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.

Characterization of children with flt3-itd acute myeloid leukemia. a report from the aieop aml-2002 study group / Manara, E.; Basso, G.; Zampini, M.; Buldini, B.; Tregnago, C.; Rondelli, R.; Masetti, R.; Bisio, V.; Frison, M.; Polato, K.; Cazzaniga, G.; Menna, G.; Fagioli, F.; Merli, P.; Biondi, A.; Pession, A.; Locatelli, F.; Pigazzi, M.. - In: LEUKEMIA. - ISSN 0887-6924. - 31:1(2017), pp. 18-25. [10.1038/leu.2016.177]

Characterization of children with flt3-itd acute myeloid leukemia. a report from the aieop aml-2002 study group

Menna G.;Pession A.;Locatelli F.;
2017

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.
2017
internal tandem duplication; histone deacetylase inhibitor; acute myelogenous leukemia; minimal residual disease; induction therapy; risk group; cyclin a1; aml; cells; mutations
01 Pubblicazione su rivista::01a Articolo in rivista
Characterization of children with flt3-itd acute myeloid leukemia. a report from the aieop aml-2002 study group / Manara, E.; Basso, G.; Zampini, M.; Buldini, B.; Tregnago, C.; Rondelli, R.; Masetti, R.; Bisio, V.; Frison, M.; Polato, K.; Cazzaniga, G.; Menna, G.; Fagioli, F.; Merli, P.; Biondi, A.; Pession, A.; Locatelli, F.; Pigazzi, M.. - In: LEUKEMIA. - ISSN 0887-6924. - 31:1(2017), pp. 18-25. [10.1038/leu.2016.177]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1479606
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