OBJECTIVE:The objective of this study was to provide clinical and pathological characterization, and evaluation of the diagnostic and prognostic implications of levodopa response in Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). METHODS:Long-duration levodopa response in patients with pathology-confirmed PD, MSA, and PSP was collated from medical records. Associations between definite levodopa response (>50% motor improvement sustained >2 years) with clinical and pathological features were reported. Risk of disease milestones using multivariate Cox regression and diagnostic accuracy parameters were estimated for several measures of levodopa response. RESULTS:Fourteen percent of 132 patients with PD (57.1% men, age at onset 60.0 ± 11.8 years) did not have a definite levodopa response associated with older age and postural-instability and gait-difficulty subtype without global or nigral pathological differences. Definite levodopa responders had 55% lower falls, 69% lower dementia risk, and 69% increased survival. Eight percent of 115 patients with MSA (55.7% men, age at onset 57.9 ± 10.4 years) showed a definite levodopa response without distinctive clinical or pathological features, and no impact on disease milestones. Two percent of 191 patients with PSP (64.4% men, age of onset 67.6 ± 7.6 years) showed a definite levodopa response associated with a PSP-parkinsonism subtype, and more frequent and severe Lewy copathology. Definite levodopa response showed excellent diagnostic accuracy (sensitivity 86.4% and specificity 95.8%) to distinguish PD from MSA and PSP. Short-duration (acute dopaminergic drug challenge) response had suboptimal diagnostic value and modest correlation with long-duration response. INTERPRETATION:Levodopa response in PD, MSA, and PSP has important clinical, pathological, diagnostic, and prognostic implications. ANN NEUROL 2026;100:305-318.

Progressive supranuclear palsy (PSP) is a heterogeneous neurodegenerative disease characterized by the accumulation of misfolded 4-repeat tau within neurons and glial cells. There are limited longitudinal data on pathologically confirmed PSP patients with phenotypes other than classic Richardson's syndrome (RS) and the pathomechanisms responsible for the broad variability in clinical phenotype and progression are not well understood. An unresolved question in this context is whether distinct spatiotemporal patterns of tau pathology propagation exist within the clinicopathological spectrum of PSP. We included 241 consecutive, pathologically confirmed patients with PSP from the Queen Square Brain Bank for Neurological Disorders (2010-2022). Phenotyping was performed based on clinical features present within the first 3 years from symptom onset according to the Movement Disorder Society (MDS) criteria, and specific clinical features and disease milestones were recorded. Genotyping was performed using Illumina NeuroBooster and NeuroChip arrays and MAPT haplotype, APOE genotype, TRIM11 rs564309 and SLC2A13 rs2242367 single nucleotide polymorphism data were collated. Tissue sections from eight brain regions, mounted on glass slides, were immunostained for hyperphosphorylated tau and digitized using whole-slide scanning. Forty-one anatomical regions of interest were manually segmented, and total tau pathology burden was quantified using an automated, machine learning-based algorithm. The associations between survival and both clinicogenetic features and regional tau pathology burden were modelled using Cox regression and generalized linear models, respectively, and the Subtype and Stage Inference (SuStaIn) algorithm was used to identify subgroups with distinct progression patterns. We have identified: (i) several clinical predictors of survival in PSP and the relationship between regional tau pathology burden and survival; (ii) novel anatomical reference standards for the expected distribution of tau pathology across MDS-defined PSP phenotypes, including region-specific white matter involvement in patients with corticobasal syndrome and speech/language variants; (iii) associations potentially linking biological sex, MAPT haplotype and TAR DNA-binding protein 43 (TDP-43) co-pathology to clinical phenotype and regional tau pathology burden; (iv) patterns of covariance in regional tau pathology implicating inter-regional connectivity in tau spreading; and (v) three distinct spatiotemporal patterns of tau pathology progression: one characterized by initial involvement of subcortical grey matter followed by rostral spread to cortical regions and two characterized by early, simultaneous involvement of subcortical grey matter and cortical regions. Taken together, these results indicate that PSP clinicopathological heterogeneity is mediated by propagation of tau pathology along anatomically connected networks and via intrinsic regional susceptibility mechanisms, possibly influenced by sex, genetic factors and co-pathology.

