الفهرس 
Immune System and CancerOnly 14 pages are availabe for public view
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Abstract
Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder of a pluripotent stem cell characterized by excessive accumulation of myeloid cells in hematopoietic tissues with less than 20% blasts in peripheral blood and bone marrow.
CML is a disease most frequently occurring in the middle age with a peak in the 5th and 6th decades of life, affecting about 1-2 persons/ 100.000. CML shows a characteristic bi- or triphasic course, starting with an indolent chronic course lasting for 3-5 years. It eventually transforms into accelerated or blastic phases that resembles acute leukemia.
CML is characterized by the presence of a reciprocal translocation t (9; 22) (q34;q11) which generates abnormal fusion protein that exhibits constitutive tyrosine kinase activity and promote growth and survival of CML cells.
Tumor cells can suppress immunity by secreting immune inhibitory molecules. One of these molecules is programmed death receptor ligand 1 (PDL1), that acts as a co-inhibitory molecule for T cells by binding the programmed death receptor-1 (PD-1).
The high expression of PD-L1 in cancer patients leads to disease progression due to T cell exhaustion and suppression of T-
cell migration, proliferation, and secretion of cytotoxic mediators that restrict tumor cell killing.
Experimentally, there was a high expression of PDL1 on leukemic cells of a mouse model and that PDL1 blockade enhanced survival of CML mice in blast crisis. In addition, High expression of PDL1 has been implicated in resistance to cancer immunotherapy.
Across multiple cancer types, the inhibition of PDL1 by using the engineered humanized antibody against PDL1 is being most effective in patients in which preexisting immunity is suppressed by PDL1, and is reinvigorated on antibody treatment.
The aim of this study is to assess the plasma level of programmed cell death ligand 1 in patients with chronic myelogenous leukemia and its correlation with prognostic parameters and response to first line therapy.
This study was carried on 80 subjects. They were classified into two groups; group (I) included forty (40) patients were diagnosed with chronic phase chronic myeloid leukemia, and group (II) included forty (40) healthy subjects served as control group.
In group (I) the patients were subdivided into 3 subgroups; Subgroup (A): Newly diagnosed CML patients (n= 11) Subgroup (B): Imatinib responding CML patients (n=17) Subgroup (C): Imatinib resistant CML patients (n=12).
This study was carried out at the Hematology Department, College of
Medicine, Ain Shams University Hospitals.
CML patients (group I) were subjected to the following:
• Full clinical assessment
• Laboratory investigations:
o Complete blood count (CBC),
o Peripheral blood smear examination,
o Bone marrow aspiration
o Cytogenetic analysis for Philadelphia chromosome.
• Abdominal Ultrasound imaging.
• Assessment of plasma Programmed Cell Death Ligand 1(PDL-1), which was detected by enzyme-linked immune sorbent assay (ELISA) based on double antibody sandwich technology.
- There was highly significant increased plasma PDL-1 level in CML group and subgroups compared to the control group.
- Plasma PDL-1 levels of Imatinib resistant subgroup showed a significant decreased level versus newly diagnosed subgroup of CML patients.
- In CML group PDL-1 ranged between (1496 – 3997) ng/L with mean
± SD (2506.7± 649.8), while in control group, PDL-1 ranged between
(901 – 1159) ng/L with mean ± SD (1068.1 ± 80.3).
- In newly diagnosed CML subgroup, PDL-1 ranged between (1496 – 3997) ng/L with mean ± SD (2648.0±825.6), in Imatinib responding CML subgroup PDL-1 ranged between (1626 – 3594) ng/L with mean ± SD (2484.7±670.9), and in Imatinib resistant CML subgroup PDL-1 ranged between (2000 – 3539) ng/L with mean ± SD (2408.3± 437.5).
- There was a significant decrease in TLC in Imatinib responding CML
subgroup versus Imatinib resistant CML subgroup.
- Plasma PDL-1 levels showed a negative correlation with TLC in Imatinib resistant subgroup.
- Imatinib responding subgroup showed a significant decreased PCR ratio versus newly diagnosed subgroup and the Imatinib resistant subgroup showed a highly significant increased PCR ratio versus Imatinib responding subgroup.
- The suggested PDL-1 cut-off value for diagnosis of CML is 1327.5 ng/L, but the cut-off value between responsive and resistant CML subgroups cannot be detected, as there is no significant difference between both subgroups.
Conclusion:
The present work revealed an increased plasma PDL-1 level in chronic myelogenous leukemia patients, as a risk factor for CML incidence. In addition, each CML subgroup (newly diagnosed, Imatinib responding and Imatinib resistant subgroups) showed a highly significant increased PDL-1 level compared to the control group.
Imatinib resistant subgroup showed a significant decreased level of
PDL-1 versus newly diagnosed subgroup of CML patients.
Imatinib responding CML subgroup showed a significant decreased TLC versus Imatinib resistant CML subgroup, while the later showed a negative correlation with TLC.
Imatinib responding subgroup showed a significant decreased PCR ratio versus newly diagnosed subgroup, and the Imatinib resistant subgroup showed a highly significant increased PCR ratio versus Imatinib responding subgroup.
The suggested PDL-1 cut-off value for diagnosis of CML is 1327.5 ng/L.