Skip to main content
SpringerLink
Log in

Identification of Fusion Transcripts in Leukеmic Cells by Whole-Transcriptome Sequencing

  • Genomics. Transcriptomics
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract

Genetic aberrations in leukemia often lead to the formation of expressed chimeric genes, which should be assessed for proper diagnosis and therapy. Modern methods of molecular diagnostic mainly allow to identify already known fusion genes. RNAseq is an efficient tool for identification of rare and novel chimeric transcripts. Here we present the results of the whole transcriptome analysis of bone marrow samples from five patients with acute myeloblastic leukemia and one, with myelodysplastic syndrome. The wholetranscriptome analysis was performed using Illumina/Solexa approach. We found rare or unknown chimeric transcripts including ETV6-MDS1, MN1-ETV6, OAZ1-PTMA, and MLLT10-GRIA4. Each of these transcripts was confirmed by RT-PCR and Sanger sequencing.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

AML:

acute myeloid leukemia

CN-AML:

cytogenetically normal AML

RT-PCR:

reverse transcription-polymerase chain reaction

AF9 (MLLT3):

super elongation complex subunit gene

AF10 (MLLT10):

mixed lineage leukemia, translocated to, 10

AML1 :

gene of acute myeloid leukemia protein 1

AMPA4 (alpha 4):

glutamate ionotropic receptor AMPA type subunit 4 gene

ASXL1 :

additional sex combs like 1 transcriptional regulator

CBFA2T3 :

CBFA2/RUNX1 translocation partner 3 gene

CBFB :

core-binding factor beta gene

CEBPA :

CCAAT/enhancer-binding protein alpha gene

DHH (desert hedgehog):

gene of the signal protein of Hedgehog family

DNMT3A :

DNA methyltransferase-3-alpha gene

ETO (eight twenty-one):

gene of translocation (8;21)

ETV6 (E-twentysix):

gene of specific variant 6 of E26 transformation family

EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit):

gene of histone-lysine-N-methyltransferase

FLT3 :

gene of fms related tyrosine kinase 3

GLIS2 :

GLIS family zinc finger 2 protein gene

GRIA4 :

glutamate ionotropic receptor AMPA-type subunit 4

RP1-170O19.22 :

gene of axonemal microtubule associated protein RP

GPR128 :

gene of the G protein-coupled receptor 128

HOXA10 :

homeobox A10 protein gene

IDH1 :

cytosolic isocitrate dehydrogenase (NADP(+)) 1 gene

IDH2 :

mitochondrial isocitrate dehydrogenase (NADP(+)) 2 gene

MDS1 :

myelodysplasia syndrome 1 gene

MLL :

mixed lineage leukemia gene

MN1 :

gene of transcriptional regulator, meningioma proto-oncogene

MYH11 :

gene of myosin heavy chain 11

NGS:

next-generation sequencing

NPM1 :

nucleophosmin gene

NUP98 :

nucleoporin 98

NUSAP1 :

nucleolar and spindle-associated protein 1 gene

OAZ1 :

ornithine decarboxylase antizyme 1 gene

PHF23 :

PHD finger protein 23 gene

PML :

promyelocytic leukemia gene

PTMA :

gene of prothymosin alpha

RARA1 :

gene of retinoic acid receptor alpha

RHEBL1 :

Ras homolog enriched in brain like 1 gene

SEPT6 :

gene of septin 6

TET2 :

tet-methylcytosine dioxygenase 2 gene

TFG :

TRK-fused gene

WDR6 :

WD repeat domain 6

References

  1. Creutzig U., Zimmermann M., Reinhardt D., et al. 2016. Changes in cytogenetics and molecular genetics in acute myeloid leukemia from childhood to adult age groups. Cancer. 122, 3821–3830.

    Article  CAS  PubMed  Google Scholar 

  2. Papaemmanuil E., Gerstung M., Bullinger L., et al. 2016. Genomic classification and prognosis in acute myeloid leukemia. N. Engl. J. Med. 374, 2209–2221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Marcucci G., Mrózek K., Ruppert A.S., et al. 2005. Prognostic factors and outcome of core binding factor acute myeloid leukemia patients with t(8;21) differ from those of patients with inv(16): A cancer and leukemia group B study. J. Clin. Oncol. 23, 5705–5717.