Corticobasal degeneration (CBD) is a late onset progressive neurodegenerative condition of the 4-repeat-tauopathy-type, classically presenting with asymmetrical rigidity, dystonia and myoclonus. In the most recent diagnostic criteria, Armstrong and colleagues (2013) described four clinical phenotypes associated with this pathology, including corticobasal syndrome (CBS), through a large retrospective analysis of published cases and confirmed brain bank cases of CBD. However, predicting CBD pathology remains challenging. With the advent of disease-modifying therapies, it has become particularly important to distinguish Alzheimer's disease pathology from other underlying pathologies. We therefore combined two prospectively recruited cohorts of patients with CBS and analysed their key demographic, clinical and biomarker features. We included a separate cohort from UK brain banks who were diagnosed with CBS in life. We divided patients into three groups: CBS-Alzheimer's (CBS-AD), CBS-non-Alzheimer's (CBS-non-AD) and CBS-indeterminate (CBS-IDT) based on biomarkers and pathology, comparing clinical features, regional volumetric MRI measures and Nucleic Acid-Linked Immuno-Sandwich Assay with detection by next generation sequencing (NULISAseq) blood protein levels between groups. We performed additional analyses of pathologically verified cases. We included 397 participants, of which 57.7% were female. The mean age at symptom onset was 65.9 years. AD biomarkers and pathology permitted classifying 47 (11.8%) of the cases as CBS-AD, 134 (33.8%) as CBS-non-AD and 216 (54.4%) as CBS-IDT. Patients with CBS-AD had a younger age at onset (61.8 years vs 66.1 years, P < 0.01 and less severe motor deficits (non-significantly lower scores on MDS-UPDRS and PSPRS) and more severe cognitive impairment (non-significantly lower scores on MoCA). Patients with CBS-AD had higher rates of cortical sensory impairment (P = 0.087) and lower rates of limb dystonia (P < 0.01) and falls (P < 0.01) compared to the CBS-non-AD group. Volumetric MRI analysis revealed smaller parietal lobe volumes in CBS-AD (P = 0.01). The most common pathological diagnoses were PSP, CBD and AD. Limb dystonia was more common in people with CBD and PSP pathology (P = 0.077). Falls, impaired verbal fluency and impaired vertical saccades were confirmed as more common in PSP (P = 0.046, P = 0.040, P = 0.012, respectively). In summary, younger onset, less parkinsonism and more cognitive and cortical sensory impairment, along with reduced MRI parietal volumes point to CBS-AD, while limb dystonia, falls and worse verbal fluency relate to CBS-non-AD. Clinical, imaging and blood-biomarkers in can augment the Armstrong criteria in predicting the underlying pathology of corticobasal syndromes.

BACKGROUND:Several neurodegenerative diseases can mimic the clinical presentation of progressive supranuclear palsy (PSP), limiting accurate diagnosis during life. This has important implications for clinical practice, biomarker studies, and therapeutic trial design. OBJECTIVES:To investigate whether the proportion of clinically diagnosed PSP patients with non-PSP pathology (termed 'mimics') has changed over the past 20 years since last examined in this cohort, and to identify clinical features that distinguish confirmed PSP from these mimics. METHODS:We reviewed the clinical records of pathologically confirmed PSP patients donated to the Queen Square Brain Bank from 2010 to 2022, and PSP mimics donated from 1989 to 2022. Demographic information, clinical features, and progression milestones were recorded. RESULTS:We included 236 pathologically confirmed PSP patients and 72 mimics. The main pathologies in PSP mimics were Lewy body disease (30.5%), corticobasal degeneration (23.6%), and multiple system atrophy (18.1%). A final clinical diagnosis of PSP between 2010 and 2022 had a positive predictive value of 86% for underlying PSP pathology and a false negative rate of 17%. Clinical features present in the first 3 years that favoured non-PSP pathology in this cohort include levodopa responsiveness, orthostatic hypotension, dysarthria, and a subcortical phenotype. CONCLUSIONS:Clinical diagnosis of PSP has improved since last examined in this cohort 20 years ago. Although certain clinical features may point to non-PSP pathologies, a proportion of patients are difficult to distinguish on clinical grounds alone. This should be reflected in clinical trial design, and further studies will be required to determine the utility of emerging biomarkers in this setting. © 2025 International Parkinson and Movement Disorder Society.

