Abstract
T-prolymphocytic leukemia is a rare and aggressive hematological malignancy characterized by the clonal proliferation of mature lymphoid T-cells. The pathogenesis of T-PLL is closely linked to specific chromosomal abnormalities, primarily involving the proto-oncogene T-cell leukemia/lymphoma 1 gene family. Recent advancements in molecular profiling have identified additional genomic aberrations, including those affecting the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway. This case report presents a patient with T-prolymphocytic leukemia whose cytogenetic and molecular analysis revealed a t(X;14)(q28;q11.2) translocation and a STAT5B mutation. Here, we aim to review the genetic and molecular underpinnings of T-prolymphocytic leukemia, as well as current treatment options, with a focus on the anti-CD52 monoclonal antibody alemtuzumab and JAK inhibitors. While alemtuzumab followed by allogeneic hematopoietic stem cell transplantation remains the standard of care for eligible patients, its efficacy is limited and many patients are ineligible. Emerging therapeutic approaches, such as JAK/STAT inhibitors, offer promising potential for improving patient outcomes.