Biology subjects

Nguyen, T.

Publications and source records attributed to Nguyen, T..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Bayesian Parameter Balancing Enables Robust and Consistent Estimation of Kinetic Parameter Uncertainty

MotivationKinetic models are central to systems biology, but enzyme-kinetic parameters compiled from the literature and databases are often incomplete, inconsistent, and measured under heterogeneous conditions. Classical parameter balancing helps infer missing parameters, yet it often lacks calibrated uncertainty, robustness to misspecification, and explicit treatment of source-level heterogeneity. ResultsWe develop a formal Bayesian parameter balancing framework that enforces thermodynamic constraints, estimates full posterior uncertainty, and validates calibration using leave-one-out cross-validation and posterior-predictive coverage. Beyond the classical Gaussian formulation, we introduce robust Student-t and skewed error models to improve reliability under outliers and model misspecification, and incorporate random effects to account for source-level or group-level variability across studies. The resulting approach yields thermodynamically consistent parameter sets with well-calibrated credible intervals on held-out data, offering a Bayesian parameter balancing approach useful to systems biology researchers. Availability and implementationSource code, data, workflows, a Julia package and command-line usage are available at the project GitHub repository. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/726043v2_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@182b3c2org.highwire.dtl.DTLVardef@1e79bdforg.highwire.dtl.DTLVardef@aa56a7org.highwire.dtl.DTLVardef@11f2de2_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2026

Distinct positional identity at the center of the caudal fin establishes forked shape

The morphogenesis of complex vertebrate appendages requires precise regulation of growth, governed by distinct positional identities. The zebrafish caudal fin achieves a symmetrical, forked morphology through the regional specialization of the bony rays: peripheral rays are composed of relatively long, thick segments; while the central rays are made up of shorter, thinner segments, and their overall length is restricted. This length differential establishes the definitive forked shape of the organ. We asked whether these regional morphological differences reflect distinct underlying positional identities. Transcriptomic profiling of intact tissues from adult wild-type zebrafish suggested that central rays possess unique expression profiles, distinct from those of peripheral rays. We previously identified a treatment during embryogenesis that allows excess growth in the central rays, creating a truncate fin shape in adults-we asked whether this novel fin shape was caused by a peripheralization of the central rays. Indeed, the central rays of truncate fins were not only longer, but were composed of longer and thicker individual segments, reminiscent of peripheral rays. Further, gene expression in the central regions of truncate backgrounds showed signatures of peripheral identity. During development of the truncate phenotype, peripheral markers became expressed in more central domains of the growing truncate caudal fin, and in the supportive endoskeleton, the central hypural diastema was lost from the earliest stages. Ultimately, our results demonstrate how adult morphologies may be altered by shifts in positional identities. These findings clarify the anatomical patterning and molecular profiles that underlie regional specialization during caudal fin development.

developmental biology↗

bioRxiv2026

A multiomic lifespan signature in genetically diverse, diet-restricted mice

Dietary restriction extends lifespan across model organisms, but the plasma molecular changes mediating this effect remain incompletely characterized. We present a longitudinal multiomic analysis of 2,234 plasma samples from 960 Diversity Outbred mice subjected to intermittent fasting or caloric restriction and followed to natural death. Using mass spectrometry, we quantified 1,512 metabolites, lipids, and proteins and mapped their associations with diet, age and longevity. DR-induced molecular changes scale with caloric intake and modulate inflammatory, lipid catabolism, and oxidative stress pathways. Aging showed a biphasic signature with sharp acceleration beyond 85% of lifespan, demarcating terminal decline. Mediation and survival modeling both identified superoxide dismutase (SODE) and vascular cell adhesion molecule (VCAM1) as top lifespan predictors. Genetic analysis revealed 9,599 QTL, nine of which coincided with previously identified lifespan QTLs, and were largely related to immune regulation. These findings provide a rich multiomic and genetic resource for the aging research community.

systems biology↗

bioRxiv2026

Physical restraint induces conditioned place aversion and region-specific c-Fos activation in mice

