Deregulated cellular apoptosis is a hallmark of cancer and chemotherapy resistance. The B-cell lymphoma 2 (BCL-2) protein family members are sentinel molecules that regulate the mitochondrial apoptosis machinery and arbitrate cell fate through a delicate balance between pro- and anti-apoptotic factors. The recognition of the anti-apoptotic BCL2 gene as an oncogenic driver in hematological malignancies has directed attention toward unraveling the biological significance of each of the BCL-2 superfamily members in cancer progression and garnered interest in the targeting of apoptosis in cancer therapy. Accordingly, the approval of venetoclax (ABT-199), a small molecule BCL-2 inhibitor, in patients with chronic lymphocytic leukemia and acute myeloid leukemia has become the proverbial torchbearer for novel candidate drug approaches selectively targeting the BCL-2 superfamily. Despite the inspiring advances in this field, much remains to be learned regarding the optimal therapeutic context for BCL-2 targeting. Functional assays, such as through BH3 profiling, may facilitate prediction of treatment response, development of drug resistance and shed light on rational combinations of BCL-2 inhibitors with other branches of cancer therapy. This review summarizes the pathological roles of the BCL-2 family members in cancer, discusses the current landscape of their targeting in clinical practice, and highlights the potential for future therapeutic inroads in this important area.
The prevalence of CLNM was 43.2%. In patients with N2 disease, the presence of CLNM was significantly associated with a poorer DSS, OS, and increased risk of distant metastasis recurrence.
Many challenges remain in diagnosing monoclonal immunoglobulin-associated renal disease, despite widespread application of immunofluorescence (IF) and immunohistochemistry. Here, we report a newly diagnosed case of multiple myeloma with clinical suspicion of renal amyloidosis, which had negative IF staining for kappa and lambda light chains in the glomeruli. Although laser microdissection and mass spectrometry-based proteomic analysis have emerged as important tools for amyloid typing in the literature, such facilities are still not widely available in Asia. We propose that a clinicopathological algorithm for the evaluation of organized monoclonal renal deposits, together with a combined nephrological-haematological approach, will still be adequate to generate an unequivocal diagnosis in the majority of cases.
Background
Early identification of patients at risk of severe dengue disease (DD) is critical to guide its management. We evaluated whether the atypical lymphocyte count (ALC), generated from the Sysmex automated full blood count analyzer, is predictive of severe thrombocytopenia secondary to Dengue infection.
Methods
We prospectively collected data on patients admitted with DD between December 2017 and October 2018. ALC data were extracted from the Sysmex XS500i analyzer from day 1 to day 7 of admission. Clinical data were obtained from patients' medical records.
Results
We enrolled 256 patients with DD. A negative correlation between ALC on admission and platelet count on day 5 to day 7 (Spearmen's correlation; day 5:-0.485, day 6:-0.428 and day 7:-0.344) (p=0.001) was observed. Based on receiver operator characteristic curve analysis, we found that an ALC of >0.5x103/L had 90% sensitivity and 70% specificity for severe thrombocytopenia (platelet count <50x109/L) on day 5. The positive and negative predictive values were 74.4 and 91.2%, respectively (power 84.7).
Conclusions
We propose that ALC on admission may be a novel negative predictive factor for severe thrombocytopenia on day 5 to day 7 of DD. Further studies are required to validate our findings and evaluate whether ALC is predictive of other complications of DD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.