Direct integrative single-cell sequencing of Acute Lymphoblastic Leukemia patients
Leukemia is a complex disease caused by the accumulation of oncogenic lesions in developing lymphoid cells. This hematologic malignancy shows extensive genetic intra-tumoral heterogeneity. However, we still do not fully understand how it develops, the exact type of cells that compose it and the sensitivity of the different cells to the treatment. In order to dissect heterogeneity, it is essential to perform studies with single-cell resolution. In this project we aim to provide a highresolution single-cell view of leukemia development and the response to treatment directly from patient samples. We will investigate two molecular dimensions of the same cell, DNA and RNA, in thousands of leukemic cells per patient and at different timepoints. With this, we expect to determine whether the level of heterogeneity can be linked with prognosis and to identify subclones (potentially with novel mutations) correlating with drug resistance and contributing to the development of relapse. Ultimately, the results of this project will have implications in risk stratification and future personalized medicine based on individualized patient’s molecular profiles.