TY - JOUR
T1 - Aggressive nk cell leukemia
T2 - Current state of the art
AU - El Hussein, Siba
AU - Medeiros, L. Jeffrey
AU - Khoury, Joseph D.
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/10
Y1 - 2020/10
N2 - 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.
AB - 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.
KW - Biomarker
KW - Immunohistochemistry
KW - Leukemia
KW - Molecular
KW - NK cell
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U2 - 10.3390/cancers12102900
DO - 10.3390/cancers12102900
M3 - Review article
C2 - 33050313
AN - SCOPUS:85092250790
SN - 2072-6694
VL - 12
SP - 1
EP - 16
JO - Cancers
JF - Cancers
IS - 10
M1 - 2900
ER -