BACKGROUND:The longitudinal impact of cognitive impairment and Alzheimer's disease neuropathological changes (ADNC) on gait dysfunction in Parkinson's disease (PD) requires further evaluation. This study aimed to investigate the association between cognitive impairment and ADNC on gait disturbances in PD. METHODS:Retrospective cohort study of pathology-confirmed PD patients with brain donation to the Queen Square Brain Bank between 2010 and 2022. Cognitive parameters (latency to dementia, hallucinations, and cholinesterase inhibitors prescription) and gait outcomes (falls, freezing (FoG), wheelchair use, postural instability and gait difficulty subtype (PIGD)) were collected from medical records. Lewy pathology and ADNC were assessed using standard staging systems. Cox proportional and logistic regression analyses estimated the associated risk of cognitive parameters and pathological changes with gait outcomes. RESULTS:A total of 140 PD patients (mean onset 60.7 years) were included. Dementia increased risk of future falls (Hazard Ratio (HR) 0.88; 95 %CI 0.84-0.92), wheelchair dependence (HR 0.84; 95 %CI 0.78-0.89), FoG severity (Odds Ratio(OR) 0.88; 95 %CI 0.77-0.98) and the PIGD subtype (OR 0.80; 95 %CI 0.69-0.92). Hallucinations increased FoG risk (HR 0.95; 95 %CI 0.92-0.99) and the PIGD subtype (OR 0.86; 95 %CI 0.75-0.97). Global ADNC and amyloid-β deposition were associated with earlier (HR 5.17; 95 %CI 1.50-17.78) and more severe gait freezing (OR 2.13; 95 %CI 1.25-3.62). CONCLUSION:Cognitive impairment and hallucinations are risk factors for future gait disturbances and FoG in PD. Global ADNC (particularly amyloid-β deposition) likely contribute to the pathophysiology of FoG, with potential therapeutic implications.

Pathogenic hexanucleotide repeat expansions in C9orf72 are the commonest genetic cause of frontotemporal dementia and/or amyotrophic lateral sclerosis. There is growing interest in intermediate repeat expansions in C9orf72 and their relationship to a wide range of neurological presentations, including Alzheimer’s disease, Parkinson’s disease, progressive supranuclear palsy, corticobasal degeneration, and corticobasal syndromes. To assess the prevalence of intermediate C9orf72 repeat expansions in a large cohort of prospectively-recruited patients clinically diagnosed with progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and atypical parkinsonism (APS), compared with healthy controls. We also sought to replicate the association between C9orf72 repeat length and CBD in neuropathologically confirmed cases. 626 cases, including PSP (n = 366), CBS (n = 130), and APS (n = 53) from the PROSPECT study, and 77 cases with pathologically confirmed CBD were screened for intermediate repeat expansions in C9orf72 using repeat-primed PCR. These were compared to controls from the PROSPECT-M-UK study and from the 1958 Birth Cohort. There was no difference in the mean or largest allele size in any affected patient group compared with controls. A higher proportion of our affected cohort had large C9orf72 repeat expansions compared to controls, but there was no difference when comparing the frequency of intermediate expansions between affected patients and controls. There was no relationship between repeat length and age at onset, level of disability, or survival. Intermediate expansions in C9orf72 do not appear to be a genetic risk factor for PSP, CBS, CBD, or atypical parkinsonism. They are not associated with age at onset, disability, or survival in our study.

Urinary frequency, urgency and nocturia are common complaints in Parkinson's disease (PD). The hypothesis most widely proposed to explain neurogenic bladder symptoms in PD is that cell loss in the substantia nigra may cause detrusor hyperactivity due to a loss in the D1 receptor-mediated tonic inhibition of the micturition reflex, although other causes including anti-parkinsonian medication cortical effects have been considered.1 We present the clinical and pathological findings of a patient with parkinsonism who presented with prominent dysautonomia and a poor response to dopaminergic medications and was considered to have possible multiple system atrophy parkinsonism (MSA-P). Pathological examination revealed that the patient had PD with α-synuclein pathology in the Onuf's nucleus (ON).

