Brunangelo Falini

In 2018, Falini's group analyzing the genome of thousands microdissected Hodgkin and Reed-Sternberg tumor cells discovered recurrent mutations of STAT3, STAT5B, JAK1, JAK2 and PTPN1 that support the pivotal role of aberrant activation of JAK-STAT signalling pathway in the molecular pathogenesis of Hodgkin lymphoma.

In 2012, Falini and colleagues discovered that the BRAF-V600E mutation represents the causal genetic event in HCL, triggering transformation through the constitutive activation of the RAF-MEK-ERK signaling pathway. Then, Falini's group went immediately from bench to bedside, establishing the first PCR diagnostic test for HCL and demonstrating the high clinical benefit of the BRAF inhibitor vemurafenib in heavily pre-treated refractory/relapsed HCL patients. More recently, Falini and colleagues reported that vemurafenib plus rituximab induces a durable complete response (often MRD negative) in most patients with refractory/relapsed HCL.

In 2011, using whole exome sequencing to further explore AML with normal karyotype, Falini led the team that first identified BCL6 co-repressor (BCOR) mutations as a new driver genetic lesion in AML and its association with DNMT3A mutations and with poor prognosis.

In 2005, stemming from his immunohistological studies on ALK-positive ALCL, Falini discovered that tumor cells from about one-third of adult AML (mostly carrying a normal cytogenetic) expressed aberrantly in the cytoplasm nucleophosmin (a nucleolar located protein). This finding prompted Falini and colleagues to sequence the NPM1 gene and to discover heterozygous mutations at exon 12, responsible for the aberrant nuclear export of the NPM1 mutant protein.

Falini serves as a member of the International Lymphoma Study Group (ILSG) and has been in the Clinical Advisory Committees for the WHO classification of lympho-hemopoietic tumors (2001, 2008 and 2017 versions). He has made discoveries in the field of acute myeloid leukemia (AML) and lymphomas, going from bench to bedside.

Falini also contributed to the development over time of modern classifications of lympho-hematopoietic neoplasms, including REAL (1994), WHO (2001), WHO (2008), and WHO (2017), that he all co-signed. Using monoclonal antibodies against ALK and NPM1, Falini and colleagues took major steps forward in the biological and clinical characterization of ALK-positive anaplastic large-cell lymphoma (ALCL) and in the identification of NPM1-mutated AML, greatly contributing to their inclusion, as new disease entities, in the WHO classification of lympho-hemopoietic neoplasms.

Falini received his M.D. degree in 1976, and completed his specialization in Internal Medicine at University of Perugia. He was Research Fellow at University of Southern California (1980-1981) working on the lymphoma classification and then in United Kingdom at John Radcliffe Hospital, Oxford (1982-1984) working on strategies for generating novel monoclonal antibodies against lymphoid-associated antigens.