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. 2017 Jan;31(1):18-25.
doi: 10.1038/leu.2016.177. Epub 2016 Jun 28.

Characterization of children with FLT3-ITD acute myeloid leukemia: a report from the AIEOP AML-2002 study group

E Manara  1 , G Basso  2 , M Zampini  1 , B Buldini  2 , C Tregnago  2 , R Rondelli  3 , R Masetti  3 , V Bisio  2 , M Frison  2 , K Polato  2 , G Cazzaniga  4 , G Menna  5 , F Fagioli  6 , P Merli  7 , A Biondi  4 , A Pession  3 , F Locatelli  7 , M Pigazzi  2
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Characterization of children with FLT3-ITD acute myeloid leukemia: a report from the AIEOP AML-2002 study group

E Manara et al. Leukemia. 2017 Jan.

Abstract

Recurrent molecular markers have been routinely used in acute myeloid leukemia (AML) for risk assessment at diagnosis, whereas their post-induction monitoring still represents a debated issue. We evaluated the prognostic value and biological impact of minimal residual disease (MRD) and of the allelic ratio (AR) of FLT3-internal-tandem duplication (ITD) in childhood AML. We retrospectively screened 494 children with de novo AML for FLT3-ITD mutation, identifying 54 harboring the mutation; 51% of them presented high ITD-AR at diagnosis and had worse event-free survival (EFS, 19.2 versus 63.5% for low ITD-AR, <0.05). Forty-one percent of children with high levels of MRD after the 1st induction course, measured by a patient-specific real-time-PCR, had worse EFS (22.2 versus 59.4% in low-MRD patients, P<0.05). Next, we correlated these parameters with gene expression, showing that patients with high ITD-AR or persistent MRD had characteristic expression profiles with deregulated genes involved in methylation and acetylation. Moreover, patients with high CyclinA1 expression presented an unfavorable EFS (20.3 versus 51.2% in low CyclinA1 group, P<0.01). Our results suggest that ITD-AR levels and molecular MRD should be considered in planning clinical management of FLT3-ITD patients. Different transcriptional activation of epigenetic and oncogenic profiles may explain variability in outcome among these patients, for whom novel therapeutic approaches are desirable.

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References

    1. Oncogene. 2004 Dec 2;23(56):9082-9 - PubMed
    1. Clin Cancer Res. 2004 Aug 1;10 (15):4991-7 - PubMed
    1. J Clin Oncol. 2015 Sep 20;33(27):2949-62 - PubMed
    1. Curr Mol Med. 2012 Jan;12(1):27-33 - PubMed
    1. Cell Rep. 2015 Aug 4;12(5):821-36 - PubMed

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