Role of MEN1 in B cell acute lymphoblastic leukemia

B Cell Acute Lymphoblastic Leukemias is a heterogenous group of hematological disorder resulting in an impaired hematopoiesis because of an aberrant proliferation and blocked differentiation of immature lymphocytic cells, causing bone marrow failure. According to the type of driver mutation, different groups of B-ALL can be identified among which the most recurrent are the Philadelphia chromosome+ and KMT2A-rearrenged+ leukemias. The former is characterized by an altered tyrosine-kinase of the resulting fusion protein BCR-ABL by the aforementioned aberrant chromosome, whereas KMT2Ar+ malignancies are characterized by aberrant expression of HOX and MEIS1 transcription factors, as result of the interaction of MEN1 and the mutant KMT2A, fused to a translocation-gene partner. The advent of small molecular weight inhibitor on clinic for treatment of mutation-specific subgroup B-ALL, such as imatinib for BCR-ABL+ leukemias and MEN1/KMT2A inhibitor for KMT2Ar+ leukemias, improved the survival rate over conventional chemotherapeutic approaches but relapses might still be observed after remission and the search for a non-mutation specific approach is still needed. In this work, we aimed at investigating the role of MEN1 in different groups of B-ALL looking for novel therapeutic approaches. The interference of MEN1 expression, either via shRNA-mediated knockdown or CRISPr-Cas9 knockout, revealed in RS4;11 (KMT2A-AF4), Sup-b15 (BCR-ABL) and Nalm-6 (ETV6-PDGFRB) cytotoxic effects and impaired cell survival, providing us a new hint for a new strategy based on the complete degradation of MEN1 in leukemic cells.