Background and ObjectivesDegeneration of the presynaptic nigrostriatal dopaminergic system is one of the main biological features of Parkinson disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), which can be measured using single-photon emission CT imaging for diagnostic purposes. Despite its widespread use in clinical practice and research, the diagnostic properties of presynaptic nigrostriatal dopaminergic (DAT) imaging in parkinsonism have never been evaluated against the diagnostic gold standard of neuropathology. The aim of this study was to evaluate the diagnostic parameters of DAT imaging compared with pathologic diagnosis in patients with parkinsonism.MethodsRetrospective cohort study of patients with DAT imaging for the investigation of a clinically uncertain parkinsonism with brain donation between 2010 and 2021 to the Queen Square Brain Bank (London). Patients with DAT imaging for investigation of pure ataxia or dementia syndromes without parkinsonism were excluded. Those with a pathologic diagnosis of PD, MSA, PSP, or CBD were considered presynaptic dopaminergic parkinsonism, and other pathologies were considered postsynaptic for the analysis. DAT imaging was performed in routine clinical practice and visually classified by hospital nuclear medicine specialists as normal or abnormal. The results were correlated with neuropathologic diagnosis to calculate diagnostic accuracy parameters for the diagnosis of presynaptic dopaminergic parkinsonism.ResultsAll of 47 patients with PD, 41 of 42 with MSA, 68 of 73 with PSP, and 6 of 10 with CBD (sensitivity 100%, 97.6%, 93.2%, and 60%, respectively) had abnormal presynaptic dopaminergic imaging. Eight of 17 patients with presumed postsynaptic parkinsonism had abnormal scans (specificity 52.9%).DiscussionDAT imaging has very high sensitivity and negative predictive value for the diagnosis of presynaptic dopaminergic parkinsonism, particularly for PD. However, patients with CBD, and to a lesser extent PSP (of various phenotypes) and MSA (with predominant ataxia), can show normal DAT imaging. A range of other neurodegenerative disorders may have abnormal DAT scans with low specificity in the differential diagnosis of parkinsonism. DAT imaging is a useful diagnostic tool in the differential diagnosis of parkinsonism, although clinicians should be aware of its diagnostic properties and limitations.Classification of EvidenceThis study provides Class II evidence that DAT imaging does not accurately distinguish between presynaptic dopaminergic parkinsonism and non-presynaptic dopaminergic parkinsonism.

Corticobasal degeneration (CBD) is one of the primary tauopathies with a disease onset in the 5th to 7th decade. CBD is a progressive condition of unknown aetiology, which is characterised neuropathologically by neuronal loss, astrogliosis and deposition of filamentous tau inclusions, composed entirely of 4-repeat tau isoforms, in neurons and glial cells in cerebral cortical areas, basal ganglia, brainstem and cerebellar nuclei. The term CBD is now a neuropathological diagnostic one and for the canonical clinical syndrome associated with CBD neuropathological changes, the corticobasal syndrome (CBS) term is used. In addition to CBS, the clinical spectrum also includes a behavioural variant of frontotemporal dementia syndrome, speech disorders, Richardson’s syndrome and, rarely, posterior cortical syndrome. In addition to CBD, CBS can also be caused by other pathologies. A number of genetic risk factors of CBD have been identified. As specific biomarkers confirming CBD as the underlying pathology responsible for CBS or other clinical manifestations are still lacking, for a definitive diagnosis of CBD neuropathological investigation is required. Recent cryo-electron microscopic studies have proven that CBD is a distinct tauopathy associated with a unique molecular structure of the tau filaments, which firmly differentiates it from other primary tauopathies.

Anti-IgLON5 disease is a unique condition that bridges autoimmunity and neurodegeneration. Since its initial description 10 years ago, an increasing number of autopsies has led to the observation of a broader spectrum of neuropathologies underlying a particular constellation of clinical symptoms. In this study, we describe the neuropathological findings in 22 patients with anti-IgLON5 disease from 9 different European centers. In 15 patients (68

