Journal Article

Clinical, immunophenotypic and genomic findings of NK lymphoblastic leukemia: a study from the Bone Marrow Pathology Group

Weinberg, Olga K., Bhattacharya, Siddharth, Babu, Daniel, Wang, Wei, Hasserjian, Robert P., Moser, Karen A., Mason, Emily F., Fedoriw, Yuri, Kurzer, Jason H., Bagg, Adam, Wang, Sa A., Foucar, Kathryn, Grzywacz, Bartosz, Orazi, Attilio, Arber, Daniel A., Chisholm, Karen M., George, Tracy I., Xu, Mina, Tam, Wayne, Ok, Chi Young

2021

Overview

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.

• Publisher: Elsevier Inc,Nature Publishing Group US,Elsevier Limited
• Subject: 13/31 / 45/23 / 631/67/68 / 692/308/575 / Acute lymphoblastic leukemia / Acute myeloid leukemia / Adolescent / Aged / Bone marrow / CD3 antigen / CD4 antigen / CD56 antigen / CD56 Antigen - analysis / Child / Child, Preschool / Female / Flow cytometry / Histocompatibility antigen HLA / Humans / Immune system / Immunophenotyping / Immunosurveillance / Karyotypes / Killer Cells, Natural - pathology / Laboratory Medicine / Leukemia / Lymphatic leukemia / Lymphocytes / Lymphocytes T / Male / Medicine / Medicine & Public Health / Mutation / Myeloid leukemia / Natural killer cells / Notch1 protein / Pathology / Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics / Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality / Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology / Retrospective Studies