Overexpression of Semaphorin-3A and Semaphorin-4D in the Peripheral Blood from Newly Diagnosed Patients with Chronic Lymphocytic Leukemia

Abstract

Background: Semaphorins play prominent roles in physiological and pathological processes such as vascular development, tumor growth and immune responses. Semaphorins have different roles in various kinds of cancers, but there is no study concerning their expression in the chronic lymphocytic leukemia (CLL). This study aimed to assess the SEMA3A, SEMA4A and SEMA4D expression in patients with CLL. 
 Materials and Methods: Peripheral blood specimens were collected from 30 newly-diagnosed untreated patients with CLL and 30 healthy subjects as a control group. The SEMA3A, SEMA4A and SEMA4D expression was determined by real-time PCR method. 
 Results: The fold change expression of SEMA3A and SEMA4D was 7.58 ± 2.66 and 3.20 ± 0.99 in patients with CLL, and was 1.01 ± 0.31 and 1.00 ± 0.27 in healthy subjects, respectively. The CLL patients expressed higher amounts of SEMA3A and SEMA4D in comparison with healthy subjects (P<0.02 and P<0.03, respectively). The fold change expression of SEMA3A in patients with stage II (11.12 ± 5.35) was also higher than patients with stage I (4.49 ± 1.61, P<0.05). No significant difference was also observed in the expression of SEMA4A and SEMA4D between patients with stage I and stage II CLL. In both CLL and control groups, the fold change expression of SEMA3A was higher in men than in women (P<0.03 and P<0.02, respectively).
 Conclusion: The results of the study indicated elevated expression of the SEMA3A and SEMA4D in patients with CLL. The SEMA3A expression was influenced by tumor stage and gender of participants.

Whole Transcriptome Analysis Revealed a Stress Response to Deep Underground Environment Conditions in Chinese Hamster V79 Lung Fibroblast Cells

“…Human concentrative nucleoside transporter-1 (hCNT1, SLC28A1) ( Wang and Buolamwini, 2019 ), Ccl20 ( Qiu et al, 2011 ), Sema4d ( Bhutia et al, 2011 ), and Arhgap36 ( Rack et al, 2014 ) have been shown to influence cellular growth and proliferation, and were the top down-regulated mRNAs in V79 cells cultured in a DUGL. Nuclear receptor 4A3 (NR4A3) has been shown to have the ability to suppress cell growth ( Zhang B. et al, 2018 ; Parsa et al, 2019 ). Importantly, NR4A3 was significantly up-regulated in cells cultured in a DUGL.…”

Class IV semaphorins in disease pathogenesis

“…Sema4D is associated with the etiology of various types of cancer 88,89 . Roles for Sema4D have been demonstrated in breast cancer, 90–101 colorectal carcer, 102–108 gastric cancer, 109 esophageal cancer, 110,111 lung cancer, 112–114 pancreatic cancer, 107,115–117 cholangiocarcinoma, 118 prostatic cancer, 119–123 bladder cancer, 124,125 kidney cancer, 125 cervical cancer, 126 ovarian cancer, 127–130 malignant melanoma, 131 osteosarcoma, 132 head‐and‐neck cancer, 133–137 medulloblastoma, 138 leukemia, 139–143 malignant lymphoma, 144 and multiple myeloma (Figure 4). 145 Cancer cells express Sema4D or its receptor, which are typically up‐ or down‐regulated in tumors compared to normal tissues.…”

Soluble Sema4D Level Is Positively Correlated with Sema4D Expression in PBMCs and Peripheral Blast Number in Acute Leukemia

“…Due to its important role in inflammation, Sema4D is also involved in cancer progression. It is highly expressed in breast cancer [ 13 ], pancreatic cancer [ 14 ], bladder cancer [ 15 ], head and neck squamous cell carcinoma [ 16 ], colon cancer [ 17 ], oral squamous cell carcinoma [ 18 ], ovarian cancer [ 19 ], gastric carcinoma [ 20 ], T cell non-Hodgkin's lymphomas [ 21 ], and chronic lymphoblastic leukemia [ 22 , 23 ]. Sema4D promotes the proliferation and metastasis of cancer cells [ 15 , 18 , 24 , 25 ].…”