As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer. Within chronic lymphocytic leukemia (CLL), responses to 62% of drugs were associated with 2 or more mutations, and linked the B cell receptor (BCR) pathway to trisomy 12, an important driver of CLL. Based on drug responses, the disease could be organized into phenotypic subgroups characterized by exploitable dependencies on BCR, mTOR, or MEK signaling and associated with mutations, gene expression, and DNA methylation. Fourteen percent of CLLs were driven by mTOR signaling in a non–BCR-dependent manner. Multivariate modeling revealed immunoglobulin heavy chain variable gene (IGHV) mutation status and trisomy 12 as the most important modulators of response to kinase inhibitors in CLL. Ex vivo drug responses were associated with outcome. This study overcomes the perception that most mutations do not influence drug response of cancer, and points to an updated approach to understanding tumor biology, with implications for biomarker discovery and cancer care.

Postdeposition solvent annealing of water-dispersible conducting polymers induces dramatic structural rearrangement and improves electrical conductivities by more than two orders of magnitude. We attain electrical conductivities in excess of 50 S∕cm when polyaniline films are exposed to dichloroacetic acid. Subjecting commercially available poly(ethylene dioxythiophene) to the same treatment yields a conductivity as high as 250 S∕cm. This process has enabled the wide incorporation of conducting polymers in organic electronics; conducting polymers that are not typically processable can now be deposited from solution and their conductivities subsequently enhanced to practical levels via a simple and straightforward solvent annealing process. The treated conducting polymers are thus promising alternatives for metals as source and drain electrodes in organic thin-film transistors as well as for transparent metal oxide conductors as anodes in organic solar cells and light-emitting diodes.electrical conductivity | solar cells | thin-film transistors | light-emitting diodes | polyaniline

We report the synthesis and characterization of a series of polyanilines (PANI) that are templated with a polymer acid at varying molecular weights. The polymer acid template of choice, poly(2-acrylamido-2-methyl-1-propanesulfonic acid), or PAAMPSA, was synthesized via conventional free-radical polymerization with molecular weights ranging from 45 kg mol 21 to 724 kg mol 21 . Subsequent aniline polymerization in the presence of PAAMPSA yielded waterdispersible, conductive PANI-PAAMPSA. The electrical conductivity of PANI-PAAMPSA increases by approximately three-fold with decreasing PAAMPSA molecular weight. This trend is accompanied by significant structural changes, including increases in PANI crystallinity and conjugation length. These conductivities (0.4-1.1 S cm 21 ) exceed the highest reported for polymer acid-doped PANI systems.

Mutations of the tumor suppressor p53 lead to chemotherapy resistance and a dismal prognosis in chronic lymphocytic leukemia (CLL). Whereas p53 targets are used to identify patient subgroups with impaired p53 function, a comprehensive assessment of non-coding RNA targets of p53 in CLL is missing. We exploited the impaired transcriptional activity of mutant p53 to map out p53 targets in CLL by small RNA sequencing. We describe the landscape of p53-dependent microRNA/non-coding RNA induced in response to DNA damage in CLL. Besides the key p53 target miR-34a, we identify a set of p53-dependent microRNAs (miRNAs; miR-182-5p, miR-7-5p and miR-320c/d). In addition to miRNAs, the long non-coding RNAs (lncRNAs) nuclear enriched abundant transcript 1 (NEAT1) and long intergenic non-coding RNA p21 (lincRNA-p21) are induced in response to DNA damage in the presence of functional p53 but not in CLL with p53 mutation. Induction of NEAT1 and lincRNA-p21 are closely correlated to the induction of cell death after DNA damage. We used isogenic lymphoma cell line models to prove p53 dependence of NEAT1 and lincRNA-p21. The current work describes the p53-dependent miRNome and identifies lncRNAs NEAT1 and lincRNA-p21 as novel elements of the p53-dependent DNA damage response machinery in CLL and lymphoma.