Skip to main content
SpringerLink
Log in

Lineage-specific clonality analysis of chronic myeloproliferative disorders and myelodysplastic syndrome by human androgen receptor assay

  • Article
  • Published:
Pathology & Oncology Research

Abstract

In myelodysplastic syndrome (MDS) as well as chronic myeloproliferative disorders (CMPD) others than chronic myeloid leukemia the frequency of pathognomonic genetic aberrations is very low and, therefore, X chromosome inactivation (XI) assays may help in assessing the clonality. To establish specific clonality criteria on XI, human androgen receptor assay (HUMARA) was performed on sorted myeloid and lymphoid peripheral blood cells of 21 healthy females. Clonality criteria 1 and 2 conferring at least 90% specificity were set based on the ranges and differences of XI number (XIN) describing the ratio of representation of the two alleles in as well as in between reactive myeloid and lymphoid compartments. Spiking experiments indicated that the test identifies clonality reliably when no more than 40–50% reactive cells are admixed. In the CMPD and MDS cases peripheral myeloid cells were monoclonal by one of the two criteria in 71–100%, whereas lymphoid cells in 28–75%. The results of HUMARA, available in 73% of the female patients, supported the clinicopathological data in 84% as well as proved pluripotent stem cell origin in 31–75% and 21% of CMPDs and MDS, respectively.

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

Similar content being viewed by others

Abbreviations

CLL:

chronic lymphocytic leukemia

CML:

chronic myeloid leukemia

CMPD:

chronic myeloproliferative disorder

ET:

essential thrombocytemia

HES:

hypereosinophilic syndrome

MDS:

myelodysplastic syndrome

NRXI:

non-random Xinactivation

PMR:

polymorphic microsatellite region

PV:

polycythemia vera

XI:

X-inactivation

XIN:

X-inactivation number

References

  1. Allen RC, Zoghbi HY, Moseley AB: Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation. Am J Hum Genet 51:1229–1239, 1992

    PubMed  CAS  Google Scholar 

  2. Anderson JE, Gilliland DG, List AF: Myelodysplastic syndrome. Educational Materials by the American Society of Hematology, 1998

  3. Baxter EJ, Scott LM, Campbell PJ: Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365:1054–1061, 2005

    PubMed  Google Scholar 

  4. Busque L, Gilliland DG: X-inactivation analysis in the 1990s: promise and potential problems. Leukemia 12:128–135, 1998

    Article  Google Scholar 

  5. Culligan DJ, Cachia P, Wittaker J: Clonal lymphocytes are detectable in only some cases of MDS. Br J Haematol 81:346–352, 1992

    Article  PubMed  CAS  Google Scholar 

  6. Heaney ML, Golde DW: Myelodysplasia. N Engl J Med 340:1649–1660, 1999

    Article  PubMed  CAS  Google Scholar 

  7. Hellström-Lindberg E, Willmann C, Barrett AJ: Achievements in understanding and treatment of myelodysplastic syndromes. Educational Materials by the American Society of Hematology, 2000.

  8. Jaffe ES, Harris NL, Stein H, Vardinian JW eds. World Health Organization Classification of Tumours, Pathology & Genetics, Tumours of Haematopoietic and Lymphoid Tissues. IARC Press, Lyon, 2001

    Google Scholar 

  9. James C, Ugo V Le Couedic JP: A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 434:1144–1148, 2005

    Article  PubMed  Google Scholar 

  10. Knuutila S, Teerenhovi L, Larramendy ML: Cell lineage involvement of recurrent chromosomal abnormalities in hematological neoplasms. Genes, Chromosomes Cancer 10:95–102, 1994

    Article  PubMed  CAS  Google Scholar 

  11. Kralovics R, Passamonti F, Buser AS: A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 352:1779–1790, 2005

    Article  PubMed  Google Scholar 

  12. Levine RL, Wadleigh M, Cools J: Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocytemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 7:387–397, 2005

    Article  PubMed  Google Scholar 

  13. Nilsson L, Åstrand-Grundström I: Isolation and characterization of hematopoietic progenitor/stem cells in 5q-deleted myelodysplastic syndromes: evidence for involvement at the hematopoietic stem cell level. Blood 156:2012–2021, 2000

    Google Scholar 

  14. Pajor L, Matolcsy A, Vass JA, Méhes G, Marton É, Szabó F: Phenotypic and genotypic analyses of blastic cell population suggest that pure B-lymphoblastic leukemia may arise from myelodysplastic syndrome. Leuk Res 22:13–17, 1998

    Article  PubMed  CAS  Google Scholar 

  15. Pearson TC, Messinezy M, Westwood N: A Polycythemia Vera Update: diagnosis, pathobiology, and treatment. Educational Materials by the American Society of Hematology, 2000.

  16. Raskind WH, Steinmann L, Najfeld V: Clonal development of myeloproliferative disorders: clues to hematopoietic differentiation and multistep pathogenesis of cancer. Leukemia 12: 108–116, 1998

    Article  PubMed  CAS  Google Scholar 

  17. Tonon L, Bergamaschi G, Dellavecchia C, Rosti V, Lucotti C, Malabarba: Unbalanced X-chromosome inactivation in haematopoietic cells from normal women. Br J Haematol 102:996–1003, 1998

    Article  PubMed  CAS  Google Scholar 

  18. Zhao R, Xing S, Li Z: Identification of an acquired JAK2 mutation in Polycythemia vera. J Biol Chem 280:22788–22792, 2005

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Faculty of Medicine, University of Pécs, Pécs, Hungary

    Pál Jáksó, László Kereskai & László Pajor

  2. 1st Department of Internal Medicine, Faculty of Medicine, University of Pécs, Pécs, Hungary

    Lenke Molnár

Authors
  1. Pál Jáksó
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. László Kereskai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lenke Molnár
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. László Pajor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to László Pajor.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jáksó, P., Kereskai, L., Molnár, L. et al. Lineage-specific clonality analysis of chronic myeloproliferative disorders and myelodysplastic syndrome by human androgen receptor assay. Pathol. Oncol. Res. 13, 114–122 (2007). https://doi.org/10.1007/BF02893486

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02893486

Key words

Search

Navigation