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.

  • Correspondence
  • Published:

The paternal chromosome 9 and the maternal chromosome 22 are preferentially rearranged in chronic myeloid leukaemia

Leukemia volume 18, pages 1445–1448 (2004)Cite this article

An Erratum to this article was published on 23 August 2004

TO THE EDITOR

In the majority of patients with chronic myeloid leukaemia (CML), a reciprocal chromosome translocation t(9;22)(q34.1;q11.2) originates two derived products known as the Philadelphia (Ph) chromosome and 9q+ following rearrangement at definite BCR and ABL regions.1 While breakpoints are well characterised at the cytogenetic and molecular levels, the parental origin of the rearranged chromosomes is controversial.2, 3, 4, 5, 6, 7 To clarify this issue, we analysed cell hybrids segregating the derived chromosomes and the normal, nonrearranged, chromosomes 9 and 22. Cell hybrid panels were created with bone marrow aspirates from four CML patients following cell fusion with recipient, Hprt-deficient, rodent cell lines (RAG and AKO-15). The four panels derived from the patients were PCR screened for amplifying variable markers located in regions across 9q34.1 and 22q11.2 breakpoints (Tables 1 and 2). This allowed us to separate hybrid cell lines into different classes per panel: 9+ (cells containing chromosome 9 and lacking 9q+, 22 and Ph), 9q+ (containing the 9q+ chromosome and lacking 9, 22 and Ph), 22+ (containing chromosome 22 and lacking 9, 9q+ and Ph) and Ph+ (containing the Ph chromosome and lacking 9, 9q+ and 22). All Ph+ lines, when screened by multiplex RT-PCR,8 detected BCR-ABL transcripts, subsequently confirmed by cDNA sequencing, demonstrating the presence of a transcriptionally active BCR-ABL gene. Another cell hybrid class, 9+/22+, containing both 9q and 22q regions across breakpoints and shown to be BCR-ABL+ by PCR assays, was also identified and two of these cell lines were used as control in each panel. These cell lines must contain, at least, the normal chromosomes 9 and 22 in addition to the Ph chromosome or the 9q+ chromosome and the Ph chromosome. Altogether, 53 hybrid cell lines, derived from four patients, were analysed (Table 3).

Table 1 Amplimers used for the amplification of chromosome 9 markers
Full size table
Table 2 Amplimers used for the amplification of chromosome 22 markers
Full size table
Table 3 Hybrid cell classes and the number of hybrid cell lines per panel
Full size table

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

References

  1. Barnes DJ, Melo JV . Cytogenetic and molecular genetic aspects of chronic myeloid leukemia. Acta Haematol 2002; 108: 180–202.

    Article  CAS  PubMed  Google Scholar 

  2. Haas OA, Argyriou-Tirita A, Lion T . Parental origin of chromosomes involved in the translocation 9;22. Nature 1992; 359: 414–416.

    Article  CAS  PubMed  Google Scholar 

  3. Riggins GJ, Sherman SL, Phillips CN, Stock W, Westbrook CA, Warren ST . CGG-repeat polymorphism of the BCR gene rules out predisposing alleles leading to the Philadelphia chromosome. Genes Chromosomes Cancer 1994; 9: 141–144.

    Article  CAS  PubMed  Google Scholar 

  4. Litz CE, Copenhaver CM . Paternal origin of the major breakpoint cluster region in chronic myeloid leukemia. Blood 1994; 83: 3445–3448.

    CAS  PubMed  Google Scholar 

  5. Maserati E, Seghezzi L, Pasquali F, Locatelli F . Parental origin of chromosomes 9 and 22 involved in the Ph chromosome translocation in chronic myelocytic leukemia. Cancer Genet Cytogenet 1998; 107: 151–152.

    Article  CAS  PubMed  Google Scholar 

  6. Nakamura H, Itoyama T, Niikawa N, Sadamori N, Tomonaga M . No parental origin bias for the rearranged chromosomes in myeloid leukemias associated with t(9;22), t(8;21) and t(15;17). Leukemia Res 1998; 22: 793–796.

    Article  CAS  Google Scholar 

  7. Melo JV, Xiu-Hua Y, Diamond J, Goldman JM . Balanced parental contribution to the ABL component of the BCR-ABL gene in chronic myeloid leukemia. Leukemia 1995; 9: 734–739.

    CAS  PubMed  Google Scholar 

  8. Cross NC, Melo JV, Feng L, Goldman JM . An optimized multiplex polymerase chain reaction (PCR) for detection of BCR-ABL fusion mRNAs in haematological disorders. Leukemia 1994; 8: 186–189.

    CAS  PubMed  Google Scholar 

  9. Janković GM, Čolović MD, Bogdanović AD, Čolović NR, Janković SJ . Parental reciprocation in t(9;22) vs genomic imprinting. Leukemia 1996; 10: 1402.

    PubMed  Google Scholar 

  10. Fioretos T, Heisterkamp N, Groffen J . No evidence for genomic imprinting of the human BCR gene. Blood 1994; 83: 3441–4344.

    CAS  PubMed  Google Scholar 

  11. Melo JV, Xiu-Hua Y, Diamond J, Goldman JM . Lack of imprinting of the ABL gene. Nat Genet 1994; 8: 318–319.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by Instituto Nacional de Câncer (INCA) and Fundação Ary Frauzino (Rio de Janeiro, Brazil). We are grateful to Drs Arthur Moellman and Claudete Klumb, to other members of the staff of the Haematology Service-INCA and the Bone Marrow Transplantation Centre-INCA for samples and clinical data. We are grateful to Claudio Vieira da Silva for technical support and to Amersham Biosciences for lending the MegaBACE Genetic profiler software. This work was approved by the local Committee of Medical Ethics in accordance with the guidelines of the Helsinki declaration.

Author information

Authors and Affiliations

  1. Genetics Division, Instituto Nacional de Câncer, Rio de Janeiro, Brazil

    R Olicio, M B Rivero & H N Seuánez

  2. Department of Genetics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    H N Seuánez

Authors
  1. R Olicio
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M B Rivero
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H N Seuánez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H N Seuánez.

Additional information

Supplementary information is available on the Leukemia website (http://www.nature.com/leu/).

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Olicio, R., Rivero, M. & Seuánez, H. The paternal chromosome 9 and the maternal chromosome 22 are preferentially rearranged in chronic myeloid leukaemia. Leukemia 18, 1445–1448 (2004). https://doi.org/10.1038/sj.leu.2403404

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2403404

Search

Advanced search

Quick links