News - MGA mutation - LARVOL VERI

10ms

Functional characterization of cooperating MGA mutations in RUNX1::RUNX1T1 acute myeloid leukemia. (PubMed, Leukemia)

RUNX1::RUNX1T1 expression in Mga-deficient murine hematopoietic cells leads to a more aggressive AML with a significantly shortened latency. These data show that MGA regulates multiple pro-proliferative pathways in hematopoietic cells and cooperates with the RUNX1::RUNX1T1 fusion oncoprotein to enhance leukemogenesis.

10 months ago

Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • RUNX1 (RUNX Family Transcription Factor 1) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • MGA (MAX Dimerization Protein MGA)

RUNX1 mutation • RUNX1-RUNX1T1 fusion • MGA mutation

1year

Whole Genome and Transcriptome Sequencing of 21 Paired Chronic and Blast Phase CML Cases: Acquisition of Genomic Alterations, Changes in the Transcriptomic Profiles and Occurrence of B-Cell Receptor Rearrangements (ASH 2023)

1) Extensive genetic profiling indicated a substantial clonal evolution in the progression from CP to BP CML including loss of ASXL1 mutations, expansion of RUNX1 mutated clones, multiple CNA, and the frequent acquisition of a BCR rearrangement in BP with a transcriptomic phenotype resembling B-ALL. 2) A subset of CML cases in CP already showed a transcriptomic phenotype resembling acute leukemia indicating a rapid progression to BP. 3) The presence of a RUNX1 mutated subclone or a clonal BCR rearrangement seem to represent a warning signal in CML CP.

1 year ago

Clinical

ABL1 (ABL proto-oncogene 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • WT1 (WT1 Transcription Factor) • BCOR (BCL6 Corepressor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • MECOM (MDS1 And EVI1 Complex Locus) • MGA (MAX Dimerization Protein MGA) • MLLT3 (MLLT3 Super Elongation Complex Subunit)

DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • CDKN2A deletion • TET2 mutation • MLL rearrangement • BCOR mutation • IKZF1 deletion • WT1 mutation • MECOM rearrangement • SETD2 mutation • ABL1 fusion • MGA mutation • MLL3 mutation

over1year

Mucous Gland Adenoