KIT overexpression

This upregulation of target gene expression activated signalling pathways such as mTOR-AKT, ultimately resulting in malignant proliferation of bone marrow cells. In conclusion, this study offers insights into potential early targets for benzene-induced haematologic malignant diseases and provides novel perspectives for more targeted preventive and therapeutic strategies.

Bufalin differentially inhibited PDO growth and proliferation, induced apoptosis, restored E-cadherin, and downregulated CSC markers CD133 and C-Myc, dependent on C-Kit/Slug. These findings suggest that the C-Kit/Slug axis plays a pivotal role in regulating CRC stemness, and reveal that targeting this axis can inhibit CRC growth and progression.

C-KIT, TET1, and TET2 could be used as possible useful biomarkers for the diagnosis of AML.

Combination treatment with 4C9-DM1 plus carboplatin/etoposide or lurbinectedin resulted in a TGI rate greater than 90% compared with the vehicle control. Taken together, these results indicate that 4C9-DM1 is a potential therapeutic agent for SCLC treatment.

This linker-payload system is the same used in ado-trastuzumab emtansine, an approved ADC for HER2-positive breast cancer. There were no significant toxicities detected at doses up to 60 mg/kg in normal mice, suggesting a therapeutic index greater than 20 times. In conclusion, NN3201 showed potent anti-tumor activity and was selected as preclinical candidate.

Mantle cell lymphoma (MCL) is a neoplasm of mature lymphocytes committed to the B-cell lineage. This neoplasm has an aggressive clinical course, with poor response to standard treatment and short overall survival. MCL typical immunophenotype has been described as a mature monoclonal B-cell population with expression of CD19, CD20, CD43, CD45, CD79 and CD5; and negative expression of CD10, CD23 and CD200. Overexpression of cyclin D1 as detected by immunohistochemistry is characteristic of this disease. CD117 or c-kit is a surface protein encoded by the proto-oncogene c-kit which is expressed in normal hematopoietic and neoplastic cells, usually of myeloid lineage. There are few published studies with assessment of CD117 expression on mature B-cell neoplasms (MBCN). In this report, we described a MCL case with aberrant CD117 coexpression as demonstrated by flow cytometry immunophenotyping (FCI). Patient was a 64 year-old male with leukocytosis (39.20 x 109/l) and lymphopenia with normal red blood cell and platelet counts. Peripheral blood FCI with a screening panel evidenced an abnormal population representing 64% of nucleated cells, with expression of CD19, CD45(bright) and CD117. Additional staining of myeloid and lymphoid markers was performed. The neoplastic cells had positive expression of cytCD79a, CD5, CD19, CD20(bright), CD27, CD38, CD45(bright), CD43, CD79b, CD81, HLA-DR and kappa light chain; and were negative for cytCD3, cytMPO, CD10, CD11c, CD23, CD25, CD33, CD34, CD103, CD200 and lambda light chain. CD117 PE (clone 104D2, EXBIO, Praha, CZE) staining was repeated and positive expression was confirmed. FCI findings were compatible with the diagnosis of MCL with aberrant CD117 coexpression. After initial chemotherapy, patient had persistent leukocytosis (19.10 x 109/l) with anemia (hemoglobin of 11.1 g/l). Bone marrow aspirate FCI showed persistence of 37% of neoplastic cells. Unfortunately, patient died from causes unrelated to the disease before the next chemotherapy cycle. CD117 expression is a common finding in acute myeloid leukemia, being less frequently expressed in precursor lymphoid neoplasms and rarely identified in mature neoplasms. There are few studies evaluating CD117 expression in MBCN since its assessment is not part of the diagnostic panels. Assessment of c-kit mRNA expression in different types of lymphomas only identified its expression in CD30-positive cases. A CD117-positive B-cell non-Hodgkin lymphoma (NHL) carrying the t(14;18) translocation has been described in a case report. In another study, CD117 overexpression was identified in 2 out of 17 MCL cases using immunohistochemistry. Also, CD117 expression was identified in four out of 30 diffuse large B-cell lymphoma (DLBCL) cases. There is one large study assessing the distribution and expression of KIT in 824 cases of malignant lymphoma where CD117 expression was assessed with tissue microarray, and only one B-cell follicular lymphoma had positive CD117 expression. The role of CD117 expression on MBCN is still unclear, however, the abnormal expression of this marker has the potential to be used for FCI minimal residual disease (MRD) assessment. In Conclusion , CD117 expression can be found in MCBN such as MCL and expansion of FCI panel in order to better characterize such abnormal populations is necessary for the correct diagnosis.

In the multivariate model, overexpression of HER2 rather than c-KIT protein significantly predicted increased progression. Recurrence and progression of non-muscle-invasive bladder cancer correlate with overexpression of HER2 and c-KIT proteins in tumor cells.

Various studies have explored on c-kit and hepatocellular carcinoma, nevertheless, the intricate roles of c-kit in the liver are largely understudied. Herein, we extensively summarize previous studies geared toward providing hints for future clinical and basic research.

Cutaneous metastases were found to express CD117 at a level comparable to their primary tumors, suggesting that other mechanisms interfere directly with the metastatic process and not loss of c-Kit expression by itself. CD117 overexpression in cutaneous melanocytic lesions correlates significantly with increased immunostaining intensity, suggesting that the immunohistochemical evaluation of CD117 may be a good method for screening patients, who could benefit from personalized therapy with tyrosine kinase inhibitors.

Targeted therapies against these receptors such as IMATINIB and then SUNITINIB have transformed the management and prognosis of advanced and metastatic forms. Legal entity responsible for the study The author. Funding Has not received any funding.