The Effect and Mechanism of Novel Telomerase Inhibitor Nilo 22 on Leukemia Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the cytotoxic effect and its mechanism of the micromolecule compound on the leukemia cells.@*METHODS@#The cytotoxic effects of 28 Nilotinib derivatives on K562, KA, KG, HA and 32D cell lines were detected by MTT assays, and the compound Nilo 22 was screen out. Cell apoptosis and cell cycle on leukemia cells were detected by flow cytometry. The effect of compound screened out on leukemogenesis potential of MLL-AF9 leukemia mice GFP@*RESULTS@#Nilo 22 serves as the most outstanding candidate out of 28 Nilotinib derivatives, which impairs leukemia cell lines, but spares normal hematopoietic cell line. Comparing with Nilotinib, Nilo 22 could induce the apoptosis of GFP@*CONCLUSION@#Nilo 22 shows a significant cytotoxic effect on mice and human leukemia cells, especially for drug resistance cells. Nilo 22 is a promising anti-leukemia agent to solve the common clinical problems of drug resistance and relapse of leukemia.

Literature Analysis of the Selection of Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia Patients with BCR-ABL35INS Mutation / 中国药房

OBJECTIVE： To provide reference for reasonable selection of tyrosine kinase inhibitors （TKI） in chronic myeloid leukemia （CML） patients with BCR-ABL35INS mutation. METHODS： Using “BCR-ABL insertional mutation” “ABL1 35ins mutation” “BCR-ABL c.1423_1424ins35” “ABL1 p.C475Tyrfs*11” as keywords， retrieved from CNKI， Wanfang database， Medline and COSMIC database， BCR-ABL35INS mutation CML patients were summarized and analyzed in respects of general information and treatment （treatment plan， patient compliance and drug withdrawal）， therapeutic effect （molecular biological mitigation and disease progress） and safety data （ADR） during 2007-2018. RESULTS： Totally 9 related literatures were included， involving 70 patients with BCR-ABL35INS mutation， all of them were foreign cases. Among them， 39 cases were male and 31 cases were female， with a median age of 49.2 years. The median time from the diagnosis of CML to the detection of BCR-ABL35INS mutation was 19 months. After detecting gene mutation， 39 cases were treated with imatinib （initial dose of 400 mg， po， once a day）， and molecular biological remission was achieved in 5 patients （12.9％）； 15 cases （38.5％） had molecular biological response but had disease progression； 8 patients （20.5％） had no response. Seventeen patients were treated with dasatinib （100 mg， po， once a day or 2 divided dose）， and 8 cases （47.1％） achieved molecular biological response. Twenty-one patients were treated with nilotinib （400 mg， po， 2 divided dose）， and 3 patients （14.3％） achieved molecular biological response； 2 patients achieved molecular biological response， but the disease progressed. Seven， three and seven of these patients stopped taking drugs due to adverse reactions， accounting for 17.9％， 17.6％ and 33.3％ respectively. All the ADRs were classified as grade 3-4 of the National Cancer Institute’s Common Terminology Criteria for Adverse Events， and most of them were hematological toxicity. CONCLUSIONS： CML patients with BCR-ABL35INS mutation are less likely to achieve molecular response on imatinib therapy but are more sensitive to dashatinib. In the course of treatment， we should strengthen the monitoring of blood system and other related indicators to ensure the safety and effectiveness of drug use.

ADAR1 Knockout Inhibits Notch1-induced T-ALL in Mice / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of ADAR1 on the occurrence and development of mouse T cell acute lymphoblastic leukemia (T-ALL).</p><p><b>METHODS</b>Lck-Cre; ADAR1lox/lox mice were generated through interbreeding. The lineage-cells of Lck-Cre; ADAR1lox/lox mice and the control were enriched respectively by the means of MACS, and the lin- cells were transfected with retrovirus carrying MSCV-ICN1-IRES-GFP fusion gene. Then the transfection efficiency was detected by the means of FACS, and the same number of GFP+ cells were transplanted into lethally irradiated recipient mice to observe the survival of mice in 2 recipient group after transplantation.</p><p><b>RESULTS</b>T cell-specific knockout ADAR1 mice were generated, and Notch1-induced T-ALL mouse model was established successfully. The leukemia with T-ALL characteristics occured in the mice of control group, but did not in the ADAR1 kmockout mice after transplantation.</p><p><b>CONCLUSIONS</b>ADAR1 plays a key role in the incidence and development of Notch1-induced T-ALL.</p>