Olli Lohi
@lohiolli.bsky.social
Professor of Pediatric Hematology & Oncology at Tampere Univ Hospital and Tampere University, conducting translational research on ALL biology. Tampere, Finland
Pediatric high-grade gliomas (pHGG), including H3K27M-DMGs, remain a major cause of cancer mortality in children. ~15% harbor PDGFRA alterations - making this receptor an attractive therapeutic target 🧵 1/n 👇👇
www.cell.com/cancer-cell/...
www.cell.com/cancer-cell/...
Effective targeting of PDGFRA-altered high-grade glioma with avapritinib
PDGFRA is commonly altered in pediatric HGG. Mayr et al. report that the PDGFRA/KIT
inhibitor avapritinib demonstrates on-target activity, brain penetrance, and survival
benefit in pre-clinical H3K27M...
www.cell.com
April 14, 2025 at 4:45 PM
Pediatric high-grade gliomas (pHGG), including H3K27M-DMGs, remain a major cause of cancer mortality in children. ~15% harbor PDGFRA alterations - making this receptor an attractive therapeutic target 🧵 1/n 👇👇
www.cell.com/cancer-cell/...
www.cell.com/cancer-cell/...
Key findings from UKALL2011: 1. Shortening dexamethasone from 28 to 14 days during induction didn’t reduce toxicity or osteonecrosis in children and young adults with ALL👇👇👇
ascopubs.org/doi/full/10....
ascopubs.org/doi/full/10....
High-Dose Methotrexate in Children and Young Adults With ALL and Lymphoblastic Lymphoma: Results of the Randomized Phase III Study UKALL 2011
PURPOSEUKALL 2011 randomly assigned children and young adults (younger than 25 years) with
ALL or lymphoblastic lymphoma. The aims were to reduce induction toxicity (randomization
1 [R1]), CNS relapse...
ascopubs.org
April 13, 2025 at 5:41 PM
Key findings from UKALL2011: 1. Shortening dexamethasone from 28 to 14 days during induction didn’t reduce toxicity or osteonecrosis in children and young adults with ALL👇👇👇
ascopubs.org/doi/full/10....
ascopubs.org/doi/full/10....
Adding ifosfamide to MAP chemotherapy didn’t improve outcomes for osteosarcoma patients with poor response to initial treatment, and caused more side effects, says JCOG0905 trial.
ascopubs.org/doi/full/10....
ascopubs.org/doi/full/10....
ASCO Publications
ascopubs.org
April 2, 2025 at 5:43 PM
Adding ifosfamide to MAP chemotherapy didn’t improve outcomes for osteosarcoma patients with poor response to initial treatment, and caused more side effects, says JCOG0905 trial.
ascopubs.org/doi/full/10....
ascopubs.org/doi/full/10....
Survivors of childhood cancer face aging-related diseases nearly 18 years earlier than the general population, with a 2.7-fold higher risk by age 65. Early cancer and heart disease prevention should start much sooner in this group 👇👇👇
jamanetwork.com/journals/jam...
jamanetwork.com/journals/jam...
Accelerated Aging in Survivors of Childhood Cancer
This decision analytical model study estimates the lifetime risks of 8 treatment-related cancers and cardiovascular conditions among childhood cancer survivors and compares them with the general popul...
jamanetwork.com
March 30, 2025 at 5:09 PM
Survivors of childhood cancer face aging-related diseases nearly 18 years earlier than the general population, with a 2.7-fold higher risk by age 65. Early cancer and heart disease prevention should start much sooner in this group 👇👇👇
jamanetwork.com/journals/jam...
jamanetwork.com/journals/jam...
Point-of-care CAR T-cell therapy using automated production showed strong results in 10 patients, with lower costs, good safety, and high remission rates—promising for wider access, also in low-resource settings 👇👇
www.cell.com/molecular-th...
www.cell.com/molecular-th...
Safety, Efficacy and Total Cost of Point-of-care Manufactured anti-CD19 CAR T-cell Therapy in India: VELCART trial
Point-of-care manufactured CAR T-cell therapy demonstrates a higher complete remission
rate and presents a promising therapeutic option for low-middle-income countries like
India. The total cost of CA...
www.cell.com
March 30, 2025 at 6:01 AM
Point-of-care CAR T-cell therapy using automated production showed strong results in 10 patients, with lower costs, good safety, and high remission rates—promising for wider access, also in low-resource settings 👇👇
www.cell.com/molecular-th...
www.cell.com/molecular-th...
