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Myelodysplasias

Trisomy 11 in myelodysplastic syndromes defines a unique group of disease with aggressive clinicopathologic features

Leukemia volume 24, pages 740–747 (2010)Cite this article

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Abstract

Trisomy 11 in myelodysplastic syndromes (MDS) is rare, with undefined clinical significance and is currently assigned to the International Prognostic Scoring System (IPSS) intermediate-risk group. Over a 15-year period, we identified 17 MDS patients with trisomy 11 either as a sole abnormality (n=10) or associated with one or two additional alterations (n=7), comprising 0.3% of all MDS cases reviewed. Of 16 patients with Bone Marrow material available for review, 14 (88%) patients presented with excess blasts, 69% patients evolved to acute myeloid leukemia (AML) in a 5-month median interval and the median survival was 14 months. For comparison, we studied 19 AML patients with trisomy 11 in a noncomplex karyotype, of which, a substantial subset of patients had morphologic dysplasia, and/or preexisting cytopenia(s)/MDS. Genomic DNA PCR showed MLL partial tandem duplication in 5 of 10 MDS and 7 of 11 AML patients. A review of literature identified 17 additional cases of MDS with trisomy 11, showing similar clinicopathologic features to our patients. Compared with our historical data comprising 1165 MDS patients, MDS patients with trisomy 11 had a significantly inferior survival to patients in the IPSS intermediate-risk cytogenetic group (P=0.0002), but comparable to the poor-risk group (P=0.97). We conclude that trisomy 11 in MDS correlates with clinical aggressiveness, may suggest an early/evolving AML with myelodysplasia-related changes and is best considered a high-risk cytogenetic abnormality in MDS prognostication.

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References

  1. Slovak ML, Traweek ST, Willman CL, Head DR, Kopecky KJ, Magenis RE et al. Trisomy 11: an association with stem/progenitor cell immunophenotype. Br J Haematol 1995; 90: 266–273.

    Article  CAS  Google Scholar 

  2. Sierra M, Hernandez JM, Garcia JL, Gutierrez NC, Perez JJ, Vidriales MB et al. Hematological, immunophenotypic, and cytogenetic characteristics of acute myeloblastic leukemia with trisomy 11. Cancer Genet Cytogenet 2005; 160: 68–72.

    Article  CAS  Google Scholar 

  3. Caligiuri MA, Strout MP, Schichman SA, Mrozek K, Arthur DC, Herzig GP et al. Partial tandem duplication of ALL1 as a recurrent molecular defect in acute myeloid leukemia with trisomy 11. Cancer Res 1996; 56: 1418–1425.

    CAS  PubMed  Google Scholar 

  4. Bernard OA, Romana SP, Schichman SA, Mauchauffe M, Jonveaux P, Berger R . Partial duplication of HRX in acute leukemia with trisomy 11. Leukemia 1995; 9: 1487–1490.

    CAS  PubMed  Google Scholar 

  5. Schichman SA, Caligiuri MA, Gu Y, Strout MP, Canaani E, Bloomfield CD et al. ALL-1 partial duplication in acute leukemia. Proc Natl Acad Sci USA 1994; 91: 6236–6239.

    Article  CAS  Google Scholar 

  6. Rege-Cambrin G, Giugliano E, Michaux L, Stul M, Scaravaglio P, Serra A et al. Trisomy 11 in myeloid malignancies is associated with internal tandem duplication of both MLL and FLT3 genes. Haematologica 2005; 90: 262–264.

    CAS  PubMed  Google Scholar 

  7. Collado R, Badia L, Garcia S, Sanchez H, Prieto F, Carbonell F . Chromosome 11 abnormalities in myelodysplastic syndromes. Cancer Genet Cytogenet 1999; 114: 58–61.

