FRRB 2015-042 - Genomic profiling of rare hematologic malignancies, development of personalized medicine strategies, and their implementation into the Rete Ematologica Lombarda (REL) clinical network

Pathology of interest:

Rare hematologic malignacies

Area of research:

Immunology and Infection

Start date:

May 2017

End date:

October 2020


€ 4.166.400

Project partners:

Fondazione IRCCS Policlinico San Matteo – leading partner

ASST dei Sette Laghi - Varese

ASST Papa Giovanni XXIII - Bergamo

IRCCS Humanitas Mirasole

ASST Ospedale Metropolitano Niguarda - Milano

Università degli Studi di Pavia

Novartis Farma Spa

Celgene Srl

Clonit Srl


The project studies rare hematologic diseases that affect less than 0.05% of the population, which means less than 5 people every 10,000 individuals. Most tumors of hematopoietic and lymphoid tissues belong to this category, including myelodysplastic syndromes, myeloproliferative neoplasms, myelodysplastic/myeloproliferative neoplasms, acute myeloid leukemia and classical Hodgkin lymphoma. Any of these disorders includes at least a subset of patients with poor clinical outcome and significant unmet medical needs.

The project aims at defining new personalized medicine approaches that can be implemented into the "Rete Ematologica Lombarda", REL, which is a regional network of institutions involved in the study and the cure of hematological malignancies. 


The projects is divided in 5 Action:

  • Action 1. Genetic basis and advanced disease models in myeloid malignancies;
  • Action 2. Genomic profiling to guide treatment of myeloid malignancies;
  • Action 3. Molecular mechanisms of therapy resistance in hematologic malignancies;
  • Action 4. Innovative cellular therapies for rare hematologic malignancies;
  • Action 5. Design and implementation of a bioinformatics system for the analysis and integration of clinical and biological data to support translational research in hematology oncology.


Title Journal Year IF
Gender effect on phenotype and genotype in patients with post-polycythemia vera and post-essential thrombocythemia myelofibrosis: results from the MYSEC project Blood Cancer Journal 2018 7,90
Cord blood-derived cytokine-induced killer cells combined with blinatumomab as a therapeutic strategy for CD19+ tumors Cytotherapy 2018 4,12
Targeting the CoREST complex with dual histone deacetylase and demethylase inhibitors Nature Communications 2018 11,88
Targeting Cancer Cells and Tumor Microenvironment in Preclinical and Clinical Models of Hodgkin Lymphoma Using the Dual PI3Kδ/γ Inhibitor RP6530 Clinical Cancer Research 2018 8,911
Chronic myeloproliferative neoplasms in the elderly European Journal of Internal Medicine 2018 4,80
Direct-Acting Antivirals in Hepatitis C Virus-Associated Diffuse Large B-cell Lymphomas The Oncologist 2018 5,25
Aberrant splicing and defective mRNA production induced by somatic spliceosome mutations in myelodysplasia Nature Communications 2018 11,88
Circulating tumor DNA reveals genetics, clonal evolution, and residual disease in classical Hodgkin lymphoma Blood Journal 2018 16,60
A phase Ib study to assess the efficacy and safety of vismodegib in combination with ì ruxolitinib in patients with intermediate- or high-risk myelofibrosis. Journal of Hematology & Oncology 2018 8,93
Deferasirox in the management of iron-overload in patients with myelofibrosis: a multicentre study from the Rete Ematologica Lombarda (IRON-M study)  British Journal of Haematology 2019 5,52
Developments in diagnosis and treatment of essential thrombocythemia Expert Review of Hematology 2019 2,57
Second primary malignancies in postpolycythemia vera and postessential thrombocythemia myelofibrosis: A study on 2233 patients Cancer Medicine 2019 3,49
Core Binding Factor Leukemia: Chromatin Remodeling Moves Towards Oncogenic Transcription Cancers 2019 6,126 
Clinical, histopathological and molecular characterization of hypoplastic myelodysplastic syndrome Leukemia 2019 8,80
Validation and further potentialities of the novel AWM score for progression risk stratification in patients with asymptomatic Waldenström macroglobulinemia Leukemia & Lymphoma 2019 2,97
Impact of bone marrow fibrosis grade in postpolycythemia vera and postessential thrombocythemia myelofibrosis: A study of the MYSEC group American Journal of Hematology 2019 6,52
Standard care and investigational drugs in the treatment of myelofibrosis Drugs in Context 2019 3,56
Second primary malignancies in ruxolitinib treated myelofibrosis: real-world evidence from 219 consecutive patients Blood Advances 2019 4,64
Molecular profiling and risk classification of patients with myeloproliferative neoplasms and splanchnic vein thromboses Blood Advances 2020 4,91
Targeted Next Generation Sequencing Reveals Molecular Heterogeneity in non-CLL Clonal B-Cell Lymphocytosis Hematological Oncology 2020 10,74
Defective interaction of mutant calreticulin and SOCE in megakaryocytes from patients with myeloproliferative neoplasms Blood 2020 17,54
A continuous-time Markov model approach for modeling myelodysplastic syndromes progression from cross-sectional data Journal of Biomedical Informatics 2020 3,53
Stem cell mobilization after bendamustine in indolent lymphomas: a multicenter study on behalf of the Fondazione Italiana Linfomi Bone Marrow Transplantation 2020 4,84
Direct-acting antivirals in relapsed or refractory hepatitis C virus-associated diffuse large B-cell lymphoma Leukemia & Lymphoma 2020 2,97
Combined Anti-Cancer Strategies Based on Anti-Checkpoint Inhibitor Antibodies Antibodies 2020 0,40
Key Features Defining the Disposition of Bispecific Antibodies and Their Efficacy In Vivo Therapeutic Drug Monitoring 2020 2,07
Integrated Multi-Omics Analyses in Oncology: A Review of Machine Learning Methods and Tools Frontiers in Oncology 2020 4,85
Tranylcypromine-Based LSD1 Inhibitors: Structure-Activity Relationships, Antiproliferative Effects in Leukemia, and Gene Target Modulation ChemMedChem 2020 3,12
Platelet Count Predicts Driver Mutations’ Co-1 Occurrence In Low Jak2 Platelet Count Predicts Driver Mutations’ Co-1 Occurrence In Low Jak2 Mutated Essential Thrombocythemia And Myelofibrosis Leukemia 2020 8,67
Clonal evolution patterns in patients with myelofibrosis undergoing allogenic hematopoietic stem cell transplantation Biology of Blood and Marrow Transplantation 2020 3,85
Sleeping Beauty-engineered CAR T cells achieve antileukemic activity without severe toxicities Journal of Clinical Investigation 2020 11,86
The Role of Complement in the Mechanism of Action of Therapeutic Anti-Cancer mAbs. Antibodies 2020 0,40
FZD6 triggers Wnt–signalling driven by WNT10BIVS1 expression and highlights new targets in Tcell acute lymphoblastic leukemia Hematological Oncology 2021 3,23
Mutational Lanscape of HCV-associated B-cell Lymphoproliferative Disorders Blood   Submitted  



