Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by reduced differentiation of myeloid cells and uncontrolled cell proliferation. AML is prone to drug resistance and has a high recurrence rate during treatment with cytarabine-based chemotherapy. Our study aims to explore the cell differentiation effect of a potent histone deacetylase inhibitor (HDACi), I13, and its possible mechanism on AML cell lines (Kasumi-1, KG-1, MOLM-13 and NB4). It has been shown that I13 can significantly inhibit proliferation and colony formation of these AML cells by inducing cell differentiation coupled with cell-cycle exit at G0/G1. Mechanically, I13 presented the property of HDAC inhibition, as assessed by the acetylation of histone H3, which led to the differentiation of Kasumi-1 cells. In addition, the HDAC inhibition of I13 likely dictated the activation of the antigen processing and presentation pathway, which maybe has the potential to promote immune cells to recognize leukemic cells and respond directly against leukemic cells. These results indicated that I13 could induce differentiation of M3 and M5 subtypes of AML cells, M2 subtype AML cells with t(8;21) translocation and leukemic stem-like cells. Therefore, I13 could be an alternative compound which is able to overcome differentiation blocks in AML.
Acute leukemia (AL) is characterized by excessive proliferation and impaired differentiation of leukemic cells. AL includes acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Previous studies have demonstrated that about 10% of AML and 22% of ALL are mixed lineage leukemia gene rearrangements (MLLr) leukemia. The prognosis of MLLr leukemia is poor and new therapeutics are urgently needed. Differentiation therapy with all-trans-retinoic acid (ATRA) has prolonged the 5-years disease-free survival rate in acute promyelocytic leukemia (APL), a subtype of AML. However, the differentiation therapy has not been effective in other acute leukemia. Here, we aim to explore the cell differentiation effect of the potent HDACs inhibitor, I1, and the possible mechanism on the MLLr-AML and MLLr-ALL cells (MOLM-13, THP-1, MV4-11 and SEM). It is shown that I1 can significantly inhibit the proliferation and the colony-forming ability of MOLM-13, THP-1, MV4-11 and SEM cells by promoting cell differentiation coupled with cell cycle block at G0/G1 phase. We show that the anti-proliferative effect of I1 attributed to cell differentiation is most likely associated with the HDAC inhibition activity, as assessed by the acetylation of histone H3 and H4, which may dictates the activation of hematopoietic cell lineage pathway in both MOLM-13 and THP-1 cell lines. Moreover, the activity of HDAC inhibition of I1 is stronger than that of SAHA in MOLM-13 and THP-1 cells. Our findings suggest that I1, as a chromatin-remodeling agent, could be a potent epigenetic drug to overcome differentiation block in MLLr-AL patients and would be promising for the treatment of AL.
In this study, a rapid detection method using picric acid test strip for detection of sodium cyanide in ocean water was established, and an automatic-integrated detection device was set up, which can be mounted on an unmanned surface vehicle. The optimal detection conditions were set as follows: for a 100-ml seawater sample, the weight of tartaric acid solid was 1.5 g, 1–2 drops of 150 g/L sodium carbonate were used to soak the picric acid test strip, the heating temperature was 80 °C, and the heating time was 5 min. Under the optimal conditions, the test result was satisfactory and the detection limit of the method achieved was 0.3 mg/L. This method realizes the remote and rapid detection of sodium cyanide in seawater, which greatly improves the detection efficiency and does not require any personnel to enter the contaminated site. It can be widely used for rapid detection scenarios such as leakage accidents from overseas transportation, lake pollution emergencies and on-site screening.
Acute myeloid leukemia (AML) is a clinical and genetic heterogeneous disease with a poor prognosis. Recent advances in genomics and molecular biology have immensely improved the understanding of disease. The advantages of syndrome differentiation and treatment are strong selectivity, good curative effect and lesser side effects. In recent years, according to the molecular mechanism of acute myeloid leukemia, many new therapeutic targets have been found. New targets of differentiation therapy in recent years, such as cell cyclin-dependent kinase (CDK2), isocitrate dehydrogenase (IDH1, IDH2), Homeobox genes (HoxA9), Dihy-droorotate dehydrogenase (DHODH) and some others, are reviewed in this article.
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