Paper Weekly advances

2021

Week 42
Week 43
Week 46 Week 49

2022

Week 01 Week 02

18.10.2021 - 22.10.2021

Selected paper

[1]

Genome-wide analysis of focal DNA hypermethylation in IDH-mutant AML samples
Notes

• IDHm hypermethylation occurs in thousands of focal regions compared to CD34+ and other AML subtypes.
• Not really in CGI
• IDH1m has more hypermethylation than IDH2m
• IDH1 & IDH2 hypermeth highly overlap
• IDHm hypermeth enriched in active enhancer
• MYC & ETV6 but expr not changed
• DNMT3 & TET activity may be concentrated in specific genomic regions

[2]

The implications of IDH mutations for cancer development and therapy
Nodes

• Need heterozygote IDHm/wt
• IDHm -> aberrant histone and DNA methylation, chromatin restructuring, blocking of cellular differentiation and other transformative effects
• Competitive inhibition of TETs
• H2K27me3 changes in glioma
• In hepatoblasts, silencing of HNF4a
• In Pre-adipocytes, downregulation of CEBPa, PPARG, ADIPOQ through H3K27/9me3
• Dysruption of NADPH production
• Dysregulation of GE, DNA repair, inflammation, intracellular trafficking, ageing and cell death
• NAD+ levels is low due to NAPRT1 decreased expression or NAMPT inhibition
• H3K9me3 disrupt DNA damage signalling
• Downregulation of ATM -> impaired DNA damage response
• Increased abundance of unrepaired DNA double-strand breaks link to PARP pathway that need NAD+
• IDHm cells are NAD+ dependant and PARP inhibitor sensitive

[3]

The STAT3-MYC Axis Promotes Survival of Leukemia Stem Cells by Regulating SLC1A5 and Oxidative Phosphorylation
Notes

• STAT3 regulates amino acid influx and glutaminolysis in leukemia stem cells by promoting expression of MYC and SLC1A5. Depletion of glutamine and its downstream metabolites leads to a decrease in OXPHOS activity in LSCs resulting in cell death.

Paper briefly read

• An evaluation of enasidenib for the treatment of acute myeloid leukemia
  Area covered: This review describes the mechanisms of action, the pharmacodynamic and pharmacokinetic properties, the safety, and efficacy of enasidenib. Phase I/II/III clinical trials are also reported and discussed.
  -> To read

• Emerging drug profile: Krebs cycle and cancer: IDH mutations and therapeutic implications
  This review will focus on the underlying biological mechanism and clinical relevance of IDH mutations in cancer.
  -> Not urgent

• Targeting IDH1 and IDH2 Mutations in Acute Myeloid Leukemia: Emerging Options and Pending Questions
  PERSPECTIVE: an update on targeting IDH-mutated AML is provided
  -> Not urgent

• Emerging Roles of Wild-type and Mutant IDH1 in Growth, Metabolism and Therapeutics of Glioma
  Current understanding of the biological roles of wild-type and mutant IDH enzymes in glioblastoma. We discuss the challenges hampering the development of IDH targeted therapeutics and the current status of IDH1 mutant inhibitor development
  -> To read +++

• The impact of mitochondria on cancer treatment resistance available on sci-hub
  REVIEW
  -> To read

• The language of chromatin modification in human cancers
  REVIEW
  -> To read

• The Roles of 2-Hydroxyglutarate
  REVIEW DNAmeth, Histone Methylation, Hypoxia-Inducible Factor Signaling, Other α-Ketoglutarate-Dependent Dioxygenases, Modulates the Immune Microenvironment, Confers Vulnerabilities, Exerts Toxicity on Cancer Cell, Adaption to Hypoxia, Immunometabolite,
  -> To read ++

• Towards a druggable epitranscriptome: Compounds that target RNA modifications in cancer
  REVIEW
  -> Not urgent

• Metabolic reprogramming and epigenetic modifications on the path to cancer
  Review
  -> To read ++

• Deregulation of enhancer structure, function, and dynamics in acute lymphoblastic leukemia
  Review
  -> Not urgent

• Immunotherapeutic Potential of m6A-Modifiers and MicroRNAs in Controlling Acute Myeloid Leukaemia
  Review
  -> To read

• Genome-wide analysis of focal DNA hypermethylation in IDH-mutant AML samples
  BioRxiv “IDHmut-specific hypermethylation was highly enriched for enhancers that form direct interactions with genes involved in normal hematopoiesis and AML, including MYC and ETV6”
  -> To read +++ [DONE]

• Efficacy and Safety Profile of Ivosidenib in the Management of Patients with Acute Myeloid Leukemia (AML): An Update on the Emerging Evidence
  Review
  -> Not urgent

• D-2-Hydroxyglutarate in Glioma Biology
  Review
  -> To read

• A Therapeutic Strategy for Preferential Targeting of TET2-Mutant and TET Dioxygenase–Deficient Cells in Myeloid Neoplasms
  Review -> Not urgent

• R-2-HG in AML… friend or foe?
  COMMENTARY -> To read (short text)

• Cytosolic GDH1 degradation restricts protein synthesis to sustain tumor cell survival following amino acid deprivation
  “depletion of glutamate dehydrogenase 1 (GDH1), an enzyme that converts glutamate to α-ketoglutarate (αKG) confers resistance to amino acid deprivation on kidney renal clear cell carcinoma (KIRC) cells”
  -> To read

• Immature acute leukaemias: lessons from the haematopoietic roadmap
  Review “how modern models of haematopoiesis might inform approaches to diagnosis and management of immature leukaemias”
  -> To read

• Metabolic enzymes function as epigenetic modulators: A Trojan Horse for chromatin regulation and gene expression
  Review “metabolic enzymes functioning as epigenetic modulators in the regulation of chromatin architecture and gene expression”
  -> Not urgent

• RNA modifications in hematopoietic malignancies: a new research frontier

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24.10.2021 - 29.10.2021

Selected paper

[1]

Metabolic reprogramming and epigenetic modifications on the path to cancer
Notes

[2]

Genetic perturbation of PU.1 binding and chromatin looping at neutrophil enhancers associates with autoimmune disease
Notes

[3]

Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C
Notes

[4 but already read]

Rewiring of the Transcription Factor Network in Acute Myeloid Leukemia
Notes

Paper briefly read

• Integrated Stress Response Activity Marks Stem Cells in Normal Hematopoiesis and Leukemia
  AML displayed eIF2 scarcity promoting ATF4 upregulation that activates ISR promoting cell survival.

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15.11.2021 - 19.11.2021

[1]

Non-genetic mechanisms of therapeutic resistance in cancer Notes

[2]

Notes

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13.12.2021 - 17.12.2021

Non_genetic_mechanisms_of_therapeutic_resistance_in_cancer
Notes

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2022

03.01.2022 - 07.01.2022

Focal disruption of DNA methylation

10.01.2022 - 14.01.2022

Universal annotation of the human genome through integration of over a thousand epigenomic datasets