Linking environmental contexts with stressful experiences is critical for engaging adaptive responses necessary to avoid future threats. Yet, active context-dependent avoidance remains poorly understood. Here, we establish a restraint-induced conditioned place aversion (CPA) paradigm to examine how an acute physiological stressor acquires negative motivational value through contextual association. We found that mice repeatedly exposed to physical restraint in a contextually distinguishable chamber later avoid that location, demonstrating that restraint stress can drive learned aversion in the absence of continued exposure. To identify potential neuronal correlates underlying this learned association, we quantified c-Fos expression in several areas implicated in aversive motivation, emotional salience, and contextual encoding. We found that restraint within the context of the CPA paradigm was associated with increased c-Fos in the nucleus accumbens (NAc) and basolateral amygdala (BLA) while c-Fos expression increased in the ventral hippocampus in response to exposure to the contextual cues alone. These findings reveal region-specific activation in response to restraint stress and associated contextual cues. By connecting classical stress models and associative learning, this work provides a potential platform for further investigation of the neural mechanisms underlying stress-related negative affect and avoidance behaviors.

neuroscience↗

bioRxiv2026

Redesign of energetically frustrated regions rescues function in defective T4 clamp loaders

DNA polymerase clamp loaders are AAA+ ATPases that load sliding clamps on DNA for high- speed replication. Using a platform for high-throughput mutagenesis of replication proteins in T4 bacteriophage, we carried out saturation mutagenesis of the AAA+ ATPase module of the T4 clamp loader bearing a mutation, Gln 118{lozenge}Asn (Q118N), that reduces fitness. We identified residues for which different mutations improve the fitness of the Q118N variant but are neutral in the wild-type background. These conditionally neutral "rescue hotspots" overlap with those identified earlier in another defective variant (D110C). These rescue hotspots localize to regions where the sequence is not optimal for the structure, as determined by energetic frustration analysis. We designed new sequences for three of these regions, using the protein-design algorithm ProteinMPNN. In two helical regions, several designed sequences increased the fitness of both wild-type and mutant proteins, likely due to enhanced stability. An inter-domain hinge in AAA+ module changes conformation during activation, and designs for the hinge lead to loss of fitness in the wild-type background. However, when using the active conformation as the template, designs for the hinge increase the fitness of defective variants. In contrast designs templated on the inactive conformation led to loss of fitness, suggesting that a proper conformational balance is crucial. Thus, adaptive capacity in the clamp loader resides in a network of conditionally neutral sites that enable functional tuning through shifts in stability and conformational equilibria.

biochemistry↗

bioRxiv2026

Stress-Responsive Protein IFRD1 Protects Assembled Ribosomes via a Ribosome-Salvaging Mechanism

The ability of epithelial cells to cope with injury and undergo regeneration depends on tightly coordinated cellular responses. IFRD1 is a stress-responsive protein that is evolutionarily conserved and required for the cellular regeneration program paligenosis; however, how IFRD1 works in paligenosis is not known. Here we demonstrate that IFRD1 is primarily a cytosolic ribosome-binding protein, specifically binding 80S monosomes that are not actively engaged in translation. Using multiple in vivo and in vitro injury models, including cerulein-induced pancreatitis in mice and tunicamycin-induced ER stress in cell culture, we demonstrate that IFRD1 acts as a ribosome-salvaging factor, preventing ribosomes from degradation. In the absence of IFRD1 during ER stress, non-translating 80S ribosomes were unstable and prone to disassembly and selective degradation. The resulting accumulation of degraded ribosomal subunits overwhelmed cellular autophagic machinery, as evidenced by accumulation of the autophagy-tagging protein p62, even though overall autophagic flux remained unaffected. Ultimately, cells lacking IFRD1 showed reduced mTORC1 activity followed by increased cell death, consistent with patterns observed in cells lacking IFRD1 during paligenosis. Thus, we detail a previously unrecognized cellular function for IFRD1 in stabilizing and preserving the mature ribosome pool during metabolic and translational transitions such as paligenosis.

