METHODS: We used a combination of proliferation and apoptosis assays to assess the effect of JB on AML cell lines and patient samples, with BH3 profiling being performed to identify early effects of the drug (4 h). Phosphokinase arrays were adopted to identify potential driver proteins in the cellular response to JB, the results of which were confirmed and extended using western blotting and inhibitor assays and measuring levels of reactive oxygen species.
RESULTS: AML cell growth was significantly impaired following JB exposure in a dose-dependent manner; potent colony inhibition of primary patient cells was also observed. An apoptotic mode of death was demonstrated using Annexin V and upregulation of apoptotic biomarkers (active caspase 3 and cleaved PARP). Using BH3 profiling, JB was shown to prime cells to apoptosis at an early time point (4 h) and phospho-kinase arrays demonstrated this to be associated with a strong upregulation and activation of both total and phosphorylated c-Jun (S63). The mechanism of c-Jun activation was probed and significant induction of reactive oxygen species (ROS) was demonstrated which resulted in an increase in the DNA damage response marker γH2AX. This was further verified by the loss of JB-induced C-Jun activation and maintenance of cell viability when using the ROS scavenger N-acetyl-L-cysteine (NAC).
CONCLUSIONS: This work provides the first evidence of cytotoxicity of JB against AML cells and identifies ROS-induced c-Jun activation as the major mechanism of action.
MEHTODS: We studied 18 cases of haematological malignancies which comprised five patients with T-ALL, 12 patients with AML and one with biphenotypic leukaemia.
RESULTS: We found that the incidence of IGH gene rearrangement in T-ALL and AML were three (60%) and two (16.7%), respectively. The patient with biphenotypic leukaemia was negative for IGH gene rearrangement.
CONCLUSION: Immunoglobulin gene rearrangement, which occurs in almost all haematological malignancies of B-cell lineage, also presents in a very small proportion of T-cell or myeloid malignancies.
METHODS: This cross-sectional study analysed secondary data obtained from the health clinics in Sabah, Malaysia from January to August 2016. The Pearson Chi-square test was used to analyse the relationships between malaria infection and socio-demographic characteristics. Multivariable logistic regression was performed in order to determine the risk factors for malaria in Sabah.
RESULTS: Out of 1222 patients, 410 (33.6%) had a laboratory-confirmed malaria infection. Infection by Plasmodium knowlesi accounted for the majority of malaria reports in Sabah (n=340, 82.9%). Multivariable analysis indicated that males (prevalence odds ratio 0.023, 95% confidence interval 0.012-0.047) and those living in a rural area (prevalence odds ratio 0.004, 95% confidence interval 0.002-0.009) were at higher risk 24.0-95.9) and those living in a rural area (adjusted odds ratio 212.6, 95% confidence interval 105.8-427.2) were at higher risk of acquiring a malaria infection.
CONCLUSIONS: Malaria infections in Sabah, Malaysia are common, with P. knowlesi being the most common malaria parasite. The infection was associated with several socio-demographic and geographical factors. Thus, mitigation measures should be considered to address modifiable risk factors for malaria infection.