Aggressive NK Cell Leukemia: Current State of the Art.
Siba El HusseinL Jeffrey MedeirosJoseph D KhouryPublished in: Cancers (2020)
Aggressive natural killer (NK) cell leukemia (ANKL) is a rare disease with a grave prognosis. Patients commonly present acutely with fever, constitutional symptoms, hepatosplenomegaly, and often disseminated intravascular coagulation or hemophagocytic syndrome. This acute clinical presentation and the variable pathologic and immunophenotypic features of ANKL overlap with other diagnostic entities, making it challenging to establish a timely and accurate diagnosis of ANKL. Since its original recognition in 1986, substantial progress in understanding this disease using traditional pathologic approaches has improved diagnostic accuracy. This progress, in turn, has facilitated the performance of recent high-throughput studies that have yielded insights into pathogenesis. Molecular abnormalities that occur in ANKL can be divided into three major groups: JAK/STAT pathway activation, epigenetic dysregulation, and impairment of TP53 and DNA repair. These high-throughput data also have provided potential therapeutic targets that promise to improve therapy and outcomes for patients with ANKL. In this review, we provide a historical context of the conception and evolution of ANKL as a disease entity, we highlight advances in diagnostic criteria to recognize this disease, and we review recent understanding of pathogenesis as well as biomarker discoveries that are providing groundwork for innovative therapies.
Keyphrases
- radiation therapy
- nk cells
- high throughput
- dna repair
- dna damage
- gene expression
- acute myeloid leukemia
- neoadjuvant chemotherapy
- dna methylation
- big data
- intensive care unit
- liver failure
- type diabetes
- high resolution
- machine learning
- single cell
- prognostic factors
- mesenchymal stem cells
- stem cells
- drug induced
- adipose tissue
- newly diagnosed
- physical activity
- electronic health record
- climate change
- data analysis
- deep learning
- case report
- sensitive detection
- human health
- cell therapy
- patient reported outcomes
- patient reported