Meningioma transcriptomic landscape demonstrates novel subtypes with regional associated biology and patient outcome.

Meningiomas, although mostly benign, can be recurrent and fatal. World Health Organization (WHO) grading of the tumor does not always identify high-risk meningioma, and better characterizations of their aggressive biology are needed. To approach this problem, we combined 13 bulk RNA sequencing (RNA-seq) datasets to create a dimension-reduced reference landscape of 1,298 meningiomas. The clinical and genomic metadata effectively correlated with landscape regions, which led to the identification of meningioma subtypes with specific biological signatures. The time to recurrence also correlated with the map location. Further, we developed an algorithm that maps new patients onto this landscape, where the nearest neighbors predict outcome. This study highlights the utility of combining bulk transcriptomic datasets to visualize the complexity of tumor populations. Further, we provide an interactive tool for understanding the disease and predicting patient outcomes. This resource is accessible via the online tool Oncoscape, where the scientific community can explore the meningioma landscape.

Population genomic and biophysical modeling show different patterns of population connectivity in the spiny lobster Jasus frontalis inhabiting oceanic islands.

Knowledge about connectivity between populations is essential for the fisheries management of commercial species. The lobster Jasus frontalis inhabits two oceanic island groups, the Juan Fernández Archipelago and the Desventuradas Islands, separated by 800 km. Since this species is primarily exploited in the Juan Fernández Archipelago, knowledge of the connectivity patterns among islands is foundational for species management. Here, we used variability at single-nucleotide polymorphisms (SNPs) and individual-based modeling (IBM) to estimate the genetic structure and connectivity between J. frontalis populations in these island groups. The variability at 9090 SNPs suggests two genetic populations, one in the Juan Fernández Archipelago and one in the Desventuradas Islands. Furthermore, IBM suggests an asymmetric connectivity pattern, with particles moving from the Juan Fernández Archipelago to the Desventuradas Islands but not vice versa. Since the IBM analysis suggests asymmetric larval movement between the islands, and the genetic analysis indicates isolation between the Juan Fernández Archipelago and the Desventuradas Islands, larval retention mechanisms such as small-scale oceanographic processes or behavior could hinder larval movement between islands. This study highlights the importance of using more than one methodology to estimate population connectivity.

YEASTRACT+: a portal for the exploitation of global transcription regulation and metabolic model data in yeast biotechnology and pathogenesis.

YEASTRACT+ (http://yeastract-plus.org/) is a tool for the analysis, prediction and modelling of transcription regulatory data at the gene and genomic levels in yeasts. It incorporates three integrated databases: YEASTRACT (http://yeastract-plus.org/yeastract/), PathoYeastract (http://yeastract-plus.org/pathoyeastract/) and NCYeastract (http://yeastract-plus.org/ncyeastract/), focused on Saccharomyces cerevisiae, pathogenic yeasts of the Candida genus, and non-conventional yeasts of biotechnological relevance. In this release, YEASTRACT+ offers upgraded information on transcription regulation for the ten previously incorporated yeast species, while extending the database to another pathogenic yeast, Candida auris. Since the last release of YEASTRACT+ (January 2020), a fourth database has been integrated. CommunityYeastract (http://yeastract-plus.org/community/) offers a platform for the creation, use, and future update of YEASTRACT-like databases for any yeast of the users' choice. CommunityYeastract currently provides information for two Saccharomyces boulardii strains, Rhodotorula toruloides NP11 oleaginous yeast, and Schizosaccharomyces pombe 972h-. In addition, YEASTRACT+ portal currently gathers 304 547 documented regulatory associations between transcription factors (TF) and target genes and 480 DNA binding sites, considering 2771 TFs from 11 yeast species. A new set of tools, currently implemented for S. cerevisiae and C. albicans, is further offered, combining regulatory information with genome-scale metabolic models to provide predictions on the most promising transcription factors to be exploited in cell factory optimisation or to be used as novel drug targets. The expansion of these new tools to the remaining YEASTRACT+ species is ongoing.

Mechanical feedback defines organizing centers to drive digit emergence.

