hil-den, Germany). Sequencing was performed in both forwardand reverse directions with a BigDye Terminator v 3.1cycle sequencing kit (Applied Biosystems, Foster City,CA) on a DNA sequencer (310; Applied Biosystems).Sequence analysis was performed using the Ensembl data-base (http://www.ensembl.org/index.html).

2.6. Array comparative genomic hybridization

Array comparative genetic hybridization (CGH) analysiswas performed for chromosome 9 on the Agilent HumanCGH Microarray 2X105K (Agilent Technologies, PaloAlto, CA) following the manufacturer’s instructions.Briefly, 1.5 mg genomic DNA of the patient or referenceDNA was digested with enzymes at 37�C overnight andpurified to be labeled with Cy5-dUTP and Cy3-dUTP witha genomic DNA enzymatic labeling kit. The hybridizationmixture was denatured at 95�C for 3 minutes, preincubatedat 37�C for 30 minutes, and hybridized to the array for40 hours at 65�C in a rotating oven at 20 rpm. Fluorescentsignals were acquired with a microarray scanner runningfeature extraction software version 9.5.3.1 (Agilent Tech-nologies). Data were analyzed by CGH Analytics version4.8 (Agilent Technologies). In brief, an ADM-2 for aberra-tion detection algorithm (aberration detection threshold6.0) and moving average of 10 pt (pt 5 probe) was used

Fig. 2. Fluorescence in situ hybridization (FISH) analysis and multiplex rever

NUP214 fusion transcript. (A) Dual-color FISH analysis of patient with LSI BCloss of the ABL1 gene and the probe binding site on the right. (B) Master RT-

393 bp) in lane 7 as well as internal 911-bp control band in each lane. Lane M

Sequencing results of the band of 552 bp (top) confirmed the chimeric transcrip

17 at the 30 end, whereas the fusion product of 393 bp (bottom) was confirmed

for analysis with fuzzy zero correction and centralizationthreshold at 6. The copy number changes were defined byintervals of three or more adjacent probes with log2 ratios,suggestive of a deletion or duplication when compared withthe log2 ratios of adjacent probes.

3. Results

To identify any presence of translocation amongleukemic blasts, a FISH analysis was carried out, and FISHsignals from PML-RARA, AML1-ETO, CBFB, and MLLprobes (Abbott Molecular) were within reference ranges.However, by means of BCR-ABL dual-color, dual-fusiontranslocation probe, the presence of a monoallelic loss ofthe ABL gene indicated by an atypical signal showing onered signal and two green signals was detected in 318 inter-phase cells out of 381 cells, comprising 83% of the totalleukemic population (nuc ish(ABLx1,BCRx2)[318/381])(Fig. 2A). Multiplex RT-PCR analysis revealed the pres-ence of SET-NUP214 fusion transcript measuring 552 bpand 393 bp (Fig. 2B). The sequencing analysis confirmedthat the fusion product 552 bp was formed by adjoiningexon 7 of SET gene and exon 17 of NUP214 gene whileSET exon 7 at the 50 end fused with NUP214 exon 18 atthe 30 end to form the fusion transcript 393 bp.

These results prompted us to further confirm the submi-croscopic deletion. The detailed analysis of the array CGHconfirmed a breakpoint near the SET gene and one copyloss of genetic material, including an approximately 3-Mb

se transcriptaseepolymerase chain reaction (RT-PCR) detection of SET-

R-ABL dual-color, dual-fusion translocation probe showing a monoallelic

PCR results with a Hemavision kit showing positive bands (552 bp and

, 100-bp DNA ladder as a size marker; lanes 1e8, master PCR lanes. (C)

t, which consisted of SET exon 7 at the 50 end fused with NUP214 exon

as a transcript of SET exon 7 fused to exon 18 of NUP214 gene.

77J. Kim et al. / Cancer Genetics and Cytogenetics 201 (2010) 73e80

region involving 9q34.11 to 9q34.13 (Fig. 3A,B). ThePKN3 just downstream of SET gene, CRAT, ASS1, andABL1 genes, were found to be deleted (Fig. 3B); part ofthe raw data (log2 ratios) is presented in Table 2. Anotherlarge deletion in the same chromosome covering q21.13to q22.32 was detected.

4. Discussion

The t(6;9)(p23;q34) results from a fusion of DEK onchromosome 6 and NUP214 on chromosome 9 [1], whichis one of the specific subtypes of AML according to theWorld Health Organization 2008 classification character-ized by a poor prognosis and young age at onset [16].DEK-NUP214 rearrangement is detected in only about0.7e1.8% of AML patients [16]. Other than DEK, therehave been two other partner genes reported to form afusion transcript with NUP214. One is an ABL1 gene,which is well known to form fusion transcripts withBCR gene in leukemias; the other is a SET, which playsa critical role in chromatin binding and remodeling [1].

