Chronic myelomonocytic leukemia (CMML) is a rare and challenging type of myeloproliferative neoplasm. Poor prognosis and high mortality, associated predominantly with progression to secondary acute myeloid leukemia (sAML), is still an unsolved problem. Despite a growing body of knowledge about the molecular repertoire of this disease, at present, the prognostic significance of CMML-associated mutations is controversial. The absence of available CMML cell lines and the small number of patients with CMML make pre-clinical testing and clinical trials complicated. Currently, specific therapy for CMML has not been approved; most of the currently available therapeutic approaches are based on myelodysplastic syndrome (MDS) and other myeloproliferative neoplasm (MNP) studies. In this regard, the development of the robust CMML animal models is currently the focus of interest. This review describes important studies concerning animal models of CMML, examples of methodological approaches, and the obtained hematologic phenotypes.
NK-cells as innate immunity elements manifest key reactions of antitumor immune response. NKG2D is an activating transmembrane receptor of NK-cells which is responsible for cytotoxicity initiation in response to the binding of specific ligands of genetically modified cells. Selective expression of NKG2D ligands provides a unique perspective on the therapy of wide variety of tumors. Acute myeloid leukemias (AML) are malignant hematological tumors with a high relapse risk. Due to the complexity of AML treatment strategy it is necessary to develop new approaches to tumor elimination using novel genetic constructs. Currently available CAR T-cell drugs with NKG2D receptor are successfully subjected to clinical studies in AML patients and prove their high therapeutic potential.
Background. FLT3 gene is an important prognostic molecular marker in acute myeloid leukemia (AML). However, the detection of FLT3 mutations presents a challenge. Aim. To compare techniques used for the detection of FLT3 mutations, and to develop a test-system based on polymerase chain reaction (PCR) for quick and reliable determination of FLT3 mutation status. Materials & Methods. Bone marrow samples obtained from AML patients were subjected to examination. To detect FLT3-ITD and FLT3-TKD mutations PCR was performed with subsequent agarose gel electrophoresis visualization. The results were verified by Sanger sequencing. The data obtained using our test-system were compared with widely applied commercial kit ‘FLT3 Mutation Assay for Gel Detection’ by Invivoscribe. Results. To determine the FLT3 mutation status a PCR test was developed. This technique was validated on 22 bone marrow samples obtained from AML patients. FLT3-ITD mutation was detected in 4 patients, 3 patients showed FLT3-TKD mutation. In 1 patient both mutations were identified. These results fully corresponded to the molecular genetic analysis of FLT3, performed by ‘FLT3 Mutation Assay for Gel Detection’. The chosen technique was validated using Sanger sequencing data analysis. Conclusion. The article offers the review of all existing FLT3 mutation screening techniques and describes the experience of developing the PCR test for FLT3-ITD and FLT3-TKD mutation detection. The chosen technique is affordable and easy to use compared with the others. This study can be used as a guide for both doctors and researchers.
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