During embryonic development, digits gradually emerge in a periodic pattern. Although genetic evidence indicates that digit formation results from a self-organizing process, the underlying mechanisms are still unclear. Here, we find that convergent-extension tissue flows driven by active stresses underlie digit formation. These active stresses simultaneously shape cartilage condensations and lead to the emergence of a compressive stress region that promotes high activin/p-SMAD/SOX9 expression, thereby defining digit-organizing centers via a mechanical feedback. In Wnt5a mutants, such mechanical feedback is disrupted due to the loss of active stresses, organizing centers do not emerge, and digit formation is precluded. Thus, digit emergence does not result solely from molecular interactions, as was previously thought, but requires a mechanical feedback that ensures continuous coupling between phalanx specification and elongation. Our work, which links mechanical and molecular signals, provides a mechanistic context for the emergence of organizing centers that may underlie various developmental processes.

Somatic Mosaicism of a PDGFRB Activating Variant in Aneurysms of the Intracranial, Coronary, Aortic, and Radial Artery Vascular Beds.

Background Activating variants in platelet-derived growth factor receptor beta (PDGFRB), including a variant we have previously described (p.Tyr562Cys [g.149505130T>C [GRCh37/hg19]; c.1685A>G]), are associated with development of multiorgan pathology, including aneurysm formation. To investigate the association between the allele fraction genotype and histopathologic phenotype, we performed an expanded evaluation of post-mortem normal and aneurysmal tissue specimens from the previously published index patient. Methods and Results Following death due to diffuse subarachnoid hemorrhage in a patient with mosaic expression of the above PDGFRB variant, specimens from the intracranial, coronary, radial and aortic arteries were harvested. DNA was extracted and alternate allele fractions (AAF) of PDGFRB were determined using digital droplet PCR. Radiographic and histopathologic findings, together with genotype expression of PDGFRB were then correlated in aneurysmal tissue and compared to non-aneurysmal tissue. The PDGFRB variant was identified in the vertebral artery, basilar artery, and P1 segment aneurysms (AAF: 28.7%, 16.4%, and 17.8%, respectively). It was also identified in the coronary and radial artery aneurysms (AAF: 22.3% and 20.6%, respectively). In phenotypically normal intracranial and coronary artery tissues, the PDGFRB variant was not present. The PDGFRB variant was absent from lymphocyte DNA and normal tissue, confirming it to be a non-germline somatic variant. Primary cell cultures from a radial artery aneurysm localized the PDGFRB variant to CD31-, non-endothelial cells. Conclusions Constitutive expression of PDGFRB within the arterial wall is associated with the development of human fusiform aneurysms. The role of targeted therapy with tyrosine kinase inhibitors in fusiform aneurysms with PDGFRB mutations should be further studied.

Effect of FKBP12-Derived Intracellular Peptides on Rapamycin-Induced FKBP-FRB Interaction and Autophagy.

Intracellular peptides (InPeps) generated by proteasomes were previously suggested as putative natural regulators of protein-protein interactions (PPI). Here, the main aim was to investigate the intracellular effects of intracellular peptide VFDVELL (VFD7) and related peptides on PPI. The internalization of the peptides was achieved using a C-terminus covalently bound cell-penetrating peptide (cpp; YGRKKRRQRRR). The possible inhibition of PPI was investigated using a NanoBiT® luciferase structural complementation reporter system, with a pair of plasmids vectors each encoding, simultaneously, either FK506-binding protein (FKBP) or FKBP-binding domain (FRB) of mechanistic target of rapamycin complex 1 (mTORC1). The interaction of FKBP-FRB within cells occurs under rapamycin induction. Results shown that rapamycin-induced interaction between FKBP-FRB within human embryonic kidney 293 (HEK293) cells was inhibited by VFD7-cpp (10-500 nM) and FDVELLYGRKKRRQRRR (VFD6-cpp; 1-500 nM); additional VFD7-cpp derivatives were either less or not effective in inhibiting FKBP-FRB interaction induced by rapamycin. Molecular dynamics simulations suggested that selected peptides, such as VFD7-cpp, VFD6-cpp, VFAVELLYGRKKKRRQRRR (VFA7-cpp), and VFEVELLYGRKKKRRQRRR (VFA7-cpp), bind to FKBP and to FRB protein surfaces. However, only VFD7-cpp and VFD6-cpp induced changes on FKBP structure, which could help with understanding their mechanism of PPI inhibition. InPeps extracted from HEK293 cells were found mainly associated with macromolecular components (i.e., proteins and/or nucleic acids), contributing to understanding InPeps' intracellular proteolytic stability and mechanism of action-inhibiting PPI within cells. In a model of cell death induced by hypoxia-reoxygenation, VFD6-cpp (1 µM) increased the viability of mouse embryonic fibroblasts cells (MEF) expressing mTORC1-regulated autophagy-related gene 5 (Atg5), but not in autophagy-deficient MEF cells lacking the expression of Atg5. These data suggest that VFD6-cpp could have therapeutic applications reducing undesired side effects of rapamycin long-term treatments. In summary, the present report provides further evidence that InPeps have biological significance and could be valuable tools for the rational design of therapeutic molecules targeting intracellular PPI.