    Article  CAS  Google Scholar 

  8. Gangji D, Noseda A, Wybran J, Verhest A . Trisomy 11 in preleukemia. Cancer Genet Cytogenet 1985; 14: 119–123.

    Article  CAS  Google Scholar 

  9. Morgan R, Greene MH, Sandberg AA . Trisomy 11 in myelodysplasia. Cancer Genet Cytogenet 1988; 30: 159–162.

    Article  CAS  Google Scholar 

  10. Takasaki N, Kaneko Y, Maseki N, Sakurai M . Trisomy 11 in chronic myelomonocytic leukemia: report of two cases and review of the literature. Cancer Genet Cytogenet 1988; 30: 109–117.

    Article  CAS  Google Scholar 

  11. Weh HJ, Hoffmann R, Suciu S, Kuse R, Hossfeld DK . Is trisomy 11 another nonrandom chromosomal anomaly in acute nonlymphocytic leukemia and myelodysplastic syndromes? Cancer Genet Cytogenet 1988; 35: 205–211.

    Article  CAS  Google Scholar 

  12. Yamamoto K, Hamaguchi H, Nagata K, Kobayashi M, Taniwaki M . Tandem duplication of the MLL gene in myelodysplastic syndrome-derived overt leukemia with trisomy 11. Am J Hematol 1997; 55: 41–45.

    Article  CAS  Google Scholar 

  13. Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997; 89: 2079–2088.

    CAS  PubMed  Google Scholar 

  14. Pozdnyakova O, Miron PM, Tang G, Walter O, Raza A, Woda B et al. Cytogenetic abnormalities in a series of 1,029 patients with primary myelodysplastic syndromes: a report from the US with a focus on some undefined single chromosomal abnormalities. Cancer 2008; 113: 3331–3340.

    Article  Google Scholar 

  15. Brunning B, Orazi A, Germing U, Le Beau M, Porwit A, Baumann I et al. Myelodysplastic Syndromes/Neoplasms, vol. 2008. IARC Press: Lyon, 2008.

    Google Scholar 

  16. Gustincich S, Manfioletti G, Del Sal G, Schneider C, Carninci P . A fast method for high-quality genomic DNA extraction from whole human blood. Biotechniques 1991; 11: 298–300, 302.

    CAS  PubMed  Google Scholar 

  17. Caligiuri MA, Schichman SA, Strout MP, Mrozek K, Baer MR, Frankel SR et al. Molecular rearrangement of the ALL-1 gene in acute myeloid leukemia without cytogenetic evidence of 11q23 chromosomal translocations. Cancer Res 1994; 54: 370–373.

    CAS  PubMed  Google Scholar 

  18. Lin P, Jones D, Medeiros LJ, Chen W, Vega-Vazquez F, Luthra R . Activating FLT3 mutations are detectable in chronic and blast phase of chronic myeloproliferative disorders other than chronic myeloid leukemia. Am J Clin Pathol 2006; 126: 530–533.

    Article  CAS  Google Scholar 

  19. Zuo Z, Chen SS, Chandra PK, Galbincea JM, Soape M, Doan S et al. Application of COLD-PCR for improved detection of KRAS mutations in clinical samples. Mod Pathol 2009; 22: 1023–1031.

    Article  CAS  Google Scholar 

  20. Haase D, Germing U, Schanz J, Pfeilstocker M, Nosslinger T, Hildebrandt B et al. New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood 2007; 110: 4385–4395.

    Article  CAS  Google Scholar 

  21. Bernasconi P, Klersy C, Boni M, Cavigliano PM, Calatroni S, Giardini I et al. World Health Organization classification in combination with cytogenetic markers improves the prognostic stratification of patients with de novo primary myelodysplastic syndromes. Br J Haematol 2007; 137: 193–205.

    Article  CAS  Google Scholar 

  22. Steudel C, Wermke M, Schaich M, Schakel U, Illmer T, Ehninger G et al. Comparative analysis of MLL partial tandem duplication and FLT3 internal tandem duplication mutations in 956 adult patients with acute myeloid leukemia. Genes Chromosomes Cancer 2003; 37: 237–251.

