This multicenter translational study, with prospective and retrospective samples, aims to identify new strategies to selectively eliminate neoplastic T cells by modulating intracellular ROS levels.

Interactions between drugs capable of activating the apoptotic process (e.g., Venetoclax) and drugs capable of altering ROS homeostasis (e.g., inhibitors of the enzyme glucose-6-phosphate dehydrogenase) will be examined.

The most promising compounds will be selected based on results obtained in vitro on cell lines and PDX already available in the laboratory, and then will be assayed ex vivo in cells obtained from patients with resistant/refractory T-cell neoplasms.

Inclusion Criteria:

• Patients with pre- and post-thymic T-cell leukemia/lymphoma
• Patients of both sexes
• Age of patients older than 18 years
• Patient is willing to provide written and signed informed consent for participation in the study

Exclusion Criteria:

-Serious illness or medical condition that does not allow the patient to be managed according to standard treatment protocols, including uncontrolled active infection.

Up to a maximum of 120 patients (both retrospective and prospective) are expected to be enrolled during the study period. Specifically, a maximum of 40 patients will be enrolled for each of the following diseases: T-cell lymphoblastic leukemias (T-ALL); T-cell non-Hodgkin lymphomas (T-NHL); NK-cell neoplasms. For retrospective peripheral blood samples, bone marrow aspirates, and lymph node biopsies, which are available at the centers involved in the study, patients will be contacted again to ask for consent regarding this project.

No additional clinical procedures are specifically required by participation in the present study. In fact, samples will be obtained from the material left over from samples taken for clinical procedures.