Corrigendum: Elena+ Care for COVID-19, a Pandemic Lifestyle Care Intervention: Intervention Design and Study Protocol.

[This corrects the article DOI: 10.3389/fpubh.2021.625640.].

Elena+ Care for COVID-19, a Pandemic Lifestyle Care Intervention: Intervention Design and Study Protocol.

Background: The current COVID-19 coronavirus pandemic is an emergency on a global scale, with huge swathes of the population required to remain indoors for prolonged periods to tackle the virus. In this new context, individuals' health-promoting routines are under greater strain, contributing to poorer mental and physical health. Additionally, individuals are required to keep up to date with latest health guidelines about the virus, which may be confusing in an age of social-media disinformation and shifting guidelines. To tackle these factors, we developed Elena+, a smartphone-based and conversational agent (CA) delivered pandemic lifestyle care intervention. Methods: Elena+ utilizes varied intervention components to deliver a psychoeducation-focused coaching program on the topics of: COVID-19 information, physical activity, mental health (anxiety, loneliness, mental resources), sleep and diet and nutrition. Over 43 subtopics, a CA guides individuals through content and tracks progress over time, such as changes in health outcome assessments per topic, alongside user-set behavioral intentions and user-reported actual behaviors. Ratings of the usage experience, social demographics and the user profile are also captured. Elena+ is available for public download on iOS and Android devices in English, European Spanish and Latin American Spanish with future languages and launch countries planned, and no limits on planned recruitment. Panel data methods will be used to track user progress over time in subsequent analyses. The Elena+ intervention is open-source under the Apache 2 license (MobileCoach software) and the Creative Commons 4.0 license CC BY-NC-SA (intervention logic and content), allowing future collaborations; such as cultural adaptions, integration of new sensor-related features or the development of new topics. Discussion: Digital health applications offer a low-cost and scalable route to meet challenges to public health. As Elena+ was developed by an international and interdisciplinary team in a short time frame to meet the COVID-19 pandemic, empirical data are required to discern how effective such solutions can be in meeting real world, emergent health crises. Additionally, clustering Elena+ users based on characteristics and usage behaviors could help public health practitioners understand how population-level digital health interventions can reach at-risk and sub-populations.

High levels of connectivity over large distances in the diadematid sea urchin Centrostephanus sylviae.

Most benthic marine invertebrates with sedentary benthic adult phases have planktonic larvae that permit connectivity between geographically isolated populations. Planktonic larval duration and oceanographic processes are vital to connecting populations of species inhabiting remote and distant islands. In the present study, we analyzed the population genetic structure of the sea urchin Centrostephanus sylviae, which inhabits only the Juan Fernández Archipelago and the Desventuradas islands, separated by more than 800 km. For 92 individuals collected from Robinson Crusoe and Selkirk Islands (Juan Fernández Archipelago) and San Ambrosio Island (Desventuradas Islands), 7,067 single nucleotide polymorphisms (SNPs) were obtained. The results did not show a spatial genetic structure for C. sylviae; relative high migration rates were revealed between the islands. An analysis of the water circulation pattern in the area described a predominant northward water flow with periods of inverted flow, suggesting that larvae could move in both directions. Overall, this evidence suggests that C. sylviae comprises a single large population composed of individuals separated by more than 800 km.

Peptidomic profiling of cerebrospinal fluid from patients with intracranial saccular aneurysms.

