Search

Anaplastic large cell lymphoma (ALCL) is a mature T cell neoplasm that often expresses the [CD4.sup.+] T cell surface marker. It usually harbors the t(2;5) (p23;q35) translocation, leading to the ectopic expression of NPM-ALK, a chimeric tyrosine kinase. We demonstrated that in vitro transduction of normal human [CD4.sup.+] T lymphocytes with NPM-ALK results in their immortalization and malignant transformation. The tumor cells displayed morphological and immunophenotypical characteristics of primary patient-derived anaplastic large cell lymphomas. Cell growth, proliferation, and survival were strictly dependent on NPM-ALK activity and include activation of the key factors STAT3 and DNMT1 and expression of CD30 (the hallmark of anaplastic large-cell lymphoma). Implantation of NPM-ALK-transformed [CD4.sup.+] T lymphocytes into immunodeficient mice resulted in the formation of tumors indistinguishable from patients' anaplastic large cell lymphomas. Integration of 'Omic' data revealed that NPM-ALK-transformed [CD4.sup.+] T lymphocytes and primary [NPM-ALK.sup.+] ALCL biopsies share similarities with early T cell precursors. Of note, these [NPM-ALK.sup.+] lymphoma cells overexpress stem cell regulators (OCT4, SOX2, and NANOG) and HIF2A, which is known to affect hematopoietic precursor differentiation and [NPM-ALK.sup.+] cell growth. Altogether, for the first time our findings suggest that NPM-ALK could restore progenitor-like features in mature [CD30.sup.+] peripheral [CD4.sup.+] T cells, in keeping with a thymic progenitor-like pattern., Introduction Systemic anaplastic large cell lymphomas (ALCLs) account for 2% to 8% of non-Hodgkin's lymphomas in adults and approximately 10% to 30% of lymphomas in children. The majority (80%) of [...]