Andrea Biondi - Full Professor
Department and institution: Department of Health Sciences, School of Medicine and Surgery, University of Milano Bicocca
tel. +39 02 6448 8055
institutional profile page: UNIMIB
see also: BOA, PudMed
Keywords : Childhood leukemia, leukemia stem cells, targeted therapy, bone marrow transplantation, graft versus host disease
Molecular dissection of the etiopathogenesis of childhood Acute Lymphoblastic Leukemia (ALL)
(P.I.: G.Cazzaniga, PhD)
Acute Lymphoblastic Leukemia (ALL) is the most common type of childhood leukemia and the most frequent malignancy in children, representing one third of all pediatric cancers. Leukemia is a multistep process: it starts from a first pre-natal genetic event (frequently a chromosomal translocation) in a precursor cell, and the accumulation of cooperative genetic events lead to the full transformation and clinical onset. Different genetic events are responsible of a large biological heterogeneity and are associated to different patients’ outcome. The understanding of the altered cellular pathways is the key to develop new drugs specifically directed to leukemic cells, to be associated with the ongoing standard multi-chemotherapy with the aim to increase efficacy and reduce long term toxic side effects. The major known targets are genes encoding for transcription factors critical for stem cell development and hematopoietic lineage definition (i.e. MLL, TEL/ETV6, Ikaros, PAX5/BSAP) or tyrosine kinases (i.e. ABL, PDGFR).
Main topics of the group
- The pre-leukemic state of the TEL/AML1 positive cell;
- Functional characterization of PAX5 genomic lesions;
- Characterization of the “leukemia-initiating stem cell(s)” in Infant ALL with t(4;11);
- Dissection of cell pathways in high risk leukemia, and testing of novel drugs
Scientific bases for improving the cure of leukemic patients experiencing severe post-transplant Graft-versus-Host Disease: identification of new molecular targets and disease biomarkers
(P.I.: G.D’Amico, PhD)
Allogeneic hemopoietic-stem-cell transplantation (HSCT) is the treatment of choice for many malignant and non-malignant paediatric disorders, such as immune deficiencies and metabolic defects. Despite advances in donor HLA typing methods (and thus donor selection) and post transplant immune suppression, graft-versus-host disease (GvHD) remains a significant cause of transplant-related mortality and morbidity following allogeneic HSCT. The further increase in the cure rates can be approached by improving HSCT outcome. We believe that this crucial objective could be reached by providing scientific bases for novel and better protocols for managing steroid-resistant GVHD. Along these hypotheses, the project comprises two lines of research:
i) Identification of new easily measurable GVHD biomarkers. This line of research will focus on the study of the acute phase protein, long pentraxin 3 (PTX3), which is locally produced at sites of inflammation. We recently observed increased PTX3 levels in the plasma of HSCT patients before the occurrence and at the onset of GVHD. If these data will be confirmed, PTX3 would represent a crucial marker to predict GVHD onset and to follow patient response to therapy.
ii) Development of innovative highly specific anti-GVHD treatments. A better understanding of GVHD pathogenesis can lead to the development of innovative therapeutic strategies. In particular, the identification of the molecular mechanisms involved in controlling the expression of chemokines and their receptors in GVHD may provide efficient strategies to improve disease management.
Selected Recent Publications
Cazzaniga, G., De Lorenzo, P., Alten, J., Röttgers, S., Hancock, J., Saha, V., et al. (2018).
Predictive value of minimal residual disease in philadelphia-chromosome-positive acute lymphoblastic leukemia treated with imatinib in the European intergroup study of post-induction treatment of Philadelphia-chromosome-positive acute lymphoblastic leukemia, based on immunoglobulin/T-cell receptor and BCR/ABL1 methodologies.
HAEMATOLOGICA, 103(1), 107-115. MORE
Schrappe, M., Bleckmann, K., Zimmermann, M., Biondi, A., Möricke, A., Locatelli, F., et al. (2018).
Reduced-Intensity delayed intensification in standard-Risk pediatric acute lymphoblastic leukemia defined by undetectable minimal residual disease: Results of an international randomized trial (AIEOP-BFM ALL 2000).
JOURNAL OF CLINICAL ONCOLOGY, 36(3), 244-253. MORE
Stanulla, M., Dagdan, E., Zaliova, M., Möricke, A., Palmi, C., Cazzaniga, G., et al. (2018).
IKZF1plusDefines a New Minimal Residual Disease-Dependent Very-Poor Prognostic Profile in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia.
JOURNAL OF CLINICAL ONCOLOGY. MORE
Manara, E., Basso, G., Zampini, M., Buldini, B., Tregnago, C., Rondelli, E.R., et al. (2017).
Characterization of children with FLT3-ITD acute myeloid leukemia: A report from the AIEOP AML-2002 study group.
LEUKEMIA, 31(1), 18-25. MORE
Pievani, A., Sacchetti, B., Corsi, A., Rambaldi, B., Donsante, S., Scagliotti, V., et al. (2017).
Human umbilical cord blood-borne fibroblasts contain marrow niche precursors that form a bone/marrow organoid in vivo.
DEVELOPMENT, 144(6), 1035-1044. MORE