Targeted therapies like ALK inhibitors and brentuximab vedotin show strong responses in young patients with relapsed ALK+ ALCL, but questions remain about treatment duration and the need for stem cell transplant.
ashpublications.org/bloodadvance...
ashpublications.org/bloodadvance...
Pediatric relapsed/refractory ALK-positive anaplastic large cell lymphoma treatment and outcomes in the targeted-drug era
Key PointsALK inhibitor or brentuximab monotherapy achieve excellent responses in pediatric patients with R/R ALK-positive ALCL.Optimal targeted therapy, d
ashpublications.org
March 28, 2025 at 2:15 PM
Targeted therapies like ALK inhibitors and brentuximab vedotin show strong responses in young patients with relapsed ALK+ ALCL, but questions remain about treatment duration and the need for stem cell transplant.
ashpublications.org/bloodadvance...
ashpublications.org/bloodadvance...
Check out this new study led by Profs Duque-Afonso and Heinaniemi utilizing a mouse model of TCF3-PBX1+ leukemia that mimics human relapse after chemotherapy. About 40% of treated mice survived, with CNS infiltration, similar to clinical setting 👇👇 🧵 1/n
onlinelibrary.wiley.com/doi/10.1002/...
onlinelibrary.wiley.com/doi/10.1002/...
Dynamic evolution of TCF3‐PBX1 leukemias at the single‐cell level under chemotherapy pressure
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. The translocation t(1;19), encoding the TCF3-PBX1 fusion, is associated with intermediate risk and central nervous system (CNS)...
onlinelibrary.wiley.com
March 27, 2025 at 8:22 PM
Check out this new study led by Profs Duque-Afonso and Heinaniemi utilizing a mouse model of TCF3-PBX1+ leukemia that mimics human relapse after chemotherapy. About 40% of treated mice survived, with CNS infiltration, similar to clinical setting 👇👇 🧵 1/n
onlinelibrary.wiley.com/doi/10.1002/...
onlinelibrary.wiley.com/doi/10.1002/...
Multiomics profiling of resistant Ph like ALL cells revealed MYC dependency and a dormant leukemia subpopulation. Dual inhibition of BCL-2 and JAK/STAT or SRC/ABL pathways effectively eradicated these cells, offering a potential therapeutic strategy 👇
ashpublications.org/blood/articl...
ashpublications.org/blood/articl...
Targeting senescent stemlike subpopulations in Philadelphia chromosome–like acute lymphoblastic leukemia
Key PointsOur study discovered new regulators of ruxolitinib response in Ph-like ALL, including c-MYC as a therapeutically targetable codependency.A progno
ashpublications.org
March 27, 2025 at 5:35 PM
Multiomics profiling of resistant Ph like ALL cells revealed MYC dependency and a dormant leukemia subpopulation. Dual inhibition of BCL-2 and JAK/STAT or SRC/ABL pathways effectively eradicated these cells, offering a potential therapeutic strategy 👇
ashpublications.org/blood/articl...
ashpublications.org/blood/articl...
Interesting study using 27 genetically engineered mouse models that closely mimic human hepatocellular carcinoma. 4 subtypes were identified and cladribine, combined with standard therapy, showed promising efficacy for a specific subtype 👇👇
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Human-correlated genetic models identify precision therapy for liver cancer - Nature
As proof of principle, an analysis using a suite of human-aligned immunocompetent mouse models of hepatocellular carcinoma identifies a promising therapeutic candidate, cladribine, which acts in ...
www.nature.com
March 27, 2025 at 5:34 PM
Interesting study using 27 genetically engineered mouse models that closely mimic human hepatocellular carcinoma. 4 subtypes were identified and cladribine, combined with standard therapy, showed promising efficacy for a specific subtype 👇👇
www.nature.com/articles/s41...
www.nature.com/articles/s41...
By age 60, about 60% of the normal oesophageal epithelium is occupied by cell clones with driver mutations. In contrast, this proportion is much lower in the intestines (~1%) and *stomach* (~5%), see new study 👇👇👇
www.nature.com/articles/s41...
www.nature.com/articles/s41...
