Project 2
Validation of the oncogenic SEPT6-ABL2 fusion
role in T-cell lymphoblastic neoplasms.
T-cell lymphoblastic neoplasms (T-ALL/LBL) are a type of aggressive hematological cancer derived from immature
T-cells, mostly affecting children and adolescent boys1. Treatment with multiple high-dose chemotherapy has
proven to be highly effective, but not infallible, due to acute and long-term toxicity and poor prognosis in
case of relapse2,3. With the ultimate goal of implementing personalized and precision medicine, our team is
analyzing molecular-genetic alterations in T-ALL/LBL patients; in a T-ALL patient at IIS-FJD who did not
overcome the disease with conventional treatment and who, unfortunately, died in 2020, we have found a novel
oncogenic fusion: SEPT6-ABL2. The hypothesis that this would be an hyperactive tyrosine kinase capable of
driving tumor transformation further suggests that the patient would have benefited from targeted treatment
using tyrosine kinase inhibitors (TKIs) such as imatinib and its derivatives; these drugs are approved for the
treatment of certain malignancies, such as Philadelphia-positive leukemias (Ph+-CML, Ph+-ALL), but not for
T-ALL/LBL. We have established a cell line derived from a tumor biopsy of the patient, which we will use as a
model to demonstrate whether the SEPT6-ABL2 fusion is a driver oncogenic alteration, as well as to reveal the
molecular mechanisms whereby it promotes tumor development. If our hypothesis is validated, we will propose
that the presence in T-ALL/LBL patients of ABL-involving fusions, such as this novel SEPT6-ABL2 fusion, would
serve as an argument to recommend their treatment with TKIs, thus contributing to improve their prognosis.