Intracranial saccular aneurysms (ISA) represent 90%-95% of all intracranial aneurysm cases, characterizing abnormal pockets at arterial branch points. Ruptures lead to subarachnoid hemorrhages (SAH) and poor prognoses. We applied mass spectrometry-based peptidomics to investigate the peptidome of twelve cerebrospinal fluid (CSF) samples collected from eleven patients diagnosed with ISA. For peptide profile analyses, participants were classified into: 1) ruptured intracranial saccular aneurysms (RIA), 2) unruptured intracranial saccular aneurysms (UIA), and late-ruptured intracranial saccular aneurysms (LRIA). Altogether, a total of 2199 peptides were detected by both Mascot and Peaks software, from which 484 (22.0%) were unique peptides. All unique peptides presented conserved chains, domains, regions of protein modulation and/or post-translational modification sites related to human diseases. Gene Ontology (GO) analyses of peptide precursor proteins showed that 42% are involved in binding, 56% in cellular anatomical entities, and 39% in intercellular signaling molecules. Unique peptides identified in patients diagnosed with RIA have a larger molecular weight and a distinctive developmental process compared to UIA and LRIA (P ≤ 0.05). Continued investigations will allow the characterization of the biological and clinical significance of the peptides identified in the present study, as well as identify prototypes for peptide-based pharmacological therapies to treat ISA. SIGNIFICANCE.

Phosphoproteomic and Kinomic Signature of Clinically Aggressive Grade I (1.5) Meningiomas Reveals RB1 Signaling as a Novel Mediator and Biomarker.

PURPOSE: Most World Health Organization (WHO) grade I meningiomas carry a favorable prognosis. Some become clinically aggressive with recurrence, invasion, and resistance to conventional therapies (grade 1.5; recurrent/progressive WHO grade I tumors requiring further treatment within 10 years). We aimed to identify biomarker signatures in grade 1.5 meningiomas where histopathology and genetic evaluation has fallen short. EXPERIMENTAL DESIGN: Mass spectrometry (MS)-based phosphoproteomics and peptide chip array kinomics were used to compare grade I and 1.5 tumors. Ingenuity Pathway Analysis (IPA) identified alterations in signaling pathways with validation by Western blot analysis. The selected biomarker was evaluated in an independent cohort of 140 samples (79/140 genotyped for meningioma mutations) by tissue microarray and correlated with clinical variables. RESULTS: The MS-based phosphoproteomics revealed differential Ser/Thr phosphorylation in 32 phosphopeptides. The kinomic profiling by peptide chip array identified 10 phosphopeptides, including a 360% increase in phosphorylation of RB1, in the 1.5 group. IPA of the combined datasets and Western blot validation revealed regulation of AKT and cell-cycle checkpoint cascades. RB1 hyperphosphorylation at the S780 site distinguished grade 1.5 meningiomas in an independent cohort of 140 samples and was associated with decreased progression/recurrence-free survival. Mutations in NF2, TRAF7, SMO, KLF4, and AKT1 E17K did not predict RB1 S780 staining or progression in grade 1.5 meningiomas. CONCLUSIONS: RB1 S780 staining distinguishes grade 1.5 meningiomas, independent of histology, subtype, WHO grade, or genotype. This promising biomarker for risk stratification of histologically bland WHO grade I meningiomas provides insight into the pathways of oncogenesis driving these outlying clinically aggressive tumors.

Somatic PDGFRB Activating Variants in Fusiform Cerebral Aneurysms.

The role of somatic genetic variants in the pathogenesis of intracranial-aneurysm formation is unknown. We identified a 23-year-old man with progressive, right-sided intracranial aneurysms, ipsilateral to an impressive cutaneous phenotype. The index individual underwent a series of genetic evaluations for known connective-tissue disorders, but the evaluations were unrevealing. Paired-sample exome sequencing between blood and fibroblasts derived from the diseased areas detected a single novel variant predicted to cause a p.Tyr562Cys (g.149505130T>C [GRCh37/hg19]; c.1685A>G) change within the platelet-derived growth factor receptor ß gene (PDGFRB), a juxtamembrane-coding region. Variant-allele fractions ranged from 18.75% to 53.33% within histologically abnormal tissue, suggesting post-zygotic or somatic mosaicism. In an independent cohort of aneurysm specimens, we detected somatic-activating PDGFRB variants in the juxtamembrane domain or the kinase activation loop in 4/6 fusiform aneurysms (and 0/38 saccular aneurysms; Fisher's exact test, p < 0.001). PDGFRB-variant, but not wild-type, patient cells were found to have overactive auto-phosphorylation with downstream activation of ERK, SRC, and AKT. The expression of discovered variants demonstrated non-ligand-dependent auto-phosphorylation, responsive to the kinase inhibitor sunitinib. Somatic gain-of-function variants in PDGFRB are a novel mechanism in the pathophysiology of fusiform cerebral aneurysms and suggest a potential role for targeted therapy with kinase inhibitors.

