Lymphoma is the third most common type of cancer among children and accounts for 10-15% of all childhood cancers. An unmet need is to understand the molecular and cellular pathophysiology to define better treatment for patients with pediatric lymphoma, both in the primary and relapse setting, and for poor prognosis lymphoma of primary immunodeficiency patients. Two studies from 2020 have performed single cell RNA expression analysis of adult follicular lymphoma and diffuse large B cell lymphoma cells and identified that the malignant lymphoma cells segregate into multiple coexisting subclones, characterized by differential protein expression, calling for personalized treatment strategies. Single cell analysis of pediatric lymphoma samples is still to be performed and will be useful to stratify subtypes for prognostic outcome and for identifying new targets for generalized and personalized therapy. The goal of this project is two-fold: 1) To gain molecular insight into pediatric lymphoma by analysis of gene expression of single cells from lymphoma specimens and 2) To develop and use methods where specific alteration in gene expression can be examined functionally and for defining new personalized and generalized therapeutic approaches. We will obtain fresh lymphoma tissue and blood samples, FACS sort lymphocytes including lymphoma cells and run single cell RNA sequencing at ESCG at SciLifeLabs. Single cell RNA sequencing will be combined with histology analysis and functional assays established in our laboratory.