Olga K. Weinberg, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USAFollow
Karen M. Chisholm, Department of Pathology, Seattle Children's Hospital, Seattle, WA, USA
Chi Young Ok, Departments of Hematopathology, M.D. Anderson Cancer Center, Houston, TX, USA
Yuri Fedoriw, Department of Pathology, University of North Carolina, Chapel Hill, NC, USA
Bartosz Grzywacz, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
Jason H. Kurzer, Department of Pathology, Stanford University Medical Center, Palo Alto, CA, USA
Emily F. Mason, Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
Karen A. Moser, Department of Pathology, University of Utah, Salt Lake City, UT, USA
Siddharth Bhattacharya, Department of Pathology and Laboratory Medicine, the University of Pennsylvania, Philadelphia, PA, USA
Mina Xu, Department of Pathology, Yale School of Medicine, New Haven, CT, USA
Daniel Babu, Department of Pathology, University of New Mexico, Albuquerque, NM, USA
Kathryn Foucar, Department of Pathology, University of New Mexico, Albuquerque, NM, USA
Wayne Tam, epartment of Pathology, Weill Cornell Medical College, New York, NY, USA
Adam Bagg, Department of Pathology and Laboratory Medicine, the University of Pennsylvania, Philadelphia, PA, USA
Attilio Orazi, Departments of Pathology, Texas Tech University Health Sciences Center, PL Foster School of Medicine, El Paso, TX, USA
Tracy I. George, Department of Pathology, University of Utah, Salt Lake City, UT, USA
Wei Wang, Departments of Hematopathology, M.D. Anderson Cancer Center, Houston, TX, USA
Sa A. Wang, Departments of Hematopathology, M.D. Anderson Cancer Center, Houston, TX, USA
Daniel A. Arber, Department of Pathology and Laboratory Medicine, University of Chicago, Chicago, IL, USA
Robert P. Hasserjian, Department of Pathology, Massachusetts General Hospital, Boston, MA, USA

Document Type

Article

Publication Date

7-1-2021

Abstract

Natural killer (NK) cells are lymphocytes of the native immune system that play a pivotal role in host defense and immune surveillance. While the conceptual view of NK-neoplasms is evolving, little is known about the rare NK lymphoblastic leukemia (NK-LL), which remains as a provisional entity in the 2016 WHO Classification. The goal of this study is to characterize NK-LL cases and compare with other CD56 co-expressing acute leukemias. We identified 105 cases, diagnosed as NK-LL (6), CD56+ acute undifferentiated leukemia (AUL) (6), CD56+ T-lymphoblastic leukemia (T-LL) (51), and CD56+ acute myeloid leukemia (AML) (42). Compared to AUL patients, NK-LL patients were significantly younger (p = 0.021) and presented with higher white blood cell (WBC) (p = 0.037) and platelet counts (p = 0.041). Flow cytometry showed more frequent expression of cytoplasmic CD3 (cCD3, p = 0.064) and CD33, (p = 0.065), while HLA-DR was significantly absent from NK-LL (p = 0.035) compared to AUL. Compared to T-ALL, NK-LL cases showed less frequent cCD3 (p = 0.002), CD4 (p = 0.051), and CD10 expression (p = 0.06). The frequency of abnormal karyotypes was similar between NK-LL, AUL, and T-ALL. The mutational profile differed in four leukemia groups, with a significance enrichment of NOTCH1 (p = 0.002), ETV6 (p = 0.002) and JAK3 (p = 0.02) mutations in NK-LL as compared to AML. As compared to T-ALL, NK-LL cases showed a higher number of total mutations (p = 0.04) and significantly more frequent ETV6 mutations (p = 0.004). Clinical outcome data showed differences in overall survival between all four groups (p = 0.0175), but no difference in event free survival (p = 0.246). In this largest study to date, we find that that NK-LL shows clinical presentation, immunophenotypic and molecular characteristics distinct from AUL, T-ALL, and AML. Our findings suggest NK-LL is a distinct acute leukemia entity and should be considered in the clinical diagnosis of acute leukemias of ambiguous lineage.

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