Nowadays, PTCL diagnosis requires the integration of information about clinical status, morphology, immunohistochemistry, flow cytometry, cytogenetics and molecular biology. On the other hand, T-cell acute lymphoblastic leukemia (T-ALL), a T-cell neoplasm of lymphoblasts, accounts for about 15% and 25% of acute lymphoblastic leukemia (ALL) cases in pediatric and adult cohorts, respectively. Among these, PTCL-NOS is the most widespread subtype worldwide and typically represents a variant that does not meet the criteria for other subtypes. T-cell lymphomas (TCLs) are the most common group, and within this subgroup the major subtypes are peripheral TCL (PTCL), not otherwise specified (PTCL-NOS), angioimmunoblastic T cell lymphoma (AITL), anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) and ALK-negative ALCL. The most recent WHO Classification established 23 subtypes grouped by clinical presentation. T and NK-cell leukemia/lymphoma is a collection of aggressive disorders with unfavorable outcome accounting for 10–15% of non-Hodgkin lymphomas. The combined integration of mutational/expression changes forms a useful tool with which new compounds may be assayed. Integrated mutational and immunohistochemical analysis shows that mutational changes cannot fully explain the activation of key survival pathways and the resulting phenotypes. This panel of cell lines captures the complexity of T/NK-cell lymphoproliferative processes samples, with the partial exception of AITL cases. Immunohistochemical analysis showed nuclear accumulation of MYC (in 85% of the cases), NFKB (62%), p-STAT (44%) and p-MAPK (30%). We also found common alterations in JAK/STAT and epigenetic pathways. The study identified TP53, NOTCH1 and DNMT3A as the most frequently mutated genes. To this end, targeted sequencing was performed alongside the expression of specific biomarkers corresponding to potentially activated survival pathways. To gain deeper insights into the deregulated mechanisms promoting this disease, we searched a panel of 31 representative T-cell and 2 NK-cell lymphoma/leukemia cell lines for predictive markers of response to targeted therapy. T and NK-cell lymphoma is a collection of aggressive disorders with unfavorable outcome, in which targeted treatments are still at a preliminary phase.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |