The role of adjuvant chemotherapy in the management of acute promyelocytic leukemia differentiation syndrome.

Acute Promyelocytic Leukemia (APL) is characterized by the t(15;17) chromosomal translocation resulting in a PML-RARA fusion protein. The all-trans-retinoic acid (ATRA) and Arsenic Trioxide (ATO) only regimens have demonstrated success in treating low- and intermediate-risk patients. However, induction with ATRA/ATO only regimens have been showing increased incidence of differentiation syndrome (DS), a potentially lethal complication, traditionally treated with dexamethasone. We conducted a three-institution retrospective study, aiming to evaluate the role of short-term adjuvant chemotherapy in managing moderate DS for patients with low- or intermediate-risk APL initially treated with ATRA/ATO only protocols. We evaluated the difference in incidence and duration of moderate DS in APL patients who were treated with ATRA/ATO with or without adjuvant chemotherapy. 57 low- or intermediate-risk APL patients were retrospectively identified and included for this study; 36 patients received ATRA/ATO only induction treatment, and 21 patients received ATRA/ATO/adjuvant chemotherapy combination induction therapy. Similar proportions of patients experienced DS in both groups (66.7% vs. 81.0%, P = 0.246). The median duration of DS resolution in patients receiving ATRA/ATO only was 17 days (n = 23), and in patients receiving combination therapy was 8 days (n = 16) (P = 0.0001). The lengths of hospital stay in patients receiving ATRO/ATO only was 38 days (n = 7), and in patients receiving combination therapy was 14 days (n = 17) (P = 0.0007). In conclusion, adding adjuvant chemotherapy to ATRA/ATO only protocol may reduce the duration of DS and the length of hospital stay during APL induction treatment

Accounting for diverse evolutionary forces reveals mosaic patterns of selection on human preterm birth loci

There is a need for analytical frameworks to investigate the evolution of complex genetic traits. Here, the authors develop an approach to simultaneously evaluate different evolutionary signatures on trait-associated genetic variants for complex traits and apply it to study spontaneous preterm birth

An alternative splicing switch in FLNB promotes the mesenchymal cell state in human breast cancer.

Alternative splicing of mRNA precursors represents a key gene expression regulatory step and permits the generation of distinct protein products with diverse functions. In a genome-scale expression screen for inducers of the epithelial-to-mesenchymal transition (EMT), we found a striking enrichment of RNA-binding proteins. We validated that QKI and RBFOX1 were necessary and sufficient to induce an intermediate mesenchymal cell state and increased tumorigenicity. Using RNA-seq and eCLIP analysis, we found that QKI and RBFOX1 coordinately regulated the splicing and function of the actin-binding protein FLNB, which plays a causal role in the regulation of EMT. Specifically, the skipping of FLNB exon 30 induced EMT by releasing the FOXC1 transcription factor. Moreover, skipping of FLNB exon 30 is strongly associated with EMT gene signatures in basal-like breast cancer patient samples. These observations identify a specific dysregulation of splicing, which regulates tumor cell plasticity and is frequently observed in human cancer

Supplementary Table S1 from Oncogenic KRAS Drives Lipofibrogenesis to Promote Angiogenesis and Colon Cancer Progression

Supplementary Table S1 includes differentially expressed genes from 4 fibroblast subtypes</p

Supplementary Figure S1 from Oncogenic KRAS Drives Lipofibrogenesis to Promote Angiogenesis and Colon Cancer Progression

Figure S1 demonstrates the enrichment of lipid-rich CAFs within the stroma of Kras*-driven CRC.</p

Supplementary Table S4 from Oncogenic KRAS Drives Lipofibrogenesis to Promote Angiogenesis and Colon Cancer Progression

Supplementary Table S4 shows primers used for RT-qPCR and ChIP-qPCR</p