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Incidence and significance of cryptic chromosome aberrations detected by fluorescence in situ hybridization in acute myeloid leukemia with normal karyotype

Leukemia volume 16, pages 1745–1751 (2002)Cite this article

Abstract

To better define the incidence and significance of cryptic chromosome lesions in acute myeloid leukemia (AML), fluorescence in situ hybridization (FISH) studies were performed in interphase cells and, when appropriate, in metaphase cells and in morphologically intact BM smears. Fifty-five adult de novo AML (group A) and 27 elderly AML or AML after myelodysplastic syndrome (AML-MDS) (group B) were tested using probes detecting the following anomalies: −5, −7, +8, deletions of 5q31, 7q31, 12p13/ETV6, 17p13/p53, 20q11. All the patients had a normal karyotype in more than 20 cells and tested negative for the common AML-associated fusion genes. No patient in group A was found to carry occult chromosome anomalies, whereas 8/27 patients in group B (P < 0.0001) showed 5q31 or 7q31 deletion (three cases each), a 17p13/p53deletion or trisomy 8 (one case each) in 33–60% interphase cells. Metaphase cells showed only one hybridization signal at 5q31 (three cases) and 7q31 (one case), whereas two normal signals at 7q31 and chromosome 8 centromeres were seen in two patients with 7q deletion and trisomy 8 in interphase cells. The majority of blast cells (76–94%) carried the chromosome anomaly in all cases; erythroid involvement in a minority of cells was seen in three patients. In group B, the presence of occult chromosome anomalies was associated with exposure to myelotoxic agents in the workplace (5/8 cases vs 3/19, P = 0.026) and with a lower complete remission rate (0/6 patients vs 7/12, P = 0.024). We arrived at the following conclusions: (1) cryptic chromosome deletions in the order of a few hundred kb magnitude may be found in a fraction of elderly AML or MDS-related AML and not in de novo adult AML with normal karyotype; (2) these chromosome lesions are usually represented by submicroscopic rearrangements; (3) they display a specific pattern of cell-lineage involvement arguing in favor of their role in the outgrowth of the leukemic blast cells; (4) they are associated with a history of exposure to myelotoxic agents in the workplace and, possibly, with resistance to induction treatment.

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Acknowledgements

This work was supported by AIRC and AIL, by MURST 1999 ex 40% and 60%, by CNR. The authors thank the following physicians for referring BM samples for cytogenetic analysis: S Amadori (Rome), G Avanzi (Novara), P Bodini (Cremona), AM Carella (S Giovanni Rotondo), Epis (Sondrio), G Fioritoni (Pescara), A Gabbas (Nuoro), A Levis (Alessandria), M Longinotti (Sassari), R Mozzana (Gallarate), F Nobile (Reggio Calabria), A Peta (Catanzaro), M Petrini (Pisa), B Rotoli (Napoli), G Torelli (Modena), E Volpe (Avelllino).

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  1. Dipartimento di Scienze Biomediche e Terapie Avanzate - Sezione di Ematologia, University of Ferrara, Italy

    A Cuneo, R Bigoni, F Cavazzini, A Bardi, MG Roberti, P Agostini, E Tammiso, N Ciccone & G Castoldi

  2. Chair of Hematology, University ‘La Sapienza’, Rome, Italy

    M Mancini, M Nanni, R De Cuia, M Divona & F Lo Coco

  3. Institute of Hematology, University of Perugia, Italy

    R La Starza, B Crescenzi & C Mecucci

  4. Insitute of Hematology, University of Bologna, Italy

    N Testoni

  5. Institute of Internal Medicine, S Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy

    G Rege Cambrin & G Saglio

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Cuneo, A., Bigoni, R., Cavazzini, F. et al. Incidence and significance of cryptic chromosome aberrations detected by fluorescence in situ hybridization in acute myeloid leukemia with normal karyotype. Leukemia 16, 1745–1751 (2002). https://doi.org/10.1038/sj.leu.2402605

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