Skip to main content

Advertisement

SpringerLink
Log in

Constitutional t(8;22)(q24;q11.2) that mimics the variant Burkitt-type translocation in Philadelphia chromosome-positive chronic myeloid leukemia

  • Case Report
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Constitutional translocations that coincide with t(9;22)(q34;q11.2) may lead to unnecessary treatments in chronic myeloid leukemia (CML) patients, as, under the standard criteria, a diagnosis of CML with additional chromosomal abnormalities indicates an accelerated phase (AP). In the present report, a 47-year-old male had pain in the right foot due to gout. Peripheral blood examination showed leukocytosis with left shift. Bone marrow aspiration revealed myeloid hyperplasia with megakaryocytosis. RT-PCR revealed the major BCR-ABL fusion transcript, and CML in the chronic phase was diagnosed, followed by nilotinib treatment. Although WBC counts decreased immediately, G-banding analysis showed 46,XY,t(8;22)(q24;q11.2),t(9;22)(q34;q11.2) [20]. The t(8;22)(q24;q11.2) translocation is known to be recurrent in Burkitt’s lymphoma. The diagnosis was changed to CML in AP, leading to B-lymphoid crisis. Unexpectedly, the karyotype was 46,XY,t(8;22)(q24;q11.2) [20] in hematological complete remission, even after 3 months. Fluorescence in situ hybridization on metaphase spreads revealed the MYC signal on the der(22)t(8;22), indicating that the 8q24 breakpoint was centromeric to MYC at 8q24.21. G-banding analysis of phytohemagglutinin-stimulated peripheral blood T-lymphocytes also indicated 46,XY,t(8;22)(q24.1;q11.2). We conclude that the t(8;22) is constitutional in this patient. As the tumor suppressor gene TRC8/RNF139 is disrupted by constitutional t(8;22)(q24.13;q11.21) in dysgerminoma, it may be associated with the onset of CML.

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. Mitelman F, Leavan G, Nilsson PG, Brandt L. Non-random karyotypic evolution in chronic myeloid leukemia. Int J Cancer. 1976;18(1):24–30.

    Article  CAS  PubMed  Google Scholar 

  2. Wang W, Cortes JE, Tang G, Khoury JD, Wang S, Bueso-Ramos CE, et al. Risk stratification of chromosomal abnormalities in chronic myelogenous leukemia in the era of tyrosine kinase inhibitor therapy. Blood. 2016;127(22):2742–50.

    Article  CAS  PubMed  Google Scholar 

  3. Wennström J, Schröder J. A t(13q14q) Family with the translocation and a Philadelphia chromosome in one member. Hum Genet. 1973;20(1):71–3.

    Article  Google Scholar 

  4. Kohno S, Sandberg AA. Ph1-positive CML in a 13;14 translocation carrier. Med Pediatr Oncol. 1978;5(1):61–4.

    Article  CAS  PubMed  Google Scholar 

  5. Qian J, Xue Y, Sun J, Guo Y, Pan J, Wu Y, et al. Constitutional Robertsonian translocations in (9;22)-positive chronic myelogenous leukemia. Cancer Genet Cytogenet. 2002;132(1):79–80.

    Article  CAS  PubMed  Google Scholar 

  6. Becker R, Mahmoud HK, Schaefer UW, Schmidt CG. Ph-positive CML in a family with a constitutional Robertsonian translocation 14;15. Cancer Genet Cytogenet. 1985;18(3):229–34.

    Article  Google Scholar 

  7. Becker R, Wendt F, Kuhn D. Constitutional Robertsonian t(15;22) in Ph-positive CML. Hum Genet. 1987;76(4):399.

    Article  Google Scholar 

  8. Kajtar B, Deák L, Kalász V, Pajor L, Molnár L, Méhes G. Multiple constitutional chromosome translocations of familial nature in Philadelphia chromosome-positive chronic myeloid leukemia: a report on a unique case. Int J Hematol. 2005;82(4):347–50.

    Article  PubMed  Google Scholar 

  9. Zeidler R, Joos S, Delecluse HJ, Klobeck G, Vuilaume M, Lenoir GM, et al. Breakpoints of Burkitt’s lymphoma t(8;22) translocations map within a distance of 300 kb downstream of MYC. Genes Chromosom Cancer. 1994;9(4):282–7.

    Article  CAS  PubMed  Google Scholar 

  10. Sheridan MB, Kato T, Haldeman-Englert C, Jalali GR, Milunsky JM, Zou Y, et al. A palindrome-mediated recurrent translocation with 3:1 meiotic nondisjunction: the t(8;22)(q24.13;q11.21). Am J Hum Genet. 2010;87(2):209–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ohye T, Inagaki H, Kogo H, Tsutsumi M, Kato T, Tong M, et al. Paternal origin of the de novo constitutional t(11;22)(q23;q11). Eur J Hum Genet. 2010;18(7):783–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Petit P, Vermeersch JR, Fryns JP. Identification of a de novo 46, XY,4p + with incomplete Wolf-Hirschhorn syndrome as 46, XY, der(4)t(4;8)(p16.3;p23.1). Genet Couns. 1998;9(2):157–8.