Background:Pick's disease (PiD) is a rare and predominantly sporadic form of frontotemporal dementia that is classified as a primary tauopathy. PiD is pathologically defined by argyrophilic inclusion Pick bodies and ballooned neurons in the frontal and temporal brain lobes. PiD is characterised by the presence of Pick bodies which are formed from aggregated, hyperphosphorylated, 3-repeat tau proteins, encoded by the MAPT gene. The MAPT H2 haplotype has consistently been associated with a decreased disease risk of the 4-repeat tauopathies of progressive supranuclear palsy and corticobasal degeneration, however its role in susceptibility to PiD is unclear. The primary aim of this study was to evaluate the association between MAPT H2 and risk of PiD. Methods:We established the Pick's disease International Consortium (PIC) and collected 338 (60.7% male) pathologically confirmed PiD brains from 39 sites worldwide. 1,312 neurologically healthy clinical controls were recruited from Mayo Clinic Jacksonville, FL (N=881) or Rochester, MN (N=431). For the primary analysis, subjects were directly genotyped for MAPT H1-H2 haplotype-defining variant rs8070723. In secondary analysis, we genotyped and constructed the six-variant MAPT H1 subhaplotypes (rs1467967, rs242557, rs3785883, rs2471738, rs8070723, and rs7521). Findings:Our primary analysis found that the MAPT H2 haplotype was associated with increased risk of PiD (OR: 1.35, 95% CI: 1.12-1.64 P=0.002). In secondary analysis involving H1 subhaplotypes, a protective association with PiD was observed for the H1f haplotype (0.0% vs. 1.2%, P=0.049), with a similar trend noted for H1b (OR: 0.76, 95% CI: 0.58-1.00, P=0.051). The 4-repeat tauopathy risk haplotype MAPT H1c was not associated with PiD susceptibility (OR: 0.93, 95% CI: 0.70-1.25, P=0.65). Interpretation:The PIC represents the first opportunity to perform relatively large-scale studies to enhance our understanding of the pathobiology of PiD. This study demonstrates that in contrast to its protective role in 4R tauopathies, the MAPT H2 haplotype is associated with an increased risk of PiD. This finding is critical in directing isoform-related therapeutics for tauopathies.

Mutations in ITM2B cause familial British, Danish, Chinese, and Korean dementias. In familial British dementia (FBD), a mutation in the stop codon of the ITM2B gene (also known as BRI2) causes a C-terminal cleavage fragment of the ITM2B/BRI2 protein to be extended by 11 amino acids. This fragment, termed amyloid-Bri (ABri), is highly insoluble and forms extracellular plaques in the brain. ABri plaques are accompanied by tau pathology, neuronal cell death and progressive dementia, with striking parallels to the aetiology and pathogenesis of Alzheimer’s disease. The molecular mechanisms underpinning FBD are ill-defined. Using patient-derived induced pluripotent stem cells, we show that expression of ITM2B/BRI2 is 34-fold higher in microglia than neurons and 15-fold higher in microglia compared with astrocytes. This cell-specific enrichment is supported by expression data from both mouse and human brain tissue. ITM2B/BRI2 protein levels are higher in iPSC-microglia compared with neurons and astrocytes. The ABri peptide was detected in patient iPSC-derived microglial lysates and conditioned media but was undetectable in patient-derived neurons and control microglia. The pathological examination of post-mortem tissue supports the presence of ABri in microglia that are in proximity to pre-amyloid deposits. Finally, gene co-expression analysis supports a role for ITM2B/BRI2 in disease-associated microglial responses. These data demonstrate that microglia are major contributors to the production of amyloid forming peptides in FBD, potentially acting as instigators of neurodegeneration. Additionally, these data also suggest ITM2B/BRI2 may be part of a microglial response to disease, motivating further investigations of its role in microglial activation. These data have implications for our understanding of the role of microglia and the innate immune response in the pathogenesis of FBD and other neurodegenerative dementias including Alzheimer’s disease.

Progressive supranuclear palsy (PSP) is a rare Parkinsonian disorder characterized by problems with movement, balance, cognition, and other symptoms. PSP differs from Alzheimer’s disease (AD) and other neurodegenerative diseases displaying abnormal forms of the microtubule-associated protein tau (“tauopathies”) by the presence of pathology not only in neurons, but also in astrocytes and oligodendrocytes. Genetic contributors may mediate these differences, however much of PSP genetics remains unexplained. Here we conducted the largest genome-wide association study (GWAS) of PSP to date including 2,779 cases (2,595 neuropathologically-confirmed) and 5,584 controls and identified six independent PSP susceptibility loci with genome-wide significant ( p < 5×10 -8 ) associations including five known ( MAPT , MOBP , STX6 , RUNX2 , SLCO1A2 ) and one novel locus ( C4A ). Integration with cell type-specific epigenomic annotations revealed a unique oligodendrocytic signature that distinguishes PSP from AD and Parkinson’s disease. Candidate PSP risk gene prioritization using expression quantitative trait loci (eQTLs) identified oligodendrocyte-specific effects on gene expression in half of the genome-wide significant loci, as well as an association with elevated C4A expression in bulk brain tissue which may be driven by increased C4A copy number in PSP cases. Finally, histological studies demonstrated abnormal tau aggregates in oligodendrocytes that colocalize with C4 (complement) deposition. Integrating GWAS with functional studies including epigenomic and eQTL analyses, we identified potential causal roles for variation in MOBP , STX6 , RUNX2 , SLCO1A2 , and C4A in the pathogenesis of PSP.