    Article  PubMed  Google Scholar 

  4. Marschalek R. 2011. Mechanisms of leukemogenesis by MLL fusion proteins. Br. J. Haematol. 152, 141–154.

    Article  CAS  PubMed  Google Scholar 

  5. Falini B., Mecucci C., Tiacci E., et al. 2005. GIMEMA Acute Leukemia Working Party. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N. Engl. J. Med. 352, 254–266.

    Article  CAS  PubMed  Google Scholar 

  6. Togni M., Masetti R., Pigazzi M., et al. 2015. Identification of the NUP98–PHF23 fusion gene in pediatric cytogenetically normal acute myeloid leukemia by wholetranscriptome sequencing. J. Hematol. Oncol. 8,69.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Masetti R., Pigazzi M., Togni M., et al. 2013. GBFA2T3–GLIS2 fusion transcript is a novel common feature in pediatric, cytogenetically normal AML, not restricted to FAB M7 subtype. Blood. 121, 3469–3472.

    Article  CAS  PubMed  Google Scholar 

  8. Masetti R., Togni M., Astolfi A., et al. 2013. DHH–RHEBL1 fusion transcript: A novel recurrent feature in the new landscape of pediatric CBFA2T3–GLIS2-positive acute myeloid leukemia. Oncotarget. 4, 1712–1720.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Yatsenko Y., Kalennik O., Maschan M., et al. 2013. NPM1, FLT3, and c-KIT mutations in pediatric acute myeloid leukemia in Russian population. J. Pediatr. Hematol. Oncol. 35, 100–108.

    Article  Google Scholar 

  10. Liang D.C., Liu H.C., Yang C.P., et al. 2013. Cooperating gene mutations in childhood acute myeloid leukemia with special reference on mutations of ASXL1, TET2, IDH1, IDH2, and DNMT3A. Blood. 121, 2988–2995.

    Article  CAS  PubMed  Google Scholar 

  11. Bolger A.M., Lohse M., Usadel B. 2014. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics. 30, 2114–2120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kim D., Pertea G., Trapnell C., et al. 2013. TopHat2: Accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 14, R36.

    Article  PubMed  PubMed Central  Google Scholar 

  13. McPherson A., Hormozdiari F., Zayed A., et al. 2011. deFuse: An algorithm for gene fusion discovery in tumor RNA-Seq data. PLoS Comput. Biol. 7, e1001138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Krzywinski M., Schein J., Birol I., et al. 2009. Circos: An information aesthetic for comparative genomics. Genome Res. 19, 1639–1645.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. De Braekeleer E., Douet-Guilbert N., Morel F., et al. 2012. ETV6 fusion genes in hematological malignancies: A review. Leuk. Res. 36, 945–961.

    Article  PubMed  Google Scholar 

  16. Kim Y.J., Yang J.J., Han Y., et al. 2017. A rare case of ETV6/MECOM rearrangement in therapy-related acute myeloid leukemia with t(3;12) and monosomy 7. Clin. Lab. 63, 415–418.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia

    A. Yu. Ikonnikova, A. V. Snezhkina, G. S. Krasnov, A. V. Kudryavtseva & T. V. Nasedkina

  2. Federal Research and Clinical Center of Pediatric Hematology, Oncology, and Immunology, Moscow, 119117, Russia

    Yu. I. Ammour & T. V. Nasedkina

Authors
  1. A. Yu. Ikonnikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu. I. Ammour
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. V. Snezhkina
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. S. Krasnov
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. V. Kudryavtseva
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T. V. Nasedkina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T. V. Nasedkina.

Additional information

Original Russian Text © A.Yu. Ikonnikova, Yu.I. Ammour, A.V. Snezhkina, G.S. Krasnov, A.V. Kudryavtseva, T.V. Nasedkina, 2018, published in Molekulyarnaya Biologiya, 2018, Vol. 52, No. 2, pp. 231–237.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ikonnikova, A.Y., Ammour, Y.I., Snezhkina, A.V. et al. Identification of Fusion Transcripts in Leukеmic Cells by Whole-Transcriptome Sequencing. Mol Biol 52, 200–205 (2018). https://doi.org/10.1134/S0026893318020048

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893318020048

Keywords

Search

Navigation