    CAS  PubMed  Google Scholar 

  13. Tönnies H, Stumm M, Neumann L, Volleth M, Grumpelt U, Müsebeck J, et al. Two further cases of WHS with unbalanced de novo translocation t(4;8) characterised by CGH and FISH. J Med Genet. 2001;38(6):E21.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Czuchlewski DR, Farzanmehr H, Robinett S, Haines S, Reichard KK. t(9;22)(q34;q11.2) is a recurrent constitutional non-Robertsonian translocation and a rare cytogenetic mimic of chronic myeloid leukemia. Cancer Genet. 2011;204(10):572–6.

    CAS  PubMed  Google Scholar 

  15. Keung YK, Knovich MA, Molnar I, Pettenati M. Constitutional t(8;22) in a patient with myasthenia gravis, leukocytosis, and thrombocytosis. Cancer Gent Cytogenet. 2004;148(1):87–8.

    Article  Google Scholar 

  16. Edelmann L, Pandita RK, Spiteri E, Funke B, Goldberg R, Palanisamy N, et al. A common molecular basis for rearrangement disorders on chromosome 22q11. Hum Mol Genet. 1999;8(7):1157–67.

    Article  CAS  PubMed  Google Scholar 

  17. Shaikh TH, Kurahashi H, Saitta SC, O’Hare AM, Hu P, Roe BA, et al. Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis. Hum Mol Genet. 2000;9(4):489–501.

    Article  CAS  PubMed  Google Scholar 

  18. Gotter AL, Nimmakayalu MA, Jalali GR, Hacker AM, Vorstman J, Conforto Duffy D, et al. A palindrome-driven complex rearrangement of 22q11.2 and 8q24.1 elucidated using novel technologies. Genome Res. 2007;17(4):470–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mishra D, Kato T, Inagaki H, Kosho T, Wakui K, Kido Y, et al. Breakpoint analysis of the recurrent constitutional t(8;22)(q24.13;q11.21) translocation. Mol Cytogenet. 2014;7:55.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Gimelli S, Beri S, Drabkin HA, Gambini C, Gregorio A, Fiorio P, et al. The tumor suppressor gene TRC8/RNF139 is disrupted by a constitutional balanced translocation t(8;22)(q24.13;q11.21) in a young girl with dysgerminoma. Mol Cancer. 2009;8:52.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Gemmill RM, Bemis LT, Lee JP, Sozen MA, Baron A, Zeng C, et al. The TRC8 hereditary kidney cancer gene suppresses growth and functions with VHL in a common pathway. Oncogene. 2002;21(22):3507–16.

    Article  CAS  PubMed  Google Scholar 

  22. Tomoda K, Kubota Y, Kato J. Degradation of the cyclin-dependent-kinase inhibitor p27Kip1 is instigated by Jab1. Nature. 1999;398(6723):160–5.

    Article  CAS  PubMed  Google Scholar 

  23. Payne SR, Zhang S, Tsuchiya K, Moser R, Gurley KE, Longton G, et al. p27kip1 deficiency impairs G2/M arrest in response to DNA damage, leading to an increase in genetic instability. Mol Cell Biol. 2008;28(1):258–68.

    Article  CAS  PubMed  Google Scholar 

  24. Gemmil RM, West JD, Boldog F, Tanaka N, Robinson LJ, Smith DI, et al. The hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a patched-related gene, TRC8. Proc Natl Acad Sci USA. 1998;95(16):9572–7.

    Article  Google Scholar 

  25. Poland KS, Azim M, Folsom M, Goldfarb R, Naeem R, Korch C, et al. A constitutional balanced t(3;8)(p14;q24.1) translocation results in disruption of the TRC8 gene and predisposition to clear cell renal cell carcinoma. Genes Chromosom Cancer. 2007;46(9):805–12.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Oncology/Hematology, Kobe University Hospital, Chuoh-ku Kusunokicho 7-5-2, Kobe City, Hyogo, 650-0017, Japan

    Shinichiro Kawamoto, Katsuya Yamamoto, Masanori Toyoda, Kimikazu Yakushijin, Hiroshi Matsuoka & Hironobu Minami

Authors
  1. Shinichiro Kawamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katsuya Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masanori Toyoda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kimikazu Yakushijin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroshi Matsuoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hironobu Minami
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shinichiro Kawamoto.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kawamoto, S., Yamamoto, K., Toyoda, M. et al. Constitutional t(8;22)(q24;q11.2) that mimics the variant Burkitt-type translocation in Philadelphia chromosome-positive chronic myeloid leukemia. Int J Hematol 105, 226–229 (2017). https://doi.org/10.1007/s12185-016-2100-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-016-2100-5

Keywords

Search

Navigation