Average intensities of all light (PDX) and heavy (SILAC) Class I phosphosites p(STY) identified in 16 PDXs with Tyrosine kinase downstream targets highlighted in yellow.

Legend for Supplementary Figures S1-S9.

Average normalized ratio of phosphorylated tyrosine (pY) sites of tyrosine kinases identified in 16 PDXs

Acute lymphoblastic leukaemia (ALL) in infancy, defined as ≤1 year of age at diagnosis, is rare with an incidence of 1.8 cases per 100,000 [1].KMT2A-gene rearrangements are present in up to 80% of infants with ALL and are associated with a poor prognosis.Historically, collaborative group treatment protocols have focused on intensification of conventional chemotherapy, which can include allogeneic haematopoietic stem cell transplant (HSCT) for high-risk infants, however outcomes for KMT2Arearranged infant ALL have remained poor due to high relapse rates and treatment-related mortality [2,3].Given the rarity of the patient population and low survival rates, there is limited data regarding long-term outcomes in survivors of infant ALL in the context of receiving intensive therapy to achieve a cure.We conducted a multi-centre retrospective analysis of all infants diagnosed with ALL in Australia and New Zealand from 1 January 1992 to 31 December 2011 (Human Research Ethics Approval RGS0000001383).Patients were identified from the cancer registry of every paediatric cancer centre in Australia and New Zealand and standardised data were captured for each patient until 28 February 2021, including demographics, disease characteristics, treatment, outcome, a systematic capture of late effects based on the Children's Oncology Group long-term followup guidelines (version 5.0) and date of last follow-up.Event-free survival (EFS) was defined as the time from ALL diagnosis to treatment failure or relapse, all-cause mortality, or second malignancy.Overall survival (OS) was defined as the time from diagnosis to all-cause mortality.Time was censored at the last follow-up if no events were recorded.All analyses were performed using R (version 4.2.2).Over the 20-year period, 119 infants were diagnosed with ALL in Australia and New Zealand.Treatment was administered according to US or European-based infant-specific collaborative group protocols available at the time of diagnosis.Fiveyear OS was 60.5% (SE 4.5) and 5-year EFS was 47.1% (SE 4.7) (Fig. 1; Supplementary Fig. 1).EFS and OS were adversely influenced by the presence of a KMT2A-rearrangement, age <6 months, central nervous system (CNS) involvement, high presenting white blood cell count and CD10-negative immunophenotype, with male sex also an adverse prognostic factor for EFS on univariate analysis (Table 1; Supplementary Fig. 2).Cox regression analysis, with EFS as an endpoint, identified presence of a KMT2A-rearrangement, age <6 months and male

Class I phosphosites (pSTY) identified in T-ALL (ALL-8, ALL-31) and B-ALL (ALL-17, ALL-19)

Phosphotyrosine sites identified by immunoaffinity profiling in ALL PDXs (S1); Comparison of phosphotyrosine enrichment from fresh and frozen PDX (S2); Optimization of quantitative phosphotyrosine profiling of pediatric ALL PDXs (S3); Number of identified Class I phosphosites in each of the PDXs (S4); Unsupervised hierarchical clustering of Class I phosphosites in ALL PDXs segregated based on molecularly-defined subgroups (S5); Comparison of ETP-ALL, Ph-like-ALL, BCP-ALL and T-ALL PDXs by gene expression profiling (S6); Comparison of phosphorylation levels of pTyr sites with gene expression profiling (S7); In vitro sensitivity of ALL PDXs to Sunitinib (S8); Venn diagram showing the number of Light PDX phosphopeptides and Heavy SILAC labelled phosphopeptides identified in each of the 16 PDXs (S9).