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Genetic and clinical distinction between aggressive NK-cell leukemia and extranodal NK/T-cell lymphoma with bone marrow involvement
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Genetic and clinical distinction between aggressive NK-cell leukemia and extranodal NK/T-cell lymphoma with bone marrow involvement
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Journal Article
Genetic and clinical distinction between aggressive NK-cell leukemia and extranodal NK/T-cell lymphoma with bone marrow involvement
2025
Overview
Aggressive NK-cell leukemia (ANKL) shares common clinicopathological features with extranodal NK/T-cell lymphoma with bone marrow (BM) involvement (ENKTL-BM), making their distinction challenging in BM examination. Despite numerous studies, genetic differences between the two diseases remained largely unclear. To investigate the genetic and clinical differences between ANKL and ENKTL-BM, we performed targeted sequencing of 282 genes and survival analyses on 15 ANKL and 5 ENKTL-BM patients. Mutation frequency of
FAT
family genes was higher in ANKL than in ENKTL-BM (80.0% vs. 0.0%,
P
= 0.004), and
FAT1
gene mutations were associated with significantly lower survival rates in ANKL patients (
P
= 0.002). Copy number alterations including 11q loss and 4q loss were detected exclusively in ANKL. The interval from symptom onset to death was significantly shorter (113.0 vs. 440.5 days,
P
= 0.027) and survival rate was significantly lower (
P
= 0.004) in ANKL than in ENKTL-BM. In conclusion, ANKL exhibited a higher mutation frequency of
FAT
family genes, a more acute fulminant clinical course, and worse prognosis than ENKTL-BM, indicating that ANKL and ENKTL-BM can be distinguished both genetically and clinically. We expect the identified
FAT1
gene mutations to serve as novel prognostic factors for ANKL.
Publisher
Nature Publishing Group UK,Nature Portfolio
Subject
/ Adult
/ Aged
/ Extranodal NK/T-cell lymphoma
/ FAT1
/ Female
/ Humanities and Social Sciences
/ Humans
/ Leukemia, Large Granular Lymphocytic - diagnosis
/ Leukemia, Large Granular Lymphocytic - genetics
/ Leukemia, Large Granular Lymphocytic - mortality
/ Leukemia, Large Granular Lymphocytic - pathology
/ Lymphoma, Extranodal NK-T-Cell - diagnosis
/ Lymphoma, Extranodal NK-T-Cell - genetics
/ Lymphoma, Extranodal NK-T-Cell - mortality
/ Lymphoma, Extranodal NK-T-Cell - pathology
/ Male
/ Mutation
/ Science