The somatic mutation landscape of normal gastric epithelium - Nature
Whole-gene sequencing of microdissected gastric glands from individuals with and without gastric cancer reveals distinct patterns of somatic mutations and provides insights into influen...
www.nature.com
March 27, 2025 at 5:33 PM
By age 60, about 60% of the normal oesophageal epithelium is occupied by cell clones with driver mutations. In contrast, this proportion is much lower in the intestines (~1%) and *stomach* (~5%), see new study 👇👇👇
www.nature.com/articles/s41...
www.nature.com/articles/s41...
This article challenges the traditional view that cancer is primarily a "genetic disease", proposing instead that tumorigenesis arises from disruptions in cellular and tissue organization 👇👇👇
journals.plos.org/plosbiology/...
journals.plos.org/plosbiology/...
The end of the genetic paradigm of cancer
Genome sequencing results and single-cell transcriptomics continue to produce findings that challenge the idea that cancer is purely a ‘genetic disease’. This Essay delves into cancer omics data that ...
journals.plos.org
March 27, 2025 at 5:33 PM
This article challenges the traditional view that cancer is primarily a "genetic disease", proposing instead that tumorigenesis arises from disruptions in cellular and tissue organization 👇👇👇
journals.plos.org/plosbiology/...
journals.plos.org/plosbiology/...
Glioblastoma has a dismal prognosis and resists also immunotherapy. Here, a case report with a neoadjuvant dose of triple checkpoint inhibitors before surgery led to strong immune activation and no recurrence after 17 months 👇👇👇
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Neoadjuvant triplet immune checkpoint blockade in newly diagnosed glioblastoma - Nature Medicine
A patient with newly diagnosed glioblastoma was safely treated with neoadjuvant nivolumab, relatlimab and ipilimumab before maximal resection, with comprehensive immune profiling showing the induction...
www.nature.com
March 27, 2025 at 5:32 PM
Glioblastoma has a dismal prognosis and resists also immunotherapy. Here, a case report with a neoadjuvant dose of triple checkpoint inhibitors before surgery led to strong immune activation and no recurrence after 17 months 👇👇👇
www.nature.com/articles/s41...
www.nature.com/articles/s41...
This study reveals a surprising and tumor-specific mechanism by which GABAergic neurons promote the growth of diffuse midline gliomas (DMGs), particularly those with H3K27M mutations 👇👇 🧵🧵 1/n
www.nature.com/articles/s41...
www.nature.com/articles/s41...
GABAergic neuron-to-glioma synapses in diffuse midline gliomas - Nature
Functional, tumour-promoting GABAergic neuron-to-glioma synapses in diffuse midline gliomas are identified.
www.nature.com
March 27, 2025 at 5:31 PM
This study reveals a surprising and tumor-specific mechanism by which GABAergic neurons promote the growth of diffuse midline gliomas (DMGs), particularly those with H3K27M mutations 👇👇 🧵🧵 1/n
www.nature.com/articles/s41...
www.nature.com/articles/s41...
In high-risk neuroblastoma, catecholamine positivity at complete remission (CR) predicted worse event-free (38% vs. 80%) and overall survival (52% vs. 86%). 3-methoxytyramine at CR was a strong prognostic marker for poor OS (HR 7.5, 95% CI 2.0–28.6) 👇
ascopubs.org/doi/10.1200/...
ascopubs.org/doi/10.1200/...
Urinary Catecholamines Predict Relapse During Complete Remission in High-Risk Neuroblastoma | JCO Precision Oncology
PURPOSEUrinary catecholamine metabolites are well-known biomarkers for the diagnosis (Dx)
of neuroblastoma, but their clinical significance in determining therapy response
during treatment is not well...
ascopubs.org
February 26, 2025 at 8:36 PM
In high-risk neuroblastoma, catecholamine positivity at complete remission (CR) predicted worse event-free (38% vs. 80%) and overall survival (52% vs. 86%). 3-methoxytyramine at CR was a strong prognostic marker for poor OS (HR 7.5, 95% CI 2.0–28.6) 👇
ascopubs.org/doi/10.1200/...
ascopubs.org/doi/10.1200/...
Thirty percent of children with Wilms cancer have a predisposition gene mutation. In a cohort of 137 cases, Wilms tumour development was observed to vary by gene and timing of mutation, influencing driver events and clonal architecture 👇👇👇
pmc.ncbi.nlm.nih.gov/articles/PMC...
pmc.ncbi.nlm.nih.gov/articles/PMC...
