Detection Of Peripheral Blood Lymphocyte Subsets In Chronic Myeloid Leukemia And Its Clinical Significance

Objective:Chronic myeloid leukemia?CML?is a malignant clonal disease of myeloid hematopoietic stem cells.Changes in immune function are closely related to the occurrence,development,and prognosis of the disease.Some of the patients who achieve remission on Tyrosine Kinase Inhibitor?TKI?therapy could partially achieve Treatment Free Remission?TFR?,and the peripheral blood lymphocyte subsets were associated with it.Lymphocytes are an important component of the immune system and are commonly used as indicators to monitor the immune status of patients.Current studies have found that the proportion and function of peripheral blood lymphocyte subsets have changed in newly diagnosed patients.TKI not only can reduce the tumor burden but also affect the peripheral blood lymphocyte subsets proportion and function,but the results of the current study are not consistent.The purpose of this study is to investigate the status of lymphocyte subsets in CML patients at diagnosis and on TKI therapy who achieved remission at different levels,and to clarify the correlation between tumor burden,TKI drugs and lymphocyte subsets in peripheral blood,and to provide a theoretical basis for predicting treatment response and prognosis.Methods:From October 2014 to March 2017,we collected 116 chronic phase CML patients who were all adults from the Cancer Center of the First Hospital of Jilin University.30 persons were collected from The Medical Examination Center in 2015 as health control group.Sex,age,clinical stage,risk stratification and other relevant clinical data were collected.Two milliliters of venous blood were obtained from outpatient.Real-time fluorescence quantitative polymerase chain reaction?qRT-PCR?was used to measure BCR-ABL quantification and flow cytometry?FCM?was used to detect lymphocyte subsets.The rank sum test was used to analyze the peripheral blood lymphocyte subsets in different stages of CML patients.Results:1.There was no statistical significance among healthy group,CML group,Pre-MMR group,MMR group,MR^4.5 group in the proportion of peripheral blood CD3⁺T,CD4⁺T,CD8⁺T lymphocyte proportion,CD4⁺/CD8⁺T lymphocyte ratio?P=0.251,P=0.078,P=0.088,P=0.060?.2.The proportion of peripheral blood NKT cells in the Pre-MMR group was higher than that in the healthy group,MMR group with lower BCR-ABL quantification?P=0.001,P=0.039?,and higher than that in the MR^4.5 group with higher BCR-ABL quantification?P=0.039?;The NKT cell proportion in the MR^4.5 group was higher than that in the healthy group?P=0.006?.3.The proportion of peripheral blood NK cells in the healthy group and MR⁴.5.5 group was higher than that in the CML group,Pre-MMR group,MMR group?P=0.006?P=0.007,P=0.007?P=0.021,P=0.005?P=0.022?.In Pre-MMR group,MMR group,MR^4.5 group,there was no statistical significance in the difference of proportion of peripheral blood NK cells with each other.In healthy group and MR^4.5 group,there was no statistically significant in the difference of proportion of peripheral blood NK cells between them.4.The proportion of peripheral blood Treg cells in MR^4.5 group was lower than that in healthy group,CML group,Pre-MM R group,and MMR group?P=0.000,P=0.001,P=0.045,P=0.002??5.In the Pre-MMR group,the proportion of peripheral blood NKT cells was higher in imatinib group than CML group?P=0.043?,and there was no significant difference in the proportion of other lymphocyte subsets.There was no significant difference in the proportion of peripheral blood lymphocyte subsets between nilotinib group and CML group.In the MMR group,there was no significant difference in peripheral blood lymphocyte subsets between CML group and imatinib group.The proportion of peripheral blood lymphocyte subsets in one patient treated with nilotinib was not significantly higher or lower than that of newly diagnosed CML patients.In the MR^4.5 group,imatinib had no effect on the proportion of peripheral blood CD3⁺T,CD4⁺T,CD8⁺T lymphocytes,ratio of CD4⁺/CD8⁺T lymphocytes,NKT cells.Imatinib reduced the proportion of peripheral blood Treg cells in CML patients who had achieved MR^4.5,and it was lower than the healthy level?P=0.005?.Imatinib increased the proportion of peripheral blood NK cells in CML patients who had achieved MR^4.5,it reached a healthy level?P=0.009?.Conclusions:1.The proportion of CD3⁺T,CD4⁺T,CD8⁺T lymphocytes and CD4⁺/CD8⁺T ratio in peripheral blood of newly diagnosed CML patients and CML patients on TKI therapy were not significantly different from those in healthy group.2.The correlation between the proportion of peripheral blood NKT cells and tumor burden in CML patients is not clear yet.3.The proportion of NK cells in the peripheral blood of newly diagnosed CML patients was lower than that of healthy people.With the deepening of remission,the proportion of NK cells increased,and it returned to a healthy level when CML patients achieve MR^4.5.4.The proportion of Treg cells in the peripheral blood of newly diagnosed CML patients was not significantly different from that of healthy people.With the deepening of remission,the proportion of Treg cells decreased,and it was lower than healthy level when CML patients achieve MR^4.5.5.TKI can not only reduce the tumor burden,but also increase the proportion of NK cells in peripheral blood of CML patients and reduce the proportion of Treg cells.TKI have no effect on the proportion of CD3⁺T,CD4⁺T,CD8⁺T lymphocytes,CD4⁺/CD8⁺T lymphocyte ratio and NKT cells.6.The relationship between peripheral blood lymphocyte subsets and different remission status,prognosis of CML patients needs to be further clarified.