Lymphoid subsets in acute myeloid leukemias: Increased number of cells with NK phenotype and normal T-cell distribution

Abstract

Natural killer (NK) and T subsets were analyzed with appropriate dual labeling by flow cytometry in peripheral blood (PB) (66 cases) and bone marrow (BM) (55 cases) from patients with de novo AML in order to determine: (a) their distribution at diagnosis, (b) the correlation between PB and BM in NK subpopulations, (c) their relationship with the clinical and hematological disease characteristics, and (d) the changes occurring upon achieving complete remission (CR). NK cells defined by the expression of CD56 in the absence of CD3 were significantly increased at diagnosis and their levels in PB correlated with those of BM. By contrast, NK subsets defined by CD16 expression (CD16+ CD2+ and CD16+ CD2- NK-cell subsets) as well as T lymphocytes with NK activity (CD56+ CD3+), although increased in PB, displayed normal levels in BM. An additional observation of interest was the expansion of an immature NK population lacking CD16 Ag expression (CD56+ CD16-). AML cases were divided into two groups according to the absolute number of NK cells in PB; patients with the highest levels showed an increased proportion of blast cells in PB (p = 0.01), monocytic subtypes (p = 0.03), and expression of CD11b, CD14, and CD4 antigens (p = 0.05). Infections at diagnosis were not related to the level of NK cells. In 19 patients who achieved complete remission the number of CD56+ CD3- cells tended to be reduced to within the normal range. Other T-cell populations, including the CD4 naive and memory cells, were also explored, their distribution being normal in the PB of AML patients. By contrast, the cytotoxic subset CD8+/CD57+ was significantly increased (p < 0.001). These data point to the existence of marked alterations of NK cells in AML patients, possibly reflecting a host-tumor immunological interaction.

Peripheral blood T cells in acute myeloid leukemia (AML) patients at diagnosis have abnormal phenotype and genotype and form defective immune synapses with AML blasts

“…on May 12, 2018. by guest www.bloodjournal.org From being decreased as is generally perceived or normal as reported in 2 previous studies, 17,18 were in fact increased, with particular amplification of CD8 cells. An increase in CD3 ϩ CD56 ϩ T cells was seen in the PB but not BM of AML patients and these showed an effector phenotype.…”

“…Only 2 previous studies have addressed the issue of absolute T-cell numbers in the PB at the time of diagnosis with AML. 17,18 We report here our findings characterizing T cells in PB of newly diagnosed AML patients compared with age-matched healthy controls. Surprisingly, we report that the absolute number of PB T cells in AML patients is increased, as are CD3 ϩ 56 ϩ cells.…”

Antibodies targeting human IL1RAP (IL1R3) show therapeutic effects in xenograft models of acute myeloid leukemia

“…NK cells are considered the most important effector cell type in humans (30,33,34). The feasibility of an antibody-based immunotherapy depending on NK cells in AML is supported by reports showing that NK cell numbers are intact in AML patients (35) and that the levels of CD16, which activates NK cells for ADCC (36), is equal in AML patients and healthy subjects (37). Collectively, these data show that the effect of anti-IL1RAP immunotherapy in the MA9Ras xenograft model is mediated by effector cells and suggests that effector-cell-mediated mechanisms is an important and accessible mode of action in a future clinical setting.…”

The Immunological Dilemma: Cellular Innate and Adaptive Immune Response Versus Human Acute Myeloid Leukemia

“…+ CD2 + and CD16 + CD2 -NK cells were then found significantly increased in peripheral blood, but only the CD56 + NK cells were additionally increased in bone marrow [4]. When these authors divided the AML cases into two groups according to the absolute number of circulating NK cells, the patients with the highest levels also showed an increased proportion of circulating leukemic blasts [4].…”

“…Elevated levels of lymphocytes with NK phenotype have been reported at the *Address correspondence to this author at the Elisabeth Ersvaer, Section for Haematology, Institute of Medicine, University of Bergen, N-5021 Bergen, Norway; Tel: +47 55 97 30 76; Fax: +47 55 97 29 50; E-mail: elisabeth.ersvar@med.uib.no time of diagnosis in AML [4]. CD56 + , CD16…”