cell biology↗

bioRxiv2026

Monocyte Migration Emerges from a Divergent Chemokine Signaling Network

Migration of leukocytes in the context of immune homeostasis or inflammatory diseases is regulated by activation of chemokine receptors by chemokine ligands. To elucidate how these interactions give rise to cell migration, we mapped the chemokine-stimulated signal transduction network in monocytic THP-1 cells. Global phosphoproteomics revealed 630 time-resolved changes in phosphorylated proteins downstream of the chemokine receptor CCR2. We used the "PHONEMeS" network modeling algorithm to generate the most parsimonious signal transduction network consistent with the observed protein phosphorylation data. The CCR2 signaling network is highly divergent, acting via multiple branches to regulate proteins required for cell migration. We validated this model using kinase inhibitors targeting different branches of the network and successfully blocked chemokine-stimulated cell migration. Thus, chemotaxis is an emergent property resulting from an integrated cellular response to divergent signaling pathways. This paradigm suggests that physiological regulation or pharmacological blockade of chemokine-driven inflammation could potentially be achieved by inhibiting any of the divergent pathways within the network.

systems biology↗

bioRxiv2026

BRD4 recruitment desilences transcription without erasure or depletion of repressive chromatin

How genes are desilenced within mesoscale repressive chromatin is a crucial yet poorly understood phenomenon. Prevailing models posit that methylation of lysine-9 of histone H3 (H3K9me3) engages heterochromatin protein 1 (HP1) to drive chromatin compaction and transcriptional silencing. The erasure of this repressive mark and its replacement with acetyl/acyl groups recruits positive factors such as BRD4/BET to elicit gene transcription. We report that in Friedreichs ataxia, a synthetic gene regulator (SynGR1) drives transcription across repressive chromatin without removal or replacement of H3K9me3 or HP1. By selectively recruiting BRD4/BET into repressive GAA-repeats in frataxin (FXN), SynGR1 creates a paradoxical state where gene transcription and repressive chromatin co-exist. Contrary to convention, we find that BRD4 readily partitions into phase separated HP1 condensates in vitro and into HP1 puncta in patient-derived cells, thus presenting a mechanistic explanation for desilencing transcription without the dispersal of mesoscale repressive chromatin. Epigenetic drugs that gate sequential steps in transcription, synergistically stimulate FXN expression while concomitantly increasing, rather than eliminating, repressive H3K9me3 and HP1 levels. More broadly, this study highlights the dynamic nature of repressive chromatin and the context-dependence of epigenetic marks in regulating gene expression.

cell biology↗

bioRxiv2026

The Role of Meningeal Lymphatic Vessels and Perivascular Cerebrospinal Fluid Flow in Age-Related Processing Speed Decline

Meningeal lymphatic vessels (mLV) play essential roles in draining cerebrospinal fluid (CSF) into peripheral blood. The mLVs are hypothesized to be supportive structures to the glymphatic system, which is thought to remove metabolic byproducts from brain parenchyma and has been most directly studied in rodent models. Previous rodent studies have indicated a correlation between mLV function and cognitive performance, but this relationship in humans remains unexplored. Age-related declines in glymphatic system efficiency in humans and cognitive performance have been observed separately. This study investigates age- and sex-related differences in CSF production via choroid plexus volumes, mLV characteristics, and glymphatic system efficiency, overall elucidating the implication of cerebral lymphatic function on cognition. We recruited 26 healthy adults from Dallas-Fort Worth and acquired magnetic resonance images. mLVs along the sagittal sinus were visualized and segmented from T2-FLAIR images. The glymphatic system was evaluated by measuring diffusivity along the perivascular space. Choroid plexus volume and brain volume were estimated from T1-MPRAGE. Neuropsychological tests were conducted to assess cognitive function. Our findings indicate that glymphatic function diminishes with age, while mLV and choroid plexus volumes increase. Males displayed greater mLV volume than females, yet no sex differences were found in glymphatic function or choroid plexus volume. Notably, mLV volume increased as glymphatic function declined, independent of age. Moreover, a glymphatic-mLV latent variable significantly predicted processing speed, underscoring the influence of cerebral lymphatics on cognition. In conclusion, this study highlights a decline in glymphatic function with age, accompanied by increased mLV volumes and altered processing speed. These lymphatic system changes may underlie or contribute to the cognitive declines observed in healthy and pathological aging. Significance StatementThe glymphatic system and meningeal lymphatic vessels play crucial roles in removing brain cell waste. The relationship between these systems and their effect on human cognition, particularly processing speed, is unknown. We demonstrate that these systems change with advancing age. Variations in cerebral lymphatic function contribute to differences in processing speed independent of age, ultimately affecting higher-order cognitive function. The findings presented have implications for cognitive function in both healthy and diseased states.