Fig. 3. (A) Ideogram of chromosome 9 and corresponding array comparative g

NUP214 genes. (B) Diagram representing the array CGH results showing poten

SET-NUP214 rearrangement has been found mostly inT-ALL, one case of AML, and one case of AUL (Table 1).

For our case, the blasts contained an Auer rod, which isalso presented in one third of DEK-NUP214 AMLs, andshowed leukocytosis in the peripheral blood. However,the blasts expressed neither T-cell-specific nor myeloid-specific markers in immunophenotyping analysis, leadingto the diagnosis of AUL. The SET-NUP214 fusion genehas been reported in AUL once as t(9;9)(q32;q34), similarto the fusion product formed by the del(9)(q34.11q34.13).It was later found that the first AUL patient did not havedel(9)(q34.11q34.13) and the fusion product was formedas the result of a balanced t(9;9)(q34;q34) [2]. In our case,the SET-NUP214 fusion product was due to the del(9)(q34.11q34.13), as proven by FISH, array CGH, and multi-plex RT-PCR. Two transcripts of different sizes were foundin the multiplex RT-PCR analysis (Fig. 2B). As expected,subsequent sequencing analysis of the band of 552 bpconfirmed the chimeric transcript that consisted of SETexon 7 at the 50 end fused with NUP214 exon 17 at the30 end, whereas the fusion product of 393 bp was confirmed

enetic hybridization (CGH) plots showing breakpoints involving SET and

tial breakpoint regions with del(9)(q34.11q34.13).

Table 2

Example of test to reference log2 ratio obtained from the tab view of array comparative genetic hybridization analysis

