Abstract
The antitumor activity of NK cells in patients with chronic myeloid leukemia (CML) is inhibited by the leukemia microenvironment. Recent studies have identified that the expression of TIGIT, CD57, and KLRG1 is related to the function, maturation, and antitumor capabilities of NK cells. However, the characteristics of the expression of these genes in the peripheral blood (PB) and bone marrow (BM) from patients with CML remain unknown. In this study, we used multicolor flow cytometry to assay the quantity and phenotypic changes of NK cells in PB and BM from de novo CML (DN-CML) and CML patients acquiring molecular response (MR-CML). We found that the expression of TIGIT, which inhibits NK cell function, is increased on CD56+ and CD56dim NK cells in DN-CML PB compared with those in healthy individuals (HIs), and it is restored to normal in patients who achieve MR. We also found that the expression of CD57 on NK cells was approximately the same level in PB and BM from DN-CML patients, while decreased CD57 expression was found on CD56+ and CD56dim NK cells in HI BM compared with PB. Additionally, those two subsets were significantly increased in DN-CML BM compared to HI BM. The expression of CD57 correlates with replicative senescence and maturity for human NK cells; therefore, the increase in TIGIT on PB NK cells together with an increase in CD57 on BM NK cells may explain the subdued NK cell antileukemia capacity and proliferative ability in DN-CML patients. These results indicate that reversing the immune suppression of PB NK cells by blocking TIGIT while improving the proliferation of BM NK cells via targeting CD57 may be more effective in removing tumor cells.
Highlights
Chronic myeloid leukemia (CML) is characterized by the expression of the BCR/ABL1 fusion gene and the presence of the Philadelphia chromosome (Ph)
The results demonstrated that the CD57 expression level on the bone marrow (BM) and peripheral blood (PB) NK cell subsets from de novo CML (DN-CML) patients was approximately the same level (Figure 2(b))
We first described an increased level of TIGIT in PB NK cell subsets in DN-CML patients
Summary
Chronic myeloid leukemia (CML) is characterized by the expression of the BCR/ABL1 fusion gene and the presence of the Philadelphia chromosome (Ph) The product of this fusion gene is a protein with deregulated tyrosine kinase activity, resulting in a malignant clonal disorder of the hematopoietic stem cells in the bone marrow (BM) and the accumulation of immature myeloid cells in peripheral blood (PB) [1]. HIs: healthy individuals; CML: chronic myeloid leukemia; MR: molecular response; PB: peripheral blood; BM: bone marrow; IS: international standard; TKI: tyrosine kinase inhibitor. CML patients who have achieved a major molecular response (MMR, BCR/ABL ≤ 0:1%) or molecular response4.5 (MR4.5, BCR/ABL ≤ 0:0032%) show a larger proportion of mature, cytolytic CD57+CD62L− NK cells in PB with repertoires of activating and inhibitory receptors on NK cells restored to expression levels found in HIs [8].
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