neuroscience↗

bioRxiv2026

Cell state-specific metabolic networks govern ferroptosis versus apoptosis in small cell lung cancer

Cellular heterogeneity and plasticity are hallmarks of cancer that contribute to tumor growth and therapy resistance. Here we investigated metabolic heterogeneity in small cell lung cancer (SCLC), an aggressive neuroendocrine (NE) cancer type. Through integrated transcriptomic and metabolomic analyses, we identified a universal dependency on exogenous cysteine/cystine (Cys) across all NE/non-NE SCLC cell states. Notably, NE and non-NE cells with low levels of the ASCL1 transcription factor die from ferroptosis upon Cys depletion. In contrast, ASCL1-high cells die from apoptosis but are ferroptosis resistant. This resistance to ferroptosis is driven by the direct upregulation of the gene coding for the GCH1 enzyme by ASCL1, which results in higher levels of the BH4/BH2 antioxidants. Accordingly, combining cysteine depletion with BH4/BH2 synthesis inhibition effectively reduces tumor growth in patient-derived xenografts. This work elucidates distinct metabolic states in SCLC and suggests new approaches to induce cell death in this lethal form of cancer.

cancer biology↗

bioRxiv2026

The antipsychotic drug clozapine suppresses autoimmunity driving psychosis-like behavior in mice

Antipsychotic drugs are the first-line treatment for psychosis yet their mechanism of action remains poorly understood, largely due to the challenge to faithfully model psychosis preclinically. Here, we focus on the emerging concept that psychosis can be caused by brain autoimmunity and present a novel mouse model of anti-N-methyl-D-aspartate-receptor (anti-NMDAR) encephalitis, a condition that manifests with psychosis and autoanti-bodies against the NMDAR. We devised a new mRNA-based approach to immunize mice against the NMDAR. Immunized mice developed psychosis-like behaviors that were caused by anti-NMDAR autoantibodies leading to phagocytosis of NMDARs by brain microglia. The antipsychotic drug clozapine rescued psychosis-like behaviors and, remarkably, reduced anti-NMDAR autoantibody levels and antibody-mediated phagocytosis of NMDARs. The immunomodulatory effects of clozapine were confirmed in a mouse model of systemic lupus erythematosus. Our results demonstrate that clozapine suppresses autoimmunity driving psychosis-like behaviors, raising the possibility that immunomodulation contributes to antipsychotic drug action. HIGHLIGHTSO_LImRNA immunization against the NMDAR induces psychosis-like behavior in mice C_LIO_LIAnti-NMDAR autoantibodies are sufficient for psychosis-like behavior C_LIO_LIMicroglial phagocytosis of NMDARs mediates psychosis-like behavior induced by anti-NMDAR autoanti-bodies. C_LIO_LIClozapine reduces anti-NMDAR autoantibodies, microglial phagocytosis and psychosis-like behavior, consistent with immunomodulation as a potential mechanism of antipsychotic drug action. C_LI

neuroscience↗

bioRxiv2026

A Global Ligandability Map of Tryptoline Butynamide Stereoprobes Identifies Covalent Inhibitors of the Actin Maturation Protease ACTMAP

Covalent chemistry coupled with activity-based protein profiling (ABPP) offers a versatile approach for small-molecule ligand discovery in native biological contexts. The covalent ligandability maps generated by ABPP that target cysteine have frequently leveraged the acrylamide as a reactive group due to its tempered electrophilicity and presence in many advanced tool compounds and therapeutics. More recently, alternative cysteine-directed reactive groups such as the butynamide have emerged as an additional source of covalent probes and drugs, but their global reactivity with the proteome remains largely unexplored. Here, we compare the ligandability maps of stereochemically defined acrylamide and butynamide compounds (stereoprobes) built from a common tryptoline core and find that the butynamides, despite exhibiting attenuated intrinsic and proteome-wide reactivity, preferentially engage a diverse set of proteins in human cancer cells. Among the butynamide-preferring proteins was C19orf54/ACTMAP, a cysteine protease required for the post-translational maturation of actin. We show that (1S, 3R)-tryptoline butynamides stereoselectively react with the catalytic nucleophile of ACTMAP, leading to accumulation of N-terminally unprocessed actin in cancer cells. Our findings support reactive group diversification as a strategy for expanding the ligandability of the human proteome and the butynamide, more specifically, as a differentiated cysteine-directed electrophile for chemical probe discovery.

