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Acute Non-Lymphocytic Leukemias

Characterization of a recurrent translocation t(2;3)(p15–22;q26) occurring in acute myeloid leukaemia

Leukemia volume 20, pages 48–54 (2006)Cite this article

A Corrigendum to this article was published on 24 May 2006

Abstract

Six patients with de novo acute myeloid leukemia (AML) and a t(2;3)(p15–21;q26–27) were identified among approximately 1000 cases enrolled in the GIMEMA trial. The t(2;3) was the sole anomaly in three patients, whereas in three cases monosomy 7, trisomy 15 and 22, and trisomy 14 represented additional aberrations. No cryptic chromosome deletions at 5q, 7q, 12p, and 20q were observed. One patient carried a FLT3 D835 mutation; FLT3 internal tandem duplication (ITD) was not detected in three patients tested. Characterization of the translocation breakpoints using a 3q26 BAC contig specific for the PRDM3 locus showed that the breakpoints were located 5′ to EVI1 as follows: within myelodysplatic syndrome (MDS) intron 1 (# 3), between MDS1 exons 2 and 3 in three patients (# 1, 2, 4) with a 170 bp cryptic deletion distal to the breakpoint in one (# 2), and in a more centromeric position spanning from intron 2 to the 5′ region of EVI1 (# 6, 5). A set of 2p16–21 BAC probes showed that the breakpoints on chromosome 2p were located within BCL11A in two separate regions (# 1, 4 and # 2–5), within the thyroid adenoma-associated (THADA) gene (# 6) or distal to the ZFP36L2 locus (# 3). Regulatory elements were present in proximity of these breakpoints. RACE PCR studies revealed a chimeric transcript in 1/6 patient analyzed, but no fusion protein. Quantitative PCR showed a 21–58-fold overexpression of the EVI1 gene in all cases analyzed. The patients showed dysplasia of at least two myeloid cell lineages in all cases; they had a low-to-normal platelet count and displayed an immature CD34+ CD117+ immunophenotype. Despite intensive chemotherapy and a median age of 43 years (range 36–59), only two patients attained a short-lived response; one patient is alive with active disease at 12 months, five died at 4–14 months. We arrived at the following conclusions: (a) the t(2;3) is a recurrent translocation having an approximate 0.5% incidence in adult AML; (b) breakpoints involve the 5′ region of EVI1 at 3q26, and the BCL11A, the THADA gene or other regions at 2p16.1–21; (c) cryptic deletions distal to the 3q26 breakpoint may occur in some cases; (d) the juxtaposition of the 5′ region of EVI1 with regulatory elements normally located on chromosome 2 brings about EVI1 overexpression; (e) clinical outcome in these cases is severe.

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Acknowledgements

Work in our laboratories was supported by FIRB- MIUR, PRIN-MIUR, fondi 60%, AIRC (Associazione Italiana Ricerca sul Cancro), CNR, Rome.

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Authors and Affiliations

  1. IFOM, Milan, Italy

    M Trubia & P G Pelicci

  2. Dipartimento di Oncologia Sperimentale, Istituto Europeo di Oncologia, Milano, Italy

    M Trubia & P G Pelicci

  3. Cattedra di Ematologia, Università di Bari, Bari, Italy

    F Albano, G Specchia & V Liso

  4. Sezione di Ematologia DSBTA, Università di Ferrara, Ferrara, Italy

    F Cavazzini, G Castoldi & A Cuneo

  5. Medicina Interna II, Ospedale S Luigi Gonzaga di Orbassano, Università di Torino, Torino, Italy

    G R Cambrin

  6. Divisione di Ematologia Ospedale “Perrino” Brindisi, Brindisi, Italy

    G Quarta

  7. Ospedale ‘Cervello’, Palermo, Palermo, Italy

    F Fabbiano

  8. UO Ematologia Ospedale di Gallarate, Gallarate, Italy

    F Ciambelli

  9. UO di Ematologia Ospedale di Catanzaro, Catanzaro, Italy

    D Magro

  10. Servicio de Hematologia, Hospital Universitario de Salamanca & Centro de Investigacion del Cancer (CIC), Salamanca, Spain

    J M Hernandez

  11. Istituto di Ematologia, Università ‘La Sapienza’, Roma, Italy

    M Mancini & D Diverio

  12. Dipartimento di Medicina, Chirurgia ed Odontoiatria, Universita' degli Studi di Milano, Milan, Italy

    P G Pelicci

  13. Istituto di Ematologia, Università ‘Tor Vergata’, Roma, Italy

    F L Coco

  14. Istituto di Ematologia, Università di Perugia, Perugia, Italy

    C Mecucci

  15. Dipartimento di Genetica e Microbiologia (DI. GE. MI), University of Bari, Bari, Italy

    M Rocchi

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  1. M Trubia
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Correspondence to A Cuneo.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu).

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Trubia, M., Albano, F., Cavazzini, F. et al. Characterization of a recurrent translocation t(2;3)(p15–22;q26) occurring in acute myeloid leukaemia. Leukemia 20, 48–54 (2006). https://doi.org/10.1038/sj.leu.2404020

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