Mature T- and NK-Cell Neoplasms

Abstract

With a few exceptions, mature T- and NK-cell leukemias/lymphomas are aggressive neoplasms. They tend to be challenging to diagnose due to their uncommon occurrences, the overlapping features among various entities, and perhaps the imperfect sensitivity and specificity of T-cell receptor gene rearrangement as a reliable indicator of T-cell malignancy. The rapid advancements in molecular diagnostic techniques in recent years, such as whole genome/exome sequencing, array comparative genomic hybridization, microRNA, and microarray gene expression profiling, have shed light on the molecular pathogenesis of many of the lymphoma entities. In some situations, a better understanding of the molecular profile of a lymphoma has led to its reclassification. One example relates to reclassification of the previously recognized nodal peripheral T-cell lymphoma (PTCL) with T follicular helper features now under the same diagnostic category as angioimmunoblastic T-cell lymphoma that is known to share T follicular helper features. Certain molecular events can profoundly influence the prognosis of patients given the same diagnostic entity, as in the case of ALK-negative anaplastic large cell lymphoma harboring DUSP22 or TP63 gene rearrangements. Contemporary molecular genetic techniques have also contributed to our understanding of JAK-STAT activation in cytotoxic T-cell neoplasms, such as T-cell large granular lymphocyte leukemia. In fact, gain-of-function STAT3 mutations along the JAK-STAT cascade may represent a common pathogenic link among various natural killer cell (NK-cell) neoplasms. The knowledge derived from molecular genetic advancements in T-/NK-cell neoplasms holds promise in paving the way for the development of novel therapeutic targets that can eventually lead to better clinical outcomes.