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MLL partner genes drive distinct gene expression profiles and genomic alterations in pediatric acute myeloid leukemia: an AIEOP study

Leukemia volume 25, pages 560–563 (2011)Cite this article

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Childhood acute myeloid leukemia (AML) is a heterogeneous disease with an overall poorer outcome as compared with acute lymphoid leukemia. Marked differences in terms of outcome of AML patients have been confirmed to be related to the presence of specific genetic aberrations.1 A subset of high-risk AML patients is characterized by rearrangements, involving the mixed-lineage leukemia gene (MLL) located on chromosome 11q23. More than 40 different translocation fusion partners of MLL have been identified in AML at diagnosis; however, five partner genes account for over 90% of MLL-translocated pediatric AML (AF9, AF10, AF6, ENL and ELL).2 Recently, Balgobind et al.3 published results from a collaborative international study group describing different clinical outcomes for MLL-11q23 translocation partner genes.

Finally, we showed that the MLL-AML is a heterogeneous leukemia depending on the MLL partner gene for GEP and cytogenetic analysis, with novel features for each subgroup of patients. The aggressive behavior mediated by the MLL/AF6 chimeric gene calls for in-depth investigation of its functional role in order to identify more effective therapy. The MLL/AF6-positive patients showed the highest frequency of genomic imbalances along with new target genes aberrantly expressed, which require further study. We also described here for the first time that del(12p) influences the outcome of MLL–AML, in particular in t(6;11)-positive cases. The use of a-CGH in AML–MLL revealed that genomic gains were found more frequently than losses, suggesting a general role of proto-oncogene activation in this leukemia. The observation that 6 out of 39 patients had the del(12p) suggested a possible association between the del(12p) and pediatric MLL-rearranged AML (15.5% in comparison with 3.7%, recently described in a large overall AML cohort8, 9). The finding that MLL–AML encompasses distinct biological and clinical diseases within the high-risk forms of pediatric AML forces reconsideration of these patients for distinct, specific therapies.

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Acknowledgements

This study was supported by grants from the Fondazione Città della Speranza-Padova-Italy (to MP, GB, AZ, SB and LT), from AIRC (Associazione Italiana Ricerca sul Cancro, to GB and GteK), from PRIN/Programmi di ricerca di Rilevante Interesse Nazionale, Rome (to GteK, GB), and the Ministero della Salute (to GB, GteK). We thank MariaGrazia Giacometti and Silvia Disarò for sample collection; Dr Laura Sainati and Dr Samuela Francescato for morphology evaluation; Nancy Jenkins for paper editing.

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Authors and Affiliations

  1. Department of Pediatrics, Laboratory of Hematology-Oncology, University of Padova, Padova, Italy

    M Pigazzi, S Bresolin, A Beghin, A Di Meglio, S Gelain, L Trentin, E Baron, M Giordan, A Zangrando, B Buldini, A Leszl, M C Putti, G Te Kronnie & G Basso

  2. Department of Pediatrics, ‘Lalla Seràgnoli’, Hematology-Oncology Unit, Ospedale Sant’Orsola, University of Bologna, Bologna, Italy

    R Masetti & A Pession

  3. Department of Pediatrics, Hematology-Oncology Unit, University of Milano-Bicocca, Hospital S. Gerardo, Monza, Italy

    C Rizzari

  4. Onco-hematology Department, IRCCS Ospedale Bambino Gesu,

    F Locatelli

  5. ′,

    F Locatelli

  6. , Roma, University of Pavia, Rome, Italy

    F Locatelli

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  1. M Pigazzi
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  9. M Giordan
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  13. M C Putti
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  16. A Pession
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Correspondence to M Pigazzi.

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Pigazzi, M., Masetti, R., Bresolin, S. et al. MLL partner genes drive distinct gene expression profiles and genomic alterations in pediatric acute myeloid leukemia: an AIEOP study. Leukemia 25, 560–563 (2011). https://doi.org/10.1038/leu.2010.316

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