Acute myeloid leukemia (AML) is a bone marrow malignancy characterized by clonal expansion and differentiation arrest of bone marrow progenitor cells. Previous exposure to therapeutic, occupational, or environmental DNA damaging agents is a predisposing factor, but most AML cases remain without a clear etiology. AML is the most common acute leukemia in adults, and its survival is short, with a 5-year survival rate of only 24%. Intensive chemotherapy and gene stem cell transplantation are usually suitable for a small number of young patients, and for most elderly people, their prognosis and survival rate are poor. Therefore, it is necessary to further explore the molecular mechanism of AML in order to find effective drugs for the treatment of AML as soon as possible. CD BioSciences provides precise in vivo transfection services to assist in the study of the molecular functions of acute myelogenous leukemia-related genes.

Figure 1. Blood cell development. (From cancer.gov)

Target Genes Delivered In Vivo in Acute Myelogenous Leukemia

Through years of continuous development and research of molecular biology techniques, FLT3, Bcl-2, IDH1/2 and other mutant genes have been discovered in acute myelogenous leukemia.

FLT3

FLT3 belongs to the type III receptor tyrosine kinase family and is a membrane-bound receptor expressed in hematopoietic cells with an intrinsic tyrosine kinase domain. FLT3 binds ligand to activate the tyrosine kinase domain, promotes the phosphorylation of various sites within the domain, and finally activates AMP kinase, STAT, and AKT/PI3 kinase signal transduction pathways, thereby affecting cell differentiation, proliferation, and apoptosis. The internal tandem duplication of the proximal membrane region (FLT3-ITD) found in this gene is the most common mutation, with a positive rate of about 23%-25% in AML patients, and is associated with leukocytosis and high relapse rate, eventually leading to Overall survival rate decreased.

Bcl-2

The BCL family promotes cell survival by sequestering and binding pro-apoptotic proteins in cells, including BCL-2, BCL-XL, MCL1, etc.. BCL-2 is highly expressed in leukemia stem cells in AML and is associated with low CR rate and shortened survival time.

IDH1/2

IDH1/2 are metabolic enzymes that catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate in the tricarboxylic acid cycle, and are located in the cytoplasm and mitochondria respectively. IDH2 mutant enzymes can catalyze the reduction of α-HG to the competing metabolite R-2-hydroxyglutarate (R-2-HG), leading to abnormal DNA hypermethylation and differentiation arrest in myeloid precursors, ultimately promoting the occurrence of leukemia. IDH1 mutation occurs in about 6%-16% of AML patients, and IDH2 mutation rate is about 8%-19%.

In addition, some studies have obtained more related genes through bioinformatics technology, namely NFKB1, PSMB8, NFKBIA, PSMC3, PSMD4, PSMD7, PSMD2, PSMC4, PSME2 and PSME3. Among them, PSMB8, NFKB1, NFKBIA, PSMC3, and PSMC4 are involved in the occurrence, angiogenesis, and metastasis of AML, and have been widely studied in AML; while PSMD2, PSMD4, PSMD7, PSME2, and PSME3 have not been studied in AML.

In addition to the above genes, there are interesting acute myelogenous leukemia-related genes that need to be explored and studied. Therefore, there is a need for an in vivo transfection system that can precisely target acute myelogenous leukemia tissue and be taken up by tumor cells to function in vivo. The system can help researchers overcome various challenges encountered during in vivo transfection:

• Relevant molecular function studies can only be carried out in vitro, lacking important in vivo data
• Using in vitro transfection system for in vivo transfection, the transfection efficiency is very low;
• The in vivo transfection system used is not specific to Acute myelogenous leukemia tissues and cells, and is toxic to the body;
• The in vivo transfection system used cannot penetrate the Acute myelogenous leukemia tissue into the tumor tissue;
• The nucleic acid load of the in vivo transfection system is low, and it is difficult to achieve the expected effect;
• Etc…

Our Advantage:

• We can provide an in vivo transfection system for Acute myelogenous leukemia tissues and cells to achieve efficient transfection
• Our system can target multiple targets at the same time, improving targeting accuracy
• The in vivo transfection system has low toxicity to the body and is safe to use
• In vivo transfection system vectors can protect nucleic acids from degradation during in vivo delivery
• Persistent knockout effect in experimental animals after a single injection
• The system load is high, and the transfection needs of different doses can be completed
• Professional design and service team to provide you with reliable service and technical support
• Timely feedback of technical reports

CD BioSciences specializes in developing transfection systems and customizing transfection reagents for gene transfection using our core technologies. With our high-quality products and services, your transfection results can be greatly improved. If you can't find a perfect in vivo transfection system, you can contact us. We can provide one-to-one personal customization service.

References

1. ALLEMANI C, et al.; Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. The Lancet. 2018, 391(10125): 1023- 1075.
2. Levis M. Midostaurin approved for FLT3-mutated AML. Blood. 2017, 129: 3403-3406.
3. Tsao T, et al.; Concomitant inhibi-tion of DNA methyltransferase and BCL-2 proteinfunction synergistically induce mitochondrial apopto-sis in acute myelogenous leukemia cells. Ann He-matol. 2012, 91:1861-1870.
4. Ward PS, et al.; The common feature of leukemia -associated IDHl and IDH2 mutations is aneomorphic enzyme activity converting-ketoglutarateto 2-hydroxyglutarate. Cancer Cell. 2010, 17:225-234.

* For research use only. Not for use in clinical diagnosis or treatment of humans or animals.