Clinical Characteristics of Aggressive NK-Cell Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore and summarize the clinical characteristics and treatment of aggressive NK-cell leukemia (ANKL), and provide new insights for clinical diagnosis and treatment of this disease.@*METHODS@#The clinical data of 7 patients with ANKL admitted to the First Affiliated Hospital of Wannan Medical College from March 2014 to July 2021 were retrospectively analyzed, and their clinical characteristics, laboratory and imaging results, treatment and outcomes were analyzed.@*RESULTS@#Among the 7 patients, 5 were males and 2 were females, with a median age of 47 (33-69) years old. The morphology of bone marrow cells in 7 patients showed similar large granular lymphocytes. Immunophenotyping revealed abnormal NK cells in 5 cases. By the end of follow-up, 6 cases died and 1 case survived, with a median survival time of 76.9 (4-347) days.@*CONCLUSION@#ANKL is a rare disease with short course and poor prognosis. If combined with hemophagocytic syndrome (HPS), the prognosis is even worse. There is no unified treatment method at present, and the use of PD-1 inhibitors may prolong the survival in some patients.

Allogeneic hematopoietic stem cell transplantation for children with aggressive natural killer cell leukemia: one case report with a literature review / 中华器官移植杂志

Objective:To summarize the clinical features, treatments and prognoses of aggressive natural killer cell leukemia (ANKL) in children.Methods:Clinical data and follow-up results were retrospectively reviewed for one hospitalized case of ANKL in June 2019.Through a literature search, the relevant items were retrieved from the databases of China National Knowledge Infrastructure, WanFang and PubMed using the Chinese and English keywords of "aggressive natural killer cell leukemia" and "children" up to December 2021.Results:This 8-year-old girl was diagnosed with ANKL by flow cytometric immunophenotype and immunohistochemical stain.Fever was the initial manifestation accompanied by sallow complexion, fatigue, enlargement of liver, spleen and lymph node and hematopenia of three lines.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed after chemotherapy.As of April 2022, the child stayed in a disease-free survival state after follow-ups for over 2 years.The literature search finally yielded 7 eligible Chinese and 10 English reports with a total of 17 pediatric ANKLs.In this group, there were fever (n=15), rash (n=1), perineal mass (n=1) and diarrhea, vomiting and other digestive tract symptoms (n=1). Six cases were misdiagnosed during an early stage of disease.4 cases received chemotherapy alone, 3 cases received chemotherapy regimen for acute lymphoblastic leukemia, 1 child died and one death occurred after received chemotherapy regimen of "cisplatin + vincristine + doxorubicin + ifosfamide". Allo-HSCT was performed in 5 patients after remission with chemotherapy and one child died from multiple organ failure at 9 months after allo-HSCT.Nine cases gave up treatment.Conclusions:ANKL has a rapid disease progression, diverse clinical manifestations, easy misdiagnosis and poor prognosis.For suspected ANKL cases, clinicians perform multiple bone perforations at multiple sites and immunophenotype by flow cytometry as soon as possible to confirm the diagnosis.Currently allo-HSCT offers a long-term survival of ANKL patients.

Usefulness of Chromosomal Microarray in Hematologic Malignancies: A Case of Aggressive NK-cell Leukemia with 1q Abnormality

A variety of clonal cytogenetic abnormalities have been reported in aggressive natural killer (NK)-cell lymphoma and leukemia. Recent chromosomal microarray studies have shown both gain and loss of 1q and loss of 7p as recurrent abnormalities in aggressive NK-cell leukemia. Here, we report a case of aggressive NK-cell leukemia with complex chromosomal gains and losses, as confirmed by chromosomal microarray analysis. The patient showed an aggressive clinical course, which was complicated by hemophagocytic lymphohistiocytosis. Conventional cytogenetic analysis revealed trisomy 3 and 1q gain only. However, chromosomal microarray analysis detected an additional gain of 1q21.1–q24.2 and a loss of 1q24.2–q31.3. These abnormal lesions might play a role in the pathogenesis of aggressive NK-cell leukemia by inactivating tumor suppressor genes or by activating oncogenes. These results suggest that chromosomal microarray analysis may be used to provide further genetic information for patients with hematological malignancies, including aggressive NK-cell leukemia.

Generation of a Genetically Engineered Aggressive Nk-Cell Leukemia Cell Line with Stable IL2 Expression.

Introduction: Aggressive NK-cell leukemia (ANKL) is a highly aggressive disease with extremely poor prognosis. A few malignant NK cell lines reflecting ANKL biology have been generated; however, these NK cell lines require the inclusion of exogeneous IL2 in the culture medium continuously, which increases the cost of cell culture significantly. Methods: IL2 coding sequenced was cloned into MSCV-IRES-YFP (PMIY) vector by directional PCR-cloning. IL2 was ectopically expressed in KHYG1 cell line through retroviral transduction. The transduced cells were cultured in limiting IL2 concentrations during which they were quantified with flow cytometry in regular time intervals to track the transduced population. IL2 transduced KHYG1 cells were then sorted to generate IL2-KHYG1 cells. PRDM1 was ectopically expressed in IL2-KHYG1 cells through retroviral transduction. Trypan blue count was performed to test proliferation of IL2-KYHG1 cells in the absence of IL2. Results: IL2-KHYG1 cells were enriched (from ~7% to ~16% YFP+ cells) during cell culture in limiting (6.25IU) IL2 concentrations. Complete removal of IL2 further enriched the transduced portion to 27% YFP-positivity, which did not increase with additional culturing. IL2 expressing KHYG1 cells were further enriched by sorting transduced IL2-KHYG1 cells with high level IL2 expression. IL2-KHYG1 cells survived and continued to grow without IL2. IL2-KHYG1 cells were transduced successfully using a PRDM1 construct having GFP as a marker under cell culture conditions having no IL2. Conclusion: IL2-KHYG1 cell line may decrease the cost associated with culturing ANKL cell lines, and it may facilitate in vitro investigation of the molecular basis of this malignancy.