    Article  CAS  Google Scholar 

  23. Shiah HS, Kuo YY, Tang JL, Huang SY, Yao M, Tsay W et al. Clinical and biological implications of partial tandem duplication of the MLL gene in acute myeloid leukemia without chromosomal abnormalities at 11q23. Leukemia 2002; 16: 196–202.

    Article  CAS  Google Scholar 

  24. Schnittger S, Kinkelin U, Schoch C, Heinecke A, Haase D, Haferlach T et al. Screening for MLL tandem duplication in 387 unselected patients with AML identify a prognostically unfavorable subset of AML. Leukemia 2000; 14: 796–804.

    Article  CAS  Google Scholar 

  25. Caligiuri MA, Strout MP, Oberkircher AR, Yu F, de la Chapelle A, Bloomfield CD . The partial tandem duplication of ALL1 in acute myeloid leukemia with normal cytogenetics or trisomy 11 is restricted to one chromosome. Proc Natl Acad Sci USA 1997; 94: 3899–3902.

    Article  CAS  Google Scholar 

  26. Schnittger S, Wormann B, Hiddemann W, Griesinger F . Partial tandem duplications of the MLL gene are detectable in peripheral blood and bone marrow of nearly all healthy donors. Blood 1998; 92: 1728–1734.

    CAS  PubMed  Google Scholar 

  27. Dorrance AM, Liu S, Chong A, Pulley B, Nemer D, Guimond M et al. The Mll partial tandem duplication: differential, tissue-specific activity in the presence or absence of the wild-type allele. Blood 2008; 112: 2508–2511.

    Article  CAS  Google Scholar 

  28. Whitman SP, Hackanson B, Liyanarachchi S, Liu S, Rush LJ, Maharry K et al. DNA hypermethylation and epigenetic silencing of the tumor suppressor gene, SLC5A8, in acute myeloid leukemia with the MLL partial tandem duplication. Blood 2008; 112: 2013–2016.

    Article  CAS  Google Scholar 

  29. de Souza Fernandez T, Menezes de Souza J, Macedo Silva ML, Tabak D, Abdelhay E . Correlation of N-ras point mutations with specific chromosomal abnormalities in primary myelodysplastic syndrome. Leuk Res 1998; 22: 125–134.

    Article  CAS  Google Scholar 

  30. Langabeer SE, Beghini A, Larizza L . AML with t(8;21) and trisomy 4: possible involvement of c-kit? Leukemia 2003; 17: 1915; author reply 1915–1916.

    Article  CAS  Google Scholar 

  31. Bacher U, Haferlach T, Kern W, Weiss T, Schnittger S, Haferlach C . The impact of cytomorphology, cytogenetics, molecular genetics, and immunophenotyping in a comprehensive diagnostic workup of myelodysplastic syndromes. Cancer 2009; 115: 4524–4532.

    Article  Google Scholar 

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Acknowledgements

We thank Dr Hwei-Fang Tien and her assistant Shau-Chi at the National Taiwan University Hospital, Taipei, Taiwan for the technical support in MLL PTD study using genomic DNA PCR.

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Authors and Affiliations

  1. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    S A Wang, K Jabbar, G Lu, S S Chen, F Vega, D Jones, T J McDonnell & L J Medeiros

  2. Department of Internal Medicine, St Vincent's Comprehensive Cancer Center, New York, NY, USA

    N Galili & A Raza

  3. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    H Kantarjian & G Garcia-Manero

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  1. S A Wang
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Correspondence to S A Wang.

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Wang, S., Jabbar, K., Lu, G. et al. Trisomy 11 in myelodysplastic syndromes defines a unique group of disease with aggressive clinicopathologic features. Leukemia 24, 740–747 (2010). https://doi.org/10.1038/leu.2009.289

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