biochemistry↗

bioRxiv2026

Mechanosensing and IL-13 Signaling Synergistically Modulate Intestinal Stem Cell Differentiation via STAT6 and YAP

A long-term complication of chronic inflammation is the mechanical stiffening of the tissue, culminating in fibrosis. Fibrosis can severely disrupt tissue function and is a major risk factor for other diseases. It is not currently well understood how fibrosis impacts the response to inflammatory signals. To address this, we investigated cross-talk between cellular mechanosensing and the response to Interleukin (IL)-13, a cytokine associated with inflammatory bowel diseases (IBDs). Using 3D intestinal organoids and organoid monolayer culture, we uncovered a synergy between mechanosensing and IL-13 signaling in regulating intestinal stem cell differentiation. Through quantitative high-resolution microscopy and functional inhibition, we found that this response requires activation of STAT6, a known mediator of IL-13. Both IL-13 and high substrate stiffness increase cellular traction forces and focal adhesion formation, but at the expense of reduced tension at cell-cell junctions and compromised epithelial barrier function. The mechanosensing and IL-13 responses require actomyosin contractility and YAP, which is activated downstream of a positive feedback loop involving STAT6-dependent myosin-2 activation. Our results establish a novel STAT6-YAP signaling axis that integrates inflammatory and mechanical cues to regulate intestinal cell fate and barrier integrity, opening new avenues to target epithelial dysfunction in fibrosis, chronic inflammation and regenerative medicine.

cell biology↗

bioRxiv2026

Developmentally programmed nuclear pore complex replacement enables oocyte specification

Oocytes endow embryos with molecular machinery essential for development, but not all maternal components are inherited indiscriminately. In Drosophila, surveillance pathways eliminate defective mitochondria and aberrant RNAs from the maternal pool. Whether stable nuclear structures, like nuclear pore complexes (NPCs), are similarly curated remains unknown. Here, we uncover a developmentally programmed NPC turnover pathway that renews NPCs during oocyte specification. NPC levels decline through a combination of passive dilution, driven by deferred nucleoporin expression, and active degradation mediated by the ESCRT-III/Vps4 pathway. This clearance is counterbalanced by subsequent de novo NPC synthesis. Failure to turn over NPCs results in aberrantly persistent germ cell gene expression and defective oocyte specification. These findings establish NPC renewal as a critical step in oocyte identity establishment and maternal provisioning.

developmental biology↗

bioRxiv2026

IDH-mutant inhibitors enhance the sensitivity of IDH1-mutant gliomas to cysteine-methionine deprivation and ferroptosis

Cysteine is essential for synthesizing glutathione, the brains main antioxidant, and cysteine deprivation can trigger ferroptosis. Here, using a new mouse model of IDH1-mutant glioma that recapitulates the characteristics of human IDH1-mutant low-grade gliomas, we demonstrate that IDH1-mutant glioma cells are significantly more vulnerable to cysteine deprivation alone or in combination with the ferroptosis inducer RSL3, compared to IDH1-wildtype glioma cells. In addition, treatments with the IDH-mutant inhibitors vorasidenib and ivosidenib further sensitize the cells to ferroptosis. Metabolomics analysis reveals that IDH1-mutant cells have altered cysteine and methionine metabolism with deficiency in transsulfuration, which is further exacerbated by cysteine-methionine deprivation and IDH-mutant inhibitors. Furthermore, dietary cysteine-methionine deprivation alone or in combination with convection-enhanced delivery of RSL3 or ivosidenib in vivo significantly prolongs survival of IDH1-mutant tumor-bearing mice. Our findings suggest that targeting cysteine and methionine metabolism in combination with IDH-mutant inhibition provides promising therapeutic strategies for IDH1-mutant gliomas.

cancer biology↗

bioRxiv2026

The structure of the native cardiac crossbridge in the rigor state.