Probe name Start Stop Gene name Test to reference log2 ratio Results

A_16_P02183701 130896885 130896944 CRAT �1.1426075 Deletion

A_16_P32552533 130897668 130897712 CRAT �0.7348355 Deletion

A_16_P38884680 130898374 130898374 CRAT �0.07774253 Deletion

A_16_P02183705 130899292 130899336 CRAT �0.8265002 Deletion

A_16_P02183707 130900414 130900461 CRAT �0.6287502 Deletion

A_16_P18781467 130902149 130902199 CRAT �0.556896 Deletion

A_16_P38884692 130902716 130902760 CRAT �0.88889277 Deletion

A_16_P02183712 130904038 130904082 CRAT �0.6417613 Deletion

A_16_P02183715 130905131 130905189 CRAT �0.6329607 Deletion

A_16_P02183717 130905831 130905881 CRAT �1.0296313 Deletion

A_16_P18781481 130906499 130906549 CRAT �0.7900388 Deletion

A_16_P114689 130907364 130907423 CRAT �0.7890874 Deletion

A_18_P17015812 132579138 132579197 ABL1 �0.7692344 Deletion

A_14_P126295 132580095 132580154 ABL1 �0.9777634 Deletion

A_16_P18785321 132580786 132580845 ABL1 �0.63080835 Deletion

A_16_P18785324 132584357 132584416 ABL1 �1.0544555 Deletion

A_16_P18785325 132584911 132584970 ABL1 �0.5023234 Deletion

A_16_P38888818 132586244 132586303 ABL1 �1.2655654 Deletion

A_16_P18785328 132586941 132587000 ABL1 �0.9418446 Deletion

A_16_P18785331 132587980 132588039 ABL1 �0.89156926 Deletion

A_16_P38888825 132588829 132588888 ABL1 �0.81823456 Deletion

A_16_P18785336 132589588 132589647 ABL1 �0.8197707 Deletion

A_16_P18785338 132590218 132597215 ABL1 �0.77524793 Deletion

A_16_P18785339 132597156 132597775 ABL1 �0.8562757 Deletion

A_16_P18785350 132600636 132600694 ABL1 �0.6409694 Deletion

A_16_P18780627 130486114 130486173 SET 0.3241867 No change

A_16_P18780630 130486922 130486970 SET 0.14718536 No change

A_18_P26763918 130487769 130487813 SET 0.19254428 No change

A_16_P18780634 130488326 130488385 SET 0.3037917 No change

A_14_P133690 130489123 130489182 SET 0.05464329 No change

A_16_P38883696 130489765 130489817 SET 0.122575074 No change

A_16_P02183251 130490400 130490459 SET 0.08076021 No change

A_16_P02183253 130492060 130492104 SET 0.51981246 No change

A_18_P17013918 130492982 130493041 SET 0.40884146 No change

A_14_P130522 130493930 130493989 SET 0.20528686 No change

A_16_P18780652 130494666 130494725 SET 0.17813787 No change

A_16_P18784638 132311067 132311111 ASS1 �0.21618838 Deletion

A_18_P26766985 132311672 132311717 ASS1 �0.82516813 Deletion

A_16_P18784644 132312615 132312663 ASS1 �1.1037672 Deletion

A_16_P38888095 132313423 132313467 ASS1 �0.9832473 Deletion

A_18_P26767467 132314748 132314792 ASS1 �0.921877 Deletion

A_16_P02185500 132315262 132315306 ASS1 �0.93796384 Deletion

A_16_P02185502 132316084 132316128 ASS1 �0.6712148 Deletion

A_16_P02185504 132316677 132316727 ASS1 �0.5489476 Deletion

A_16_P18784657 132317658 132317704 ASS1 �0.59495175 Deletion

A_18_P26768902 132318268 132318317 ASS1 �0.8246424 Deletion

A_16_P02185510 132319139 132319194 ASS1 �1.273122 Deletion

A_16_P38883775 130514354 130514398 PKN3 �0.2796741 Deletion

A_16_P32549183 130515085 130515129 PKN3 �0.7313074 Deletion

A_16_P32549218 130515658 130515702 PKN3 �0.794245 Deletion

A_16_P18780711 130516985 130517044 PKN3 �0.7644001 Deletion

A_16_P32549288 130517482 130517528 PKN3 �0.94455767 Deletion

A_18_P17008541 130518799 130518846 PKN3 �0.23845072 Deletion

A_16_P32549327 130520452 130520503 PKN3 �0.87156916 Deletion

A_16_P02183293 130522081 130522126 PKN3 �0.81324816 Deletion

A_16_P17011443 130522961 130523020 PKN3 �0.57658374 Deletion

78 J. Kim et al. / Cancer Genetics and Cytogenetics 201 (2010) 73e80

as a transcript of SET exon 7 fused to exon 18 of NUP214gene (Fig. 2C). It thus indicates that the mRNA of SET-NUP214 is expressed by alternative splicing, which waspostulated by von Lindern et al. [3,17].

Another larger deletion covering q21.13 to q22.32 wasalso observed in array CGH and suspected in the conven-tional chromosome analysis. The large deletion doubtlesshad a considerable effect on leukemogenesis, and further

79J. Kim et al. / Cancer Genetics and Cytogenetics 201 (2010) 73e80

evaluation of the genes that lie in that region is necessary.The del(9)(q21.1q22.3) has been reported in cases of Ewingsarcoma, AML, and angioimmunoblastic lymphadenopathy[18e20], but the significance of deletion in this region hasnot yet been discussed. In regards to FISH results, therehave been five cases of precursor B-cell ALL [21] thatshowed a monoallelic loss of ABL1 signal without anyfusion signals, like our case, indicating a deletion of onecopy of the ABL1 gene, although it has not been unambig-uously proven at the molecular level. However, furtherinvestigation of the aberration by a more advanced tech-nique such as array CGH provided us with a more detailedview of the chromosomal aberration, showing the exactlocation of the deletion and the breakpoints created by thatdeletion. In cases of a single signal loss without any fusionproducts with a BCR-ABL1 FISH probe, further molecularworkup (RT-PCR or array CGH) is needed to learn whetherthe deletion includes any other genes besides ABL1 in thechromosome 9.

It has been shown that the overexpression of such fusiongenes caused a lethal effect in mice and cell lines, althoughthis finding is controversial [22]. Not only the leukemias butalso the solid tumors have shown an involvement of the SET-NUP214 fusion gene in its tumorigenesis [22]. In the contextof hematopoiesis, differentiation of erythroid, megakaryo-cytic, and B-cell lineages were impaired in SET-NUP214transgenic mice [23]. In fact, siRNA-mediated SET-NUP214 knockdown experiments inhibited HOXA geneexpression, which normally is restricted to the earliest stagesof differentiation, reduced cell proliferation and differentia-tion, leading to accumulation of undifferentiated cells [2].Intriguingly, SET-NUP214 fusion was present in most ofthe cells in our study, indicating that SET-NUP214 probablyis an early oncogenic event, as pointed out by Van Vlier-berghe et al. [2]. In addition, the phenotype of the cellsharboring the SET-NUP214 fusion gene was found to beimmature in the first reported case [3]. Thus, in order tounveil its role in leukemogenesis, additional studies willbe crucial to address the effect of SET-NUP214 in itsdownstream effectors or cell cycle regulators playing animportant role in the control of cell development and differ-entiation. The relationship between the development ofAUL and SET-NUP214 should be further elucidated.

In conclusion, we report a case of AUL harboring dele-tion of the 9q34 region resulting in the SET-NUP214 fusiongene. The accumulation of more cases would be helpful inunderstanding the prognosis of patients harboring suchaberration and in improving treatment strategies.

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