Skip to main content

Advertisement

Log in

PAX5 alteration-associated gene-expression signatures in B-cell acute lymphoblastic leukemia

International Journal of Hematology Aims and scope Submit manuscript

Abstract

The paired box domain gene 5 (PAX5) is frequently altered in both childhood and adult B-cell acute lymphoblastic leukemia, and takes part in leukemogenesis. We analyzed data from the database of Gene Expression Omnibus (accession number: GSE11877) using bioinformatical and statistical methods. The results showed that cases of PAX5 alteration can cluster using unsupervised clustering algorithms, and one gene, zinc and ring finger 1 (ZNRF1), was characterized and validated by quantitative RT-PCR. ZNRF1 may be associated with leukemogenesis of ALL with PAX5 alteration.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

References

  1. Saarinen-Pihkala UM, Heilmann C, Winiarski J, Glomstein A, Abrahamsson J, Arvidson J, et al. Pathways through relapses and deaths of children with acute lymphoblastic leukemia: role of allogeneic stem-cell transplantation in Nordic data. J Clin Oncol. 2006;24(36):5750–62.

    Article  PubMed  Google Scholar 

  2. Mullighan CG, Goorha S, Radtke I, Miller CB, Coustan-Smith E, Dalton JD, et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature. 2007;446(7137):758–64.

    Article  PubMed  CAS  Google Scholar 

  3. Iacobucci I, Lonetti A, Paoloni F, Papayannidis C, Ferrari A, Storlazzi CT, et al. The PAX5 gene is frequently rearranged in BCR-ABL1-positive acute lymphoblastic leukemia but is not associated with outcome. A report on behalf of the GIMEMA Acute Leukemia Working Party. Haematologica. 2010;95(10):1683–90.

    Article  PubMed  CAS  Google Scholar 

  4. Kim M, Choi JE, She CJ, Hwang SM, Shin HY, et al. PAX5 deletion is common and concurrently occurs with CDKN2A deletion in B-lineage acute lymphoblastic leukemia. Blood Cells Mol Dis. 2011;47(1):62–6.

    Article  PubMed  CAS  Google Scholar 

  5. Delogu A, Schebesta A, Sun Q, Aschenbrenner K, Perlot T, et al. Gene repression by Pax5 in B cells is essential for blood cell homeostasis and is reversed in plasma cells. Immunity. 2006;24(3):269–81.

    Article  PubMed  CAS  Google Scholar 

  6. Schebesta A, McManus S, Salvagiotto G, Delogu A, Busslinger GA, Busslinger M. Transcription factor Pax5 activates the chromatin of key genes involved in B cell signaling, adhesion, migration, and immune function. Immunity. 2007;27(1):49–63.

    Article  PubMed  CAS  Google Scholar 

  7. Nutt SL, Heavey B, Rolink AG, Busslinger M. Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. Nature. 1999;401(6753):556–62.

    Article  PubMed  CAS  Google Scholar 

  8. Heltemes-Harris LM, Willette MJ, Ramsey LB, Qiu YH, Neeley ES, Zhang N, Thomas DA, Koeuth T, Baechler EC, Kornblau SM, Farrar MA. Ebf1 or Pax5 haploinsufficiency synergizes with STAT5 activation to initiate acute lymphoblastic leukemia. J Exp Med. 2011;208(6):1135–49.

    Article  PubMed  CAS  Google Scholar 

  9. Li X, Cheung KF, Ma X, Tian L, Zhao J, Go MY, Shen B, Cheng AS, Ying J, Tao Q, Sung JJ, Kung HF, Yu J. Epigenetic inactivation of paired box gene 5, a novel tumor suppressor gene, through direct upregulation of p53 is associated with prognosis in gastric cancer patients. Oncogene. 2012;31(29):3419–30.

    Article  PubMed  CAS  Google Scholar 

  10. Mullighan CG, Su X, Zhang J, Radtke I, Phillips LA, Miller CB, et al. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med. 2009;360(5):470–80.