The impact of fishing on a highly vulnerable ecosystem, the case of Juan Fernández Ridge ecosystem.

The Juan Fernández Ridge (JFRE) is a vulnerable marine ecosystem (VME) located off the coast of central Chile formed by the Juan Fernández Archipelago and a group of seamounts. This ecosystem has unique biological and oceanographic features, characterized by: small geographical units, high degree of endemism with a high degree of connectivity within the system. Two fleets have historically operated in this system: a long term coastal artisanal fishery associated with the Islands, focused mainly on lobster, and a mainland based industrial demersal finfish fishery operating on the seamounts which is currently considered overexploited. The management of these fisheries has been based on a classical single-species approach to determine output controls (industrial fleet) and a mixed management system with formal and informal components (artisanal fleet). There has been growing interest in increasing the exploitation of fisheries, and modernization of the fishing fleet already operating in the JFRE. Under this scenario of increased levels of fishing exploitation and the high level of interrelation of species it might be necessary to understand the impact of these fisheries from a holistic perspective based on a ecosystem-based modeling approach. To address these challenges we developed an Atlantis end-to-end model was configured for this ecosystem. The implemented model has a high degree of skill in representing the observed trends and fluctuations of the JFRE. The model shows that the industrial fishing has a localized impact and the artisanal fisheries have a relatively low impact on the ecosystem, mainly via the lobster fishery. The model indicates that the depletion of large sized lobster has leads to an increase in the population of sea urchins. Although this increase is not sufficient, as yet, to cause substantial flow-on effects to other groups, caution is advised in case extra pressure leads the ecosystem towards a regime shift.

Kinome and phosphoproteome of high-grade meningiomas reveal AKAP12 as a central regulator of aggressiveness and its possible role in progression.

There is a need to better understand meningioma oncogenesis for biomarker discovery and development of targeted therapies. Histological or genetic criteria do not accurately predict aggressiveness. Post-translational studies in meningioma progression are lacking. In the present work, we introduce a combination of mass spectrometry-based phosphoproteomics and peptide array kinomics to profile atypical and anaplastic (high-grade) meningiomas. In the discovery set of fresh-frozen tissue specimens (14), the A-kinase anchor protein 12 (AKAP12) protein was found downregulated across the grades. AKAP12 knockdown in benign meningioma cells SF4433 increases proliferation, cell cycle, migration, invasion, and confers an anaplastic profile. Differentially regulated pathways were characteristic of high-grade meningiomas. Low AKAP12 expression in a larger cohort of patients (75) characterized tumor invasiveness, recurrence, and progression, indicating its potential as a prognostic biomarker. These results demonstrate AKAP12 as a central regulator of meningioma aggressiveness with a possible role in progression.

The Dlx5-FGF10 signaling cascade controls cranial neural crest and myoblast interaction during oropharyngeal patterning and development.

Craniofacial development depends on cell-cell interactions, coordinated cellular movement and differentiation under the control of regulatory gene networks, which include the distal-less (Dlx) gene family. However, the functional significance of Dlx5 in patterning the oropharyngeal region has remained unknown. Here, we show that loss of Dlx5 leads to a shortened soft palate and an absence of the levator veli palatini, palatopharyngeus and palatoglossus muscles that are derived from the 4th pharyngeal arch (PA); however, the tensor veli palatini, derived from the 1st PA, is unaffected. Dlx5-positive cranial neural crest (CNC) cells are in direct contact with myoblasts derived from the pharyngeal mesoderm, and Dlx5 disruption leads to altered proliferation and apoptosis of CNC and muscle progenitor cells. Moreover, the FGF10 pathway is downregulated in Dlx5-/- mice, and activation of FGF10 signaling rescues CNC cell proliferation and myogenic differentiation in these mutant mice. Collectively, our results indicate that Dlx5 plays crucial roles in the patterning of the oropharyngeal region and development of muscles derived from the 4th PA mesoderm in the soft palate, likely via interactions between CNC-derived and myogenic progenitor cells.

Comparative Proteomic Profiling Using Two-Dimensional Gel Electrophoresis and Identification via LC-MS/MS Reveals Novel Protein Biomarkers to Identify Aggressive Subtypes of WHO Grade I Meningioma.

