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J Cancer Metastasis Treat 2019;5:5 I http://dx.doi.org/10.20517/2394-4722.2018.108 Page 25 of 27
16 Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano 20089, Italy.
17 Hematology, Ospedale degli Infermi, Rimini 47923, Italy.
18 Lymphoma Unit, Department of Onco-Haematology, IRCCS San Raffaele Scientific Institute, Milano 20132,
Italy.
19 Department of Hematology, Ospedale Generale, Bolzano 39100, Italy.
20 Oncology Unit, Humanitas/Gavazzeni Clinic, Bergamo 24125, Italy.
21 SC Ematologia, Azienda Ospedaliera Santi Antonio e Biagio e Cesare Arrigo, Alessandria 15121, Italy.

Introduction: In recent years, the outcome of mantle cell lymphoma (MCL) has improved, especially
in younger patients, receiving cytarabine-containing chemoimmunotherapy and autologous stem cell
transplantation. Nevertheless, a proportion of MCL patients still experience early failure. The aims of the
study are to identify biomarkers anticipating failure of intensive chemotherapy in MCL.

Experimental model: We performed target resequencing and DNA profiling of purified tumor samples
collected from patients enrolled in the prospective FIL-MCL0208 phase III trial (NCT02354313, high-dose
chemoimmunotherapy followed by autologous transplantation and randomized lenalidomide maintenance).

Results: Mutations of KMT2D and disruption of TP53 by deletion or mutation associated with an increased
risk of progression and death, both in univariate and multivariate analysis. By adding KMT2D mutations
and TP53 disruption to the MIPI-c backbone, we derived a new prognostic index, the “MIPI-genetic”. The
“MIPI-g” improved the model discrimination ability compared to the MIPI-c alone, defining three risk
groups: (1) low-risk patients (4-year PFS and OS of 72.0% and 94.5%); (2) intermediate-risk patients (4-year
PFS and OS of 42.2% and 65.8%); and (3) high-risk patients (4-year PFS and OS of 11.5% and 44.9%).

Conclusion: Our results: (1) confirm that TP53 disruption identifies a high-risk population characterized by
poor sensitivity to conventional or intensified chemotherapy; (2) provide the pivotal evidence that patients
harboring KMT2D mutations share the same poor outcome as patients harboring TP53 disruption; and (3)
allow to develop a tool for the identification of high-risk MCL patients for whom novel therapeutic strategies
need to be investigated.

34. In vitro and in vivo activity of biomimetic magnetic nanoparticles for drug delivery in
presence of gradient magnetic field

2
1
1
1
Maria Prat , Francesca Oltolina , Ana Peigneux Navarro , Donato Colangelo , Concepcion
Jimenez-Lopez 2
1 Laboratory of Histology, Department of Health Sciences, Università del Piemonte Orientale “A. Avogadro”,
Novara 28100, Italy.
2 Departamento de Microbiología, Facultad de Ciencias, Universidad de Granada, Fuentenueva, Granada
18071, Spain.

Nanotechnology and nanoparticles (NPs) have become very attractive for their applications in different
fields, comprising biology, medicine and oncology. In this context, magnetite nanoparticles are even
more interesting as they can be manipulated by an external magnetic field, besides being multifunctional
platforms.

Herein, we describe a drug delivery system based on biomimetic magnetic nanoparticles (BMNPs)
synthetized in presence of MamC protein from Magnetococcus marinus MC-1. MamC controls the