Predisposition footprints in the somatic genome of Wilms tumours
Ten percent of children with cancer harbour a mutation in a predisposition gene. In children with the kidney cancer, Wilms tumour, the prevalence is as high as 30%. Certain predispositions are associa...
pmc.ncbi.nlm.nih.gov
February 23, 2025 at 9:32 AM
Thirty percent of children with Wilms cancer have a predisposition gene mutation. In a cohort of 137 cases, Wilms tumour development was observed to vary by gene and timing of mutation, influencing driver events and clonal architecture 👇👇👇
pmc.ncbi.nlm.nih.gov/articles/PMC...
pmc.ncbi.nlm.nih.gov/articles/PMC...
Osteosarcoma's evolution driven by chromothripsis, found in 74% of cases, causing genomic instability and tumor heterogeneity. Novel mechanism, LTA chromothripsis, triggers TP53 inactivation and oncogene amplification. Genome-wide LOH predicts prognosis 👇👇👇
www.cell.com/cell/fulltex...
www.cell.com/cell/fulltex...
Ongoing chromothripsis underpins osteosarcoma genome complexity and clonal evolution
Ongoing chromothripsis shapes genomic evolution in a diverse range of sarcomas and
carcinomas. High-grade osteosarcoma is predominantly driven by the mechanism of loss-translocation-amplification
chro...
www.cell.com
January 25, 2025 at 11:51 AM
Osteosarcoma's evolution driven by chromothripsis, found in 74% of cases, causing genomic instability and tumor heterogeneity. Novel mechanism, LTA chromothripsis, triggers TP53 inactivation and oncogene amplification. Genome-wide LOH predicts prognosis 👇👇👇
www.cell.com/cell/fulltex...
www.cell.com/cell/fulltex...
VenEx trial showed that ex vivo drug sensitivity is beneficial for selecting patients with R/R or sAML for venetoclax-azacitidine therapy 👇👇👇
ashpublications.org/blood/articl...
ashpublications.org/blood/articl...
Ex vivo venetoclax sensitivity predicts clinical response in acute myeloid leukemia in the prospective VenEx trial
Key PointsBlast-specific ex vivo venetoclax sensitivity correlated strongly with treatment responses and predicted longer survival.VenEx trial showed that
ashpublications.org
January 25, 2025 at 11:50 AM
VenEx trial showed that ex vivo drug sensitivity is beneficial for selecting patients with R/R or sAML for venetoclax-azacitidine therapy 👇👇👇
ashpublications.org/blood/articl...
ashpublications.org/blood/articl...
ALLO_GD2-CART01, an allogeneic CAR T-cell therapy targeting GD2, showed promise in 5 children with relapsed/refractory high-risk neuroblastoma. Despite cytokine release syndrome and GVHD, 2 complete and 1 partial response were achieved 👇👇👇
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Donor-derived GD2-specific CAR T cells in relapsed or refractory neuroblastoma - Nature Medicine
In a case series of five children with treatment-refractory neuroblastoma, it was feasible to manufacture and administer donor-derived GD2-specific CAR T cells and clinical responses were seen in four...
www.nature.com
January 25, 2025 at 11:49 AM
ALLO_GD2-CART01, an allogeneic CAR T-cell therapy targeting GD2, showed promise in 5 children with relapsed/refractory high-risk neuroblastoma. Despite cytokine release syndrome and GVHD, 2 complete and 1 partial response were achieved 👇👇👇
www.nature.com/articles/s41...
www.nature.com/articles/s41...
CD5-targeting CAR-T therapy achieved 100% remission by day 30 in a study of 19 r/r T-ALL patients, including those who failed CD7 CAR-T. Late infections and relapse remain challenges. Transplantation may improve long-term outcomes 👇👇👇
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Allogeneic CD5-specific CAR-T therapy for relapsed/refractory T-ALL: a phase 1 trial - Nature Medicine
In a phase 1 trial, pediatric or adult patients with T-ALL who received CD5-targeted CAR-T cell therapy using cells from previous or newly matched donors showed an encouraging clinical response rate, ...
www.nature.com
January 25, 2025 at 11:48 AM
CD5-targeting CAR-T therapy achieved 100% remission by day 30 in a study of 19 r/r T-ALL patients, including those who failed CD7 CAR-T. Late infections and relapse remain challenges. Transplantation may improve long-term outcomes 👇👇👇
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Reposted by Olli Lohi
I'm delighted to announce that the Pharma Proteomics Project will commence full-scale proteomic profiling of the UK Biobank in 2025. We have selected the Olink Proteomics Explore HT platform and Ultima Genomics UG 100 sequencers for this unprecedented study.
www.ukbiobank.ac.uk/learn-more-a...
www.ukbiobank.ac.uk/learn-more-a...