Background Meningomas represent the most common primary intracranial tumor. The majority are benign World Health Organization (WHO) Grade I lesions, but a subset of these behave in an aggressive manner. Protein biomarkers are needed to distinguish aggressive from benign Grade I lesions. Materials and Methods Pooled protein lysates were derived from five clinically aggressive Grade I and five typically benign WHO Grade I tumors snap frozen at the time of surgery. Proteins were separated in each group using two-dimensional gel electrophoresis (2DGE) and protein spots of interest were identified using liquid chromatography-mass spectrometry (LC-MS). Potential biomarker candidates were validated using western blot assays in individual tumor samples and by tissue microarray (TMA). Results Seven candidate biomarkers were obtained from the 2DGE and validated via western blot and TMA. Biomarker validation data allowed for the creation of predictive models using binary logistical regression that correctly identified 85.9% of aggressive tumors within the larger cohort of Grade I meningioma. Conclusion Simple protein separation by 2DGE and identification of candidate biomarkers by LC-MS allowed for the identification of seven candidate biomarkers that when used in predictive models accurately distinguish aggressive from benign behavior in WHO Grade I meningioma.

Kinase Activity in Recurring Primary Skull Base Chordomas and Chondrosarcomas: Identification of Novel Pathways of Oncogenesis and Potential Drug Targets.

BACKGROUND: Chordomas and chondrosarcomas can occur in the skull base. Currently, 45% of chordomas and 56% of chondrosarcomas recur within 5 years of surgery. The role of adjuvant therapy is highly debated. No pharmacotherapies have been approved by the U.S. Food and Drug Administration for chordomas or chondrosarcomas. High propensity for recurrence and lack of definitive adjuvant therapy necessitate additional basic science research to identify molecular anomalies associated with recurrent disease. METHODS: We pooled tumor lysates from patients based on clinical criteria into 4 groups: primary chordomas, primary chordomas that recurred, primary chondrosarcomas, and primary chondrosarcomas that recurred. We used a peptide labeling method, isobaric tags for relative and absolute quantitation, to uniquely identify each tumor group. Phosphorylated peptides were identified and quantified via mass spectroscopy to determine and predict active kinases. RESULTS: Six groups of phosphorylated peptides were associated with primary tumors that later recurred. Specific kinases associated with primary chordomas that recurred were FES and FER. Specific kinases associated with primary chondrosarcomas that recurred were FES, FER, SRC family kinases, PKC, ROCK, and mitogen-activated protein kinase signaling (JNK, ERK1, p38). CONCLUSIONS: These data provide clinicians with a means to screen skull base chordomas and chondrosarcomas to help identify tumors with a propensity to recur. Many of these kinases can be efficaciously inhibited by Food and Drug Administration-approved drugs that have not yet been used in clinical trials for treatment of skull base chordomas or chondrosarcomas. Validation of kinases identified in this study may advance treatment options for patients with these tumors.

Cellular and molecular mechanisms of tooth root development.

The tooth root is an integral, functionally important part of our dentition. The formation of a functional root depends on epithelial-mesenchymal interactions and integration of the root with the jaw bone, blood supply and nerve innervations. The root development process therefore offers an attractive model for investigating organogenesis. Understanding how roots develop and how they can be bioengineered is also of great interest in the field of regenerative medicine. Here, we discuss recent advances in understanding the cellular and molecular mechanisms underlying tooth root formation. We review the function of cellular structure and components such as Hertwig's epithelial root sheath, cranial neural crest cells and stem cells residing in developing and adult teeth. We also highlight how complex signaling networks together with multiple transcription factors mediate tissue-tissue interactions that guide root development. Finally, we discuss the possible role of stem cells in establishing the crown-to-root transition, and provide an overview of root malformations and diseases in humans.

Loss of intratumoral macroscopic fat in renal angiomyolipoma following chemoradiation therapy for pancreatic cancer.

Angiomyolipoma (AML) is the most common benign mesenchymal tumour of the kidney. Classically, AML can readily be diagnosed by identifying the negatively attenuating intratumoral macroscopic fat component on non-enhanced CT scans. However, intratumoral macroscopic fat may not be visible on CT scans, mimicking renal cell carcinoma. We report a case of renal AML with CT scan evidence of macroscopic intratumoral fat that was not readily visible on subsequent CT or MRI, presumably owing to a generalized rapid loss of adipose tissue due to cachexia in a patient with pancreatic adenocarcinoma. Radiologists should be aware that AML may lose its intratumoral fat on follow-up imaging and may simulate renal cell carcinoma.