Skip to main content
SpringerLink
Log in

Elevated β-arrestin1 expression correlated with risk stratification in acute lymphoblastic leukemia

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Acute lymphoblastic leukemia (ALL) is the main subtype of childhood leukemia. Risk stratification is pivotal for ALL prognosis and individualized therapy. The current factors for risk stratification include clinical and laboratory features, cytogenetic characteristics of the blast, early response to chemotherapy, and genetic factors. Analyses of gene expression are becoming increasingly important in ALL risk stratification. β-Arrestin1, a multifunctional scaffold protein mediating many intracellular signaling networks, has been shown to be involved in many tumors. However, little is known of β-arrestin1 in leukemia. In this study, we found that β-arrestin1 was significantly elevated in 155 newly diagnosed ALL patients, compared with 51 controls. Further analysis showed that β-arrestin1 expression was positively related with risk classification and white blood cell count in ALL. Moreover, expression of Notch1, an essential gene for developing hematological cells and T-ALL, was found to be negatively correlated with β-arrestin1 in ALL. In conclusion, β-arrestin1 may be a useful predictor of risk stratification and prognosis of ALL, and thus of potential use in the design of individualized therapy strategies.

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.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Rana ZA, Rabbani MW, Sheikh MA, Khan AA. Outcome of childhood acute lymphoblastic leukaemia after induction therapy-3 years experience at a single paediatric oncology centre. J Ayub Med Coll Abbottabad. 2009;21:150–3.

    PubMed  Google Scholar 

  2. Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. Lancet. 2008;371:1030–43.

    Article  CAS  PubMed  Google Scholar 

  3. Heuser M, Ganser A, Hoelzer D. The hematopoietic growth factors in acute leukemia: a European perspective. Cancer Treat Res. 2011;157:339–62.

    Article  CAS  PubMed  Google Scholar 

  4. Bauters T, Mondelaers V, Robays H, De Wilde H, Benoit Y, De Moerloose B. Methemoglobinemia and hemolytic anemia after rasburicase administration in a child with leukemia. Pharm World Sci. 2010 [Epub ahead of print].

  5. Karas Kuzelicki N, Milek M, Jazbec J, Mlinaric-Rascana I. 5,10-Methylenetetrahydrofolate reductase low activity genotypes reduce the risk of relapse-related acute lymphoblastic leukemia. Leuk Res. 2009;33:1344–8.

    Article  CAS  PubMed  Google Scholar 

  6. Rubnitz JE, Pui CH. Childhood acute lymphoblastic leukemia. Oncologist. 1997;2:374–80.

    CAS  PubMed  Google Scholar 

  7. Butturini A, Arlinghaus RB Gale RP. BCR/ABL and leukemia. Leuk Res. 1996;20(5):23–9.

    Google Scholar 

  8. Mansur MB, Enmerenciano M, Splendore A, Brewer L, Hassan Rand Pombo-de-Oliveira MS. T-cell lymphoblastic leukemia in early childhood presents NOTCH1 mutations and MLL rearrangements. Leuk Res. 2010;34:483–6.

    Article  CAS  PubMed  Google Scholar 

  9. Lefkowitz RJ, Whalen EJ. Beta-arrestins: traffic cops of cell signaling. Curr Opin Cell Biol. 2004;16:162–8.

    Article  CAS  PubMed  Google Scholar 

  10. Lefkowitz RJ, Shenoy SK. Transduction of receptor signals by beta-arrestins. Science. 2005;308:512–7.

    Article  CAS  PubMed  Google Scholar 

  11. DeWire SM, Ahn S, Lefkowitz RJ, Shenoy SK. Beta-arrestins and cell signaling. Annu Rev Physiol. 2007;69:483–510.

    Article  CAS  PubMed  Google Scholar 

  12. Luttrell LM, Lefkowitz RJ. The role of beta-arrestins in the termination and transduction of G-protein-coupled receptor signals. J Cell Sci. 2002;115:455–65.

    CAS  PubMed  Google Scholar 

  13. Kovacs JJ, Hara MR, Davenport CL, Kim J, Lefkowitz RJ. Arrestin development: emerging roles for beta-arrestins in developmental signaling pathways. Dev Cell. 2009;17:443–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Chen W, Kirkbride KC, How T, Nelson CD, Mo J, Frederick JP, et al. Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor and down-regulation of its signaling. Science. 2003;301:1394–7.

    Article  CAS  PubMed  Google Scholar 

  15. Girnita L, Shenoy SK, Sehat B, Vasilcanu R, Vaslcanu D, Girnita A, et al. Beta-arrestin and Mdm2 mediate IGF-1 receptor-stimulated ERK activation and cell cycle progression. J Biol Chem. 2007;282:11329–38.

    Article  CAS  PubMed  Google Scholar 

  16. Wang P, Gao H, Ni Y, Wang B, Wu Y, Ji L, et al. Beta-arrestin 2 functions as a G-protein-coupled receptor-activated regulator of oncoprotein Mdm2. J Biol Chem. 2003;278:6363–70.

    Article  CAS  PubMed  Google Scholar 

  17. Zou L, Yang R, Chai J, Pei G. Rapid xenograft tumor progression in beta-arrestin1 transgenic mice due to enhanced tumor angiogenesis. FASEB J. 2008;22:355–64.

    Article  CAS  PubMed  Google Scholar 

  18. Buchanan FG, Gorden DL, Matta P, Shi Q, Matrisian LM, DuBois RN. Role of beta-arrestin 1 in the metastatic progression of colorectal cancer. Proc Natl Acad Sci USA. 2006;103:1492–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yue R, Kang J, Zhao C, Hu W, Tang Y, Liu X, et al. Beta-arrestin1 regulates zebrafish hematopoiesis through binding to YY1 and relieving polycomb group repression. Cell. 2009;139:535–46.

