These findings support avapritinib as a promising targeted therapy for PDGFRA-altered pediatric gliomas. Further clinical studies are warranted to validate efficacy and resistance mechanisms. 4/4

Avapritinib reduced tumor growth and improved survival in mouse models. In a small compassionate use cohort, partial responses were observed in 3/7 evaluable patients, with good tolerability. 3/n

This study showed that avapritinib, a selective PDGFRA inhibitor, crosses the blood-brain barrier and potently suppresses PDGFRA-driven signaling in preclinical pHGG models with minimal toxicity. 2/n

4. UKALL 2011 confirms strong outcomes: 5-year overall survival of 92% and event-free survival of nearly 84%. Treatment-related mortality is lower than relapse risk

3. Omitting vincristine/dexamethasone pulses during maintenance showed noninferiority for bone marrow relapse, but a slight decrease in event-free survival raises caution

2. High-dose methotrexate during interim maintenance failed to reduce CNS relapse compared to standard Capizzi-style treatment

The source of STAT3/5 activation? Not JAK, mTOR, or PI3K. However, proteasome inhibitor bortezomib blocked the signaling response, suggesting a new angle to target therapy-resistant leukemia cells.

Mass cytometry showed that chemotherapy-treated leukemia cells had increased STAT3/5 phosphorylation after pre-BCR stimulation. This hyperactivation was not seen in untreated cells or wild-type controls.

MYC-high leukemic cells were vulnerable to BRD3/4 inhibition. Combining the MYC inhibitor JQ1 with prednisolone improved treatment response, pointing to a potential therapeutic strategy.

Leukemia cells in the spinal cord/CNS showed a unique expression pattern with upregulation of interleukin and anti-apoptotic pathways, and downregulation of metabolism-related genes. The microenvironment matters.

Single-cell analysis revealed two distinct leukemia cell phenotypes: one was more proliferative and expressed higher MYC and oxidative phosphorylation genes - this subtype became dominant after chemotherapy

Overall, the findings identify a new, subtype-specific interaction between neurons and glioma cells that could have clinical implications, especially regarding the use of GABA-modulating drugs in DMG patients. 5/5

Importantly, lorazepam, a common GABA-enhancing drug, increased tumor growth and shortened survival in these models. This effect was not seen in hemispheric gliomas, where GABAergic input was minimal and non-stimulatory 4/n