    Article  PubMed  CAS  Google Scholar 

  11. Tusher VG, Tibshirani R, Chu G. Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA. 2001;98:5116–21.

    Article  PubMed  CAS  Google Scholar 

  12. Simon R, Lam A, Li MC, Ngan M, Menenzes S, Zhao Y. Analysis of gene expression data using BRB-ArrayTools. Cancer Inform. 2007;3:11–7.

    PubMed  Google Scholar 

  13. Welch JS, Link DC. Genomics of AML: clinical applications of next-generation sequencing. Hematol Am Soc Hematol Educ Program. 2011;2011:30–5.

    Article  Google Scholar 

  14. Miller CB, Mullighan CG, Su X, Ma J, Wang M, Zhang J, Williams RT, Downing JR. Pax5 Haploinsufficiency cooperates with BCR-ABL1 to induce acute lymphoblastic leukemia ASH. Annu Meeting Abstr. 2008;112:293.

    Google Scholar 

  15. Saitoh F, Araki T. Proteasomal degradation of glutamine synthetase regulates Schwann cell differentiation. J Neurosci. 2010;30(4):1204–12.

    Article  PubMed  CAS  Google Scholar 

  16. Yoshida K, Watanabe M, Hatakeyama S. ZNRF1 interacts with tubulin and regulates cell morphogenesis. Biochem Biophys Res Commun. 2009;389(3):506–11.

    Article  PubMed  CAS  Google Scholar 

  17. Wakatsuki S, Saitoh F. Araki T.ZNRF1 promotes Wallerian degeneration by degrading AKT to induce GSK3B-dependent CRMP2 phosphorylation. Nat Cell Biol. 2011;13(12):1415–23.

    Article  PubMed  CAS  Google Scholar 

  18. Xu N, Lao Y, Zhang Y, Gillespie DA. Akt: a double-edged sword in cell proliferation and genome stability. J Oncol. 2012;2012:951724 (Epub 15 Mar 2012).

    Google Scholar 

  19. Anderhub SJ, Krämer A, Maier B. Centrosome amplification in tumorigenesis. Cancer Lett. 2012;322(1):8–17.

    Article  PubMed  CAS  Google Scholar 

  20. Thoma CR, Frew IJ, Krek W. The VHL tumor suppressor: riding tandem with GSK3beta in primary cilium maintenance. Cell Cycle. 2007;6(15):1809–13.

    Article  PubMed  CAS  Google Scholar 

  21. Thoma CR, Toso A, Gutbrodt KL, Reggi SP, Frew IJ, Schraml P, et al. VHL loss causes spindle misorientation and chromosome instability. Nat Cell Biol. 2009;11(8):994–1001.

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wei Huang.

Electronic supplementary material

Below is the link to the electronic supplementary material.

12185_2013_1309_MOESM1_ESM.tif

Supplementary material 1 PAX5 deletions in B-ALL patients. Deletions were analyzed on 2% agarose gel. M is a 100 bp DNA ladder, P1 have strong Δ7/8/9 expression besides full length (FL). P2 have Δ7/8 but have no FL expression.P3, P4 and P6 have FL and Δ7/8 and P5 have FL, Δ8, Δ7/8. (TIFF 169 kb)

Supplementary material 2 Identification of mutations in two B-ALL patients:T303A,T252I (TIFF 116 kb)

Supplementary material 3 Identification of deletions: Deletion of exon 7/8/9 and exon 8. (TIFF 351 kb)

Supplementary material 4 (DOCX 16 kb)

About this article

Cite this article

Shang, Z., Zhao, Y., Zhou, K. et al. PAX5 alteration-associated gene-expression signatures in B-cell acute lymphoblastic leukemia. Int J Hematol 97, 599–603 (2013). https://doi.org/10.1007/s12185-013-1309-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-013-1309-9

Keywords

Navigation