Immune cell proportions correlate with clinicogenomic features and ex vivo drug responses in acute myeloid leukemia

IntroductionThe implementation of small-molecule and immunotherapies in acute myeloid leukemia (AML) has been challenging due to genetic and epigenetic variability amongst patients. There are many potential mechanisms by which immune cells could influence small-molecule or immunotherapy responses, yet, this area remains understudied.MethodsHere we performed cell type enrichment analysis from over 560 AML patient bone marrow and peripheral blood samples from the Beat AML dataset to describe the functional immune landscape of AML.ResultsWe identify multiple cell types that significantly correlate with AML clinical and genetic features, and we also observe significant correlations of immune cell proportions with ex vivo small-molecule and immunotherapy responses. Additionally, we generated a signature of terminally exhausted T cells (Tex) and identified AML with high monocytic proportions as strongly correlating with increased proportions of these immunosuppressive T cells.DiscussionOur work, which is accessible through a new “Cell Type” module in our visualization platform (Vizome; http://vizome.org/), can be leveraged to investigate potential contributions of different immune cells on many facets of the biology of AML

Ground-based near-UV observations of 15 transiting exoplanets: constraints on their atmospheres and no evidence for asymmetrical transits

Transits of exoplanets observed in the near-UV have been used to study the scattering properties of their atmospheres and possible star-planet interactions. We observed the primary transits of 15 exoplanets (CoRoT-1b, GJ436b, HAT-P-1b, HAT-P-13b, HAT-P-16b, HAT-P-22b, TrES-2b, TrES-4b, WASP-1b, WASP-12b, WASP-33b, WASP-36b, WASP-44b, WASP-48b, and WASP-77Ab) in the near-UV and several optical photometric bands to update their planetary parameters, ephemerides, search for a wavelength dependence in their transit depths to constrain their atmospheres, and determine if asymmetries are visible in their light curves. Here, we present the first ground-based near-UV light curves for 12 of the targets (CoRoT-1b, GJ436b, HAT-P-1b, HAT-P-13b, HAT-P-22b, TrES-2b, TrES-4b, WASP-1b, WASP-33b, WASP-36b, WASP-48b, and WASP-77Ab). We find that none of the near-UV transits exhibit any non-spherical asymmetries, this result is consistent with recent theoretical predictions by Ben-Jaffel et al. and Turner et al. The multiwavelength photometry indicates a constant transit depth from near-UV to optical wavelengths in 10 targets (suggestive of clouds), and a varying transit depth with wavelength in 5 targets (hinting at Rayleigh or aerosol scattering in their atmospheres). We also present the first detection of a smaller near-UV transit depth than that measured in the optical in WASP-1b and a possible opacity source that can cause such radius variations is currently unknown. WASP-36b also exhibits a smaller near-UV transit depth at 2.6 sigma. Further observations are encouraged to confirm the transit depth variations seen in this study.NASA's Planetary Atmospheres programme; Virginia Space Grant Consortium Graduate Research Fellowship Program; National Science Foundation [DGE-1315231]; University of Arizona Astronomy Club; Steward Observatory TAC; Lunar and Planetary LaboratoryThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Integrative analysis of drug response and clinical outcome in acute myeloid leukemia

Acute myeloid leukemia (AML) is a cancer of myeloid-lineage cells with limited therapeutic options. We previously combined ex vivo drug sensitivity with genomic, transcriptomic, and clinical annotations for a large cohort of AML patients, which facilitated discovery of functional genomic correlates. Here, we present a dataset that has been harmonized with our initial report to yield a cumulative cohort of 805 patients (942 specimens). We show strong cross-cohort concordance and identify features of drug response. Further, deconvoluting transcriptomic data shows that drug sensitivity is governed broadly by AML cell differentiation state, sometimes conditionally affecting other correlates of response. Finally, modeling of clinical outcome reveals a single gene, PEAR1, to be among the strongest predictors of patient survival, especially for young patients. Collectively, this report expands a large functional genomic resource, offers avenues for mechanistic exploration and drug development, and reveals tools for predicting outcome in AML. [Display omitted] •Acute myeloid leukemia patient cohort with clinical, molecular, drug response data•Validation and discovery of diverse biological features of drug response•Broad mapping of tumor cell differentiation state affecting response to drugs•Modeling reveals a strong and targetable determinant of clinical outcome Bottomly et al. present a functional genomic resource composed of molecular, clinical, and drug response data on acute myeloid leukemia patient specimens. Through integration of all of these data, they identify genetic and cell differentiation state features that predict drug response, and they utilize modeling to identify targetable determinants of clinical outcome