Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Chronic Myeloproliferative Disorders

Heterogeneity in detecting Abl kinase mutations and better sensitivity using circulating plasma RNA

Abstract

Most studies test for mutations in the kinase domain of the abl gene in chronic myeloid leukemia (CML) using peripheral blood (PB) cells. Frequently, progression of the disease manifests with increased blasts in bone marrow (BM) and not in PB. Simultaneous analysis of plasma, PB cells and BM cells from 41 imatinib-resistent CML patients showed mutations in 63% of PB cells and 68% of plasma or BM cells (P=0.04). In discordant patients, 13 mutations were detected in plasma, 11 in BM cells and 9 in PB cells. The T315I mutation was detected in plasma and BM but not PB cells in one patient. We detected no mutations in the plasma of 45 previously untreated CML patients, but two of these patients showed mutations in plasma and not cells by 9 months on therapy. Circulating plasma mRNA is a reliable alternative to BM mRNA for detecting ABL mutations.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti-Passerini C et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 2002; 346: 645–652.

    Article  CAS  Google Scholar 

  2. Muller MC, Gattermann N, Lahaye T, Deininger MW, Berndt A, Fruehauf S et al. Dynamics of BCR-ABL mRNA expression in first-line therapy of chronic myelogenous leukemia patients with imatinib or interferon alpha/ara-C. Leukemia 2003; 17: 2392–2400.

    Article  CAS  Google Scholar 

  3. O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2003; 348: 994–1004.

    Article  CAS  Google Scholar 

  4. Hochhaus A, La Rosee P . Imatinib therapy in chronic myelogenous leukemia: strategies to avoid and overcome resistance. Leukemia 2004; 18: 1321–1331.

    Article  CAS  Google Scholar 

  5. Deininger M, Buchdunger E, Druker BJ . The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood 2005; 105: 2640–2653.

    Article  CAS  Google Scholar 

  6. Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 2001; 293: 876–880.

    Article  CAS  Google Scholar 

  7. Branford S, Rudzki Z, Walsh S, Parkinson I, Grigg A, Szer J et al. Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis. Blood 2003; 102: 276–283.

    Article  CAS  Google Scholar 

  8. O'Hare T, Walters DK, Deininger MW, Druker BJ . AMN107: tightening the grip of imatinib. Cancer Cell 2005; 7: 117–119.

    Article  CAS  Google Scholar 

  9. Weisberg E, Manley PW, Breitenstein W, Bruggen J, Cowan-Jacob SW, Ray A et al. Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell 2005; 7: 129–141.

    Article  CAS  Google Scholar 

  10. Albitar M, Do KA, Johnson MM, Giles FJ, Jilani I, O'Brien S et al. Free circulating soluble CD52 as a tumor marker in chronic lymphocytic leukemia and its implication in therapy with anti-CD52 antibodies. Cancer 2004; 101: 999–1008.

    Article  CAS  Google Scholar 

  11. Manshouri T, Do KA, Wang X, Giles FJ, O'Brien S, Safer H et al. Circulating CD20 is detectable in the plasma of patients with chronic lymphocytic leukemia and is of prognostic significance. Blood 2003; 101: 2507–2513.

    Article  CAS  Google Scholar 

  12. Ahmed M, Giles F, Joe Y, Weber DM, Jilani I, Manshouri T et al. Use of plasma DNA in detection of loss of heterozygosity in patients with multiple myeloma. Eur J Haematol 2003; 71: 174–178.

    Article  CAS  Google Scholar 

  13. Rogers A, Joe Y, Manshouri T, Dey A, Jilani I, Giles F et al. Relative increase in leukemia-specific DNA in peripheral blood plasma from patients with acute myeloid leukemia and myelodysplasia. Blood 2004; 103: 2799–2801.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M Albitar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ma, W., Kantarjian, H., Jilani, I. et al. Heterogeneity in detecting Abl kinase mutations and better sensitivity using circulating plasma RNA. Leukemia 20, 1989–1991 (2006). https://doi.org/10.1038/sj.leu.2404355

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404355

Keywords

This article is cited by

Search

Quick links