Launch of world’s most significant protein study set to usher in new understanding for medicine
www.ukbiobank.ac.uk
January 10, 2025 at 8:18 AM
I'm delighted to announce that the Pharma Proteomics Project will commence full-scale proteomic profiling of the UK Biobank in 2025. We have selected the Olink Proteomics Explore HT platform and Ultima Genomics UG 100 sequencers for this unprecedented study.
www.ukbiobank.ac.uk/learn-more-a...
www.ukbiobank.ac.uk/learn-more-a...
Children with ETV6::RUNX1 or high-hyperdiploid B-ALL have excellent 5-year EFS (97.7% and 94.7%) with low-intensity therapy. However, high-hyperdiploid B-ALL with slow MRD response needs improved treatments 👇👇👇
ashpublications.org/blood/articl...
ashpublications.org/blood/articl...
Outcomes in patients with ETV6::RUNX1 or high-hyperdiploid B-ALL treated in the St. Jude Total Therapy XV/XVI studies
Key PointsAmong NCI high-risk patients, 93% with ETV6::RUNX1 and 54% with hyperdiploid B-ALL had excellent outcomes with low-intensity therapy.NCI high-ris
ashpublications.org
January 9, 2025 at 8:27 PM
Children with ETV6::RUNX1 or high-hyperdiploid B-ALL have excellent 5-year EFS (97.7% and 94.7%) with low-intensity therapy. However, high-hyperdiploid B-ALL with slow MRD response needs improved treatments 👇👇👇
ashpublications.org/blood/articl...
ashpublications.org/blood/articl...
Reposted by Olli Lohi
I was walking along a trail yesterday and noticed this Madagascar periwinkle (Catharanthus roseus) - the plant that “vinca alkaloid” anti-cancer drugs vincristine and vinblastine were isolated from back in 1961. They’re still used today, especially vincristine for acute lymphoid leukemia and NHL.
January 8, 2025 at 9:32 PM
I was walking along a trail yesterday and noticed this Madagascar periwinkle (Catharanthus roseus) - the plant that “vinca alkaloid” anti-cancer drugs vincristine and vinblastine were isolated from back in 1961. They’re still used today, especially vincristine for acute lymphoid leukemia and NHL.
A phase 1 trial of B7-H3 CAR T cells for #DIPG showed tolerability with repetitive intracerebroventricular dosing and a median survival of 10.7 months post-infusion. Three patients survived over 3 years, supporting further phase 2 investigation 👇👇👇
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial - Nature Medicine
In the final report of a phase 1 trial evaluating intracerebroventricular B7-H3-targeting CAR T cells in children and young adults with diffuse intrinsic pontine glioma, repeated intracranial infusion...
www.nature.com
January 9, 2025 at 4:10 PM
A phase 1 trial of B7-H3 CAR T cells for #DIPG showed tolerability with repetitive intracerebroventricular dosing and a median survival of 10.7 months post-infusion. Three patients survived over 3 years, supporting further phase 2 investigation 👇👇👇
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Novel GET model accurately predicts gene #expression across 213 cell types using chromatin accessibility data as input, uncovering regulatory networks and interactions. It identifies novel regulatory regions and disease-relevant mutations 👇👇👇
www.nature.com/articles/s41...
www.nature.com/articles/s41...
A foundation model of transcription across human cell types - Nature
A foundation model learns transcriptional regulatory syntax from chromatin accessibility and sequence data across a range of cell types to predict gene expression and transcription factor interactions...
www.nature.com
January 9, 2025 at 4:09 PM
Novel GET model accurately predicts gene #expression across 213 cell types using chromatin accessibility data as input, uncovering regulatory networks and interactions. It identifies novel regulatory regions and disease-relevant mutations 👇👇👇
www.nature.com/articles/s41...
www.nature.com/articles/s41...