The Giulio Superti-Furga lab has a long-standing interest in understanding the molecular wiring of transformed cells of the hematopoietic system as well as studying the mode of action of targeted agents counteracting leukemia cell proliferation. Starting from BCR-ABL signaling in Chronic myeloid leukemia (CML) to different types of Acute myeloid leukemia (AML) as model system, we are using advanced genetic screening systems (shRNAmiR, haploid genetic screening, CRISPR/Cas9) as well as mass spectrometry based proteomics to uncover novel therapeutic avenues and mechanisms of resistance towards targeted therapy.
MLL rearranged leukemia is an aggressive blood cancer that occurs especially in pediatric patients. The MLL gene is essential for normal development and MLL rearrangements can be found in 10% of human acute leukemias. Current treatment options are limited to chemotherapy and allogeneic hematopoietic stem cell transplantation. However, due to severe side effects the outcome remains poor. MLL is a part of a large, nuclear complex that comprises many proteins crucial for targeting and activity of MLL. Even though critical effectors of distinct fusion proteins have been identified, the molecular mechanism of transformation remains unknown for majority of them. We hypothesize that AML and different MLL fusion proteins share critical effectors and therefore common oncogenic mechanisms exist. We are currently identifying critical, common effectors of oncogenic mechanisms in AML in a systematic manner using a unique experimental pipeline developed in-house.