Genomic and trascriptomic analyses of pediatric T-cell lynphoblastic leukemia/limphoma

In the first part of our work we focused our attention on the biological question about the differences between two pathologies: T-cell lymphoblastic leukemia and T-cell lymphoblastic lymphoma. These two diseases share many features such as immunophenotypic features, lymphoblast morphology and clinical characteristics and are differentially diagnosed only on the base of bone marrow involvement. We tried to understand whether T-cell leukemia and lymphoma are a unique pathology with a different manifestation or whether they are two different diseases. The results obtained by gene expression profiling revealed an intrinsic difference in the expression of 78 genes between T-ALL and T-LBL. In particular since these genes belong to the angiogenesis and the chemotactic response we supposed that the two malignancies have different ability to respond to several cyto- and chemokines and that T-LBL need to modulate transcription to promote angiogenesis as well as to deal with hypoxic conditions. Also by analysis of copy number we were able to identify some abnormalities that seemed to be specific for each group regardless the limited data set of patients. Although this work provides additional elements in the characterization of these two pathologies, many studies have yet to be done, especially on the comprehension of the different capability of cells to migrate and invade the bone marrow compartment. The complete understanding of the molecular characteristics of T-LBL and T-ALL represents the driving element toward the design of fully successful therapeutic approaches. The second part of the study focused on the genetic characterization of two different groups of T-ALL patients on the basis of MRD response. With the aim to find biological correlates with the outcome for HR and nonHR patients, we performed many analyses, starting from copy number analysis to microRNAs expression profiling. Furthermore, we tried to integrate all the data in order to delineate common c