Le sindromi mielodisplastiche (MDS), le neoplasie mieloproliferative (MPN) e MDS/MPN, la leucemia mieloide acuta e il linfoma di Hodgkin classico (LH) sono malattie ematologiche rare con profili prognostici eterogenei e con problematiche cliniche ancora aperte.

Il progetto mira a definire nuovi approcci di medicina personalizzata da implementare nella Rete Ematologica Lombarda (REL), un network regionale di studio e cura delle malattie ematologiche.

Le Unità coinvolte, grazie anche a prestazioni terze e collaborazioni internazionali, hanno raggiunto tutti gli obiettivi prefissati e hanno:

• sviluppato e standardizzato piattaforme molecolari

• identificato lesioni genetiche e studiato il loro ruolo nel definire le caratteristiche cliniche e la prognosi nelle neoplasie mieloidi

• sviluppato nuovi approcci terapeutici e modelli prognostici innovativi

• proposto nuovi modelli di sperimentazioni cliniche e avviato vari trials tra cui studi di fase I/II per l’uso di farmaci innovativi a target molecolare

• studiato l’utilità del DNA circolante e i meccanismi di resistenza molecolare nel LH

• usato terapie cellulari innovative: la piattaforma cellulare scelta (cellule CIK allogeniche) e il metodo di trasduzione genica (con trasposoni e senza bisogno di vettori virali) sono metodiche del tutto innovative

• disegnato e implementato un sistema bioinformatico per l’analisi e l’integrazione di dati clinici e biologici a supporto della ricerca traslazionale in oncoematologia

• ampliato la coorte REL di pazienti con neoplasia mieloide, di cui sono disponibili campioni biologici e dati clinici per futuri studi.

Alcune Unità hanno arricchito il progetto con studi inizialmente non previsti su alcune forme di neoplasie linfoidi.

I risultati ottenuti sono oggetto di 20 comunicazioni a congressi nazionali e internazionali, 4 capitoli in volumi e 48 pubblicazioni scientifiche su riviste internazionali indicizzate con impact factor totale pari a 330.