    Article  CAS  PubMed  Google Scholar 

  20. Kalderon D. Similarities between the Hedgehog and Wnt signaling pathways. Trends Cell Biol. 2002;12:523–31.

    Article  CAS  PubMed  Google Scholar 

  21. Wilson JJ, Kovall RA. Crystal structure of the CSL-Notch-Mastermind ternary complex bound to DNA. Cell. 2006;124:985–96.

    Article  CAS  PubMed  Google Scholar 

  22. Nam Y, Sliz P, Song L, Aster JC, Blacklow SC. Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes. Cell. 2006;124:973–83.

    Article  CAS  PubMed  Google Scholar 

  23. Grabher C, von Boehmer H, Look AT. Notch 1 activation in the molecular pathogenesis of T-cell acute lymphoblastic leukaemia. Nat Rev Cancer. 2006;6:347–59.

    Article  CAS  PubMed  Google Scholar 

  24. Radtke F, Schweisguth F, Pear W. The Notch ‘gospel’. EMBO Rep. 2005;6:1120–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Weng AP, Ferrando AA, Lee W, 4th Morris JP, Silverman LB, Sanchez-lrizarrv C, et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science. 2004;306:269–71.

    Article  CAS  PubMed  Google Scholar 

  26. Girard L, Hanna Z, Beaulieu N, Hoemann CD, Simard C, Kozak CA, et al. Frequent provirus insertional mutagenesis of Notch1 in thymomas of MMTVD/myc transgenic mice suggests a collaboration of c-myc and Notch1 for oncogenesis. Genes Dev. 1996;10:1930–44.

    Article  CAS  PubMed  Google Scholar 

  27. Feldman BJ, Hampton T, Cleary ML. A carboxy-terminal deletion mutant of Notch1 accelerates lymphoid oncogenesis in E2A-PBX1 transgenic mice. Blood. 2000;96:1906–13.

    CAS  PubMed  Google Scholar 

  28. Beverly LJ, Capobianco AJ. Perturbation of Ikaros isoform selection by MLV integration is a cooperative event in Notch(IC)-induced T cell leukemogenesis. Cancer Cell. 2003;3:551–64.

    Article  CAS  PubMed  Google Scholar 

  29. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, et al. Proposed revised criteria for the classification of acute myeloid leukaemia. A report of the French–American–British Cooperative Group. Ann Intern Med. 1985;103:620–5.

    Article  CAS  PubMed  Google Scholar 

  30. Wolowiec D, Mekki Y, French P, Manel AM, Bertrand Y, Rimokh R, et al. Differential expression of cell proliferation regulatory proteins in B- and T-lineage acute lymphoblastic leukaemias. Br J Haematol. 1996;l95:518–23.

    Article  Google Scholar 

  31. Smith M, Arthur D, Camitta B, Carroll AJ, Crist W, Gaynon P, et al. Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia. J Clin Oncol. 1996;14:18–24.

    Article  CAS  PubMed  Google Scholar 

  32. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402–8.

    Article  CAS  PubMed  Google Scholar 

  33. Beaulieu JM, Caron MG. Beta-arrestin goes nuclear. Cell. 2005;123:755–7.

    Article  CAS  PubMed  Google Scholar 

  34. Matsubayashi J, Takanashi M, Oikawa K, Fujita K, Tanaka M, Xu M, et al. Expression of G protein-coupled receptor kinase 4 is associated with breast cancer tumourigenesis. J Pathol. 2008;216:317–27.

    Article  CAS  PubMed  Google Scholar 

  35. Nobles KN, Guan Z, Xiao K, Oas TG, Lefkowitz RJ. The active conformation of beta-arrestin1: direct evidence for the phosphate sensor in the N-domain and conformational differences in the active states of beta-arrestins1 and -2. J Biol Chem. 2007;282:21370–81.

    Article  CAS  PubMed  Google Scholar 

  36. Kang J, Shi Y, Xaing B, Qu B, Su W, Zhu M, et al. A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription. Cell. 2005;123:833–47.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (90919013, 30871103), Natural Science Foundation of Chongqing (2008BB5072, 2010BA5008), and New Century Talented Program from Ministry of Chinese Education (NCET-2008). The authors would like to express their sincere thanks to the contribution of all patients and their families in this study.

Conflict of interest

The authors have no conflicts of interest to declare.

Author information

Authors and Affiliations

  1. Center for Clinical Molecular Medicine, Children’s Hospital, Key Laboratory of Developmental Disease in the Ministry of Education, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing Medical University, Chongqing, 400014, China

    Hui Liu, Juan Long, Peng-hui Zhang, Kang Li, Jun-jie Tan & Lin Zou

  2. Department of Blood Transfusion, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China

    Hui Liu

  3. Department of Clinical Biochemistry, Key Laboratory of Laboratory Medical Diagnostics in the Ministry of Education, Chongqing Medical University, Chongqing, China

    Juan Long & Zhi-guang Tu

  4. Department of Laboratory Medicine, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China

    Bin Sun

  5. Department of Hematology, Children’s Hospital, Chongqing Medical University, Chongqing, China

    Jie Yu

Authors
  1. Hui Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Juan Long
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peng-hui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jun-jie Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bin Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jie Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zhi-guang Tu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lin Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lin Zou.

About this article

Cite this article

Liu, H., Long, J., Zhang, Ph. et al. Elevated β-arrestin1 expression correlated with risk stratification in acute lymphoblastic leukemia. Int J Hematol 93, 494–501 (2011). https://doi.org/10.1007/s12185-011-0824-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-011-0824-9

Keywords

Search

Navigation