Cardiac contraction is driven by double-headed myosin cycling on cardiac thin filaments, where troponin-tropomyosin regulates myosin access to actin. Prior research used a single-headed myosin bound to bare actin, thereby limiting insight into coordination between myosin heads and the influence of troponin-tropomyosin on actomyosin interactions. Here, we report a high-resolution structure of the native cardiac rigor cross-bridge formed by heavy meromyosin bound to the thin filament. We show that direct communication between the two bound heads, uneven interactions between the heads and tropomyosin, and spatial constraints imposed by troponin govern myosin placement along the thin filament. Additionally, the two heads display non-equivalent motor-light chain interactions, yielding distinct lever-arm conformations indicative of asymmetric intramolecular strain. Together, these findings provide a structural framework for how the two myosin heads coordinate and how the components of the thin filament are integrated into force generation by active cross-bridges.

biophysics↗

bioRxiv2026

Non-viral vasculogenic reprogramming restores cognition and mitigates pathology in Alzheimer's disease

Alzheimers Disease (AD) is characterized by progressive cognitive decline associated with amyloid-beta (A{beta}) plaques, neurofibrillaiy tangles, inflammation, synaptic loss, and profuse neuronal death. Accumulating evidence demonstrates that cerebrovascular impairment precedes the emergence of neuropathological hallmarks, implicating vascular dysfunction as an early contributor to AD onset and progression. We investigated a non-viral strategy to generate pro-vasculogenic fibroblasts by transiently overexpressing Et{upsilon}2, Foxc2, and Flii (EFF) as a potential cell-based therapy for neurovascular deficits in AD. To assess therapeutic potential, FFF-primc[d] fibroblasts were injected into a mouse model of AD (3xTg-AD) and wild-type controls via the intracerebroventricular (ICV) route, followed by cognitive assessments and subsequent brain tissue analyses. Our findings demonstrate that FFF-primed fibroblasts acquire vasculogenic properties, enhance cerebral blood flow (CBF), and alleviate spatial memory deficits in 3xTg-AD mice. Moreover, transplanted FFF-primed fibroblasts exhibited long-term survival, integrated into the brain vasculature, and promoted cortical vascular remodeling in the AD brain. Notably, ICV deployment of these cells is also correlated with reduced cortical amyloid-beta load, suggesting potential therapeutic benefits in reducing AD pathology. Transcriptomic analysis identified the activation of genes involved in fatty acid oxidation, such as Ppar, known for its anti-amyloidogenic and anti-inflammatory effects. Collectively, these findings highlight non- viral, reprogramming-based vasculogenic cell therapy as a promising strategy for Alzheimers disease, capable of alleviating cognitive decline and addressing AD pathology across cellular and tissue scales.

neuroscience↗

bioRxiv2026

PU.1 inhibition sensitizes stem-monocytic AML to BCL2 blockade

Acute myeloid leukemia (AML) exhibits substantial transcriptional heterogeneity across differentiation states that influences therapeutic response to BCL2 inhibition with venetoclax. While hematopoietic stem cell (HSC)-like AMLs show high sensitivity to venetoclax and monocytic-like AMLs demonstrate resistance, the therapeutic behavior of leukemias harboring both transcriptional programs remains poorly defined. Analysis of a large AML cohort reveals a distinct patient population exhibiting concurrent HSC- and monocyte-like transcriptional signatures, which we term stem-monocytic AML. Ex vivo drug sensitivity profiling demonstrates that stem-monocytic AMLs exhibit venetoclax resistance comparable to pure monocytic disease, despite expressing HSC-like transcriptional features. Using a leukemia cell line model that recapitulates stem-monocytic AML characteristics, we show through immunophenotyping and single-cell lineage tracing that venetoclax preferentially depletes immature blasts while sparing differentiated monocytic populations. Single-cell transcriptomic and chromatin accessibility analyses identify enrichment of myeloid differentiation transcription factors, particularly PU.1, in resistant populations. A targeted CRISPR knockout screen confirms that PU.1 disruption induces differentiation arrest and enhances venetoclax sensitivity primarily in the immature immunophenotypic compartments. Pharmacologic PU.1 inhibition with the small molecule DB2313 synergizes with venetoclax in both cell line models and primary patient samples. These findings establish stem-monocytic AML as a transcriptionally and functionally distinct subtype and nominate combined PU.1 and BCL2 inhibition as a rational therapeutic strategy for improving venetoclax response in this patient population.

cancer biology↗