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Cryptic ins(2;11) with clonal evolution showing amplification of 11q23–q25 either on hsr(11) or on dmin, in a patient with AML-M2

Leukemia volume 18, pages 2041–2044 (2004)Cite this article

TO THE EDITOR

Genomic amplification is a frequent aberration in malignant proliferation that usually leads to an inappropriate expression of one or more oncogenes located within the amplicon. Cytogenetically, it appears like homogeneously staining regions (hsr) or double minute chromosomes (dmin). In contrast to solid tumors, genomic amplification is rarely detected in hematological malignancies. The estimated incidence of cytogenetically detectable gene amplification in acute myeloid leukemia (AML) is approximately 1%. Recently, 11q23 over-representation has been described as a new cytogenetic entity in myeloid malignancies, and in these cases, the MLL gene (11q23) was consistently amplified. The oncogenic role of amplification in myeloid malignancies has not been demonstrated so far, although duplication or amplification of the MLL gene in t-AML has been significantly associated with complex karyotypes, deletion 5q, and prior therapy with alkylating agents.1 Van Limbergen et al2 found MLL amplification together with 5q- only in AML patients, and that was significantly associated with an extremely short survival. In most cases, the 11q23 amplified region includes the MLL gene (11q23.3), although is not restricted to this locus. Several studies using FISH or other molecular techniques in patients with myeloid neoplasias (10 cases with AML, and seven cases with MDS), have allowed the identification of the genes included in the amplified region as dmin and/or hsr such FGF3 (11q13.1), THRSP (11q13.5), DDX6 (11q23.3), ETS1 (11q24.3) and FLI1 (11q24.3).1, 3, 4, 5 Only three cases (two AML and one MDS) have been reported to have amplification of the 11q23–24 region not including the MLL gene.6, 7 Moreover, Zatkova et al5 found that deletions within the amplicon 11q13–24 were a quite common event (four out of 13 patients analyzed), suggesting that duplications and inversions affecting the 11q arm might play a role in the highly complex variability nature of the 11q amplicons, and that other genes with possible oncogenic potential role might be implicated in the amplification of this region. Here, we report the clinical, cytogenetic and molecular data of a patient with AML-M2 which presented a cryptic ins(2;11)(q3?6;q23.3) with a clonal evolution to 11q23–q25 amplification, either on hsr(11) or on dmin, in two divergent clones. The patient had the insertion in all clones, even in the one with no 11q amplification, suggesting that this rearrangement might play a role in the leukemogenic progression, and in the amplification process.

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Acknowledgements

This work was supported by Fundación Científica de la Asociación Española contra el Cáncer; Departamento de Salud y de Educación del Gobierno de Navarra; Fundación Internacional José Carreras (FIJC-03/ESP); Fundación para la Investigación Médica Aplicada y UTE; RTIC Cancer C10/03 (FIS) (Spain).

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Authors and Affiliations

  1. Department of Genetics, School of Science, University of Navarra, Pamplona, Spain

    I Vazquez, M J Larrayoz, J L Vizmanos, M J Calasanz & M D Odero

  2. Division of Oncology, School of Medicine, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain

    I Vazquez, I Lahortiga, X Agirre & M D Odero

  3. Department of Hematology, Hospital Txagorritxu, Vitoria, Spain

    M T Ardanaz

  4. Cardinal Bernardin Cancer Center, Loyola University, Maywood, IL, USA

    N J Zeleznik-Le

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  1. I Vazquez
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Correspondence to M D Odero.

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Vazquez, I., Lahortiga, I., Agirre, X. et al. Cryptic ins(2;11) with clonal evolution showing amplification of 11q23–q25 either on hsr(11) or on dmin, in a patient with AML-M2. Leukemia 18, 2041–2044 (2004). https://doi.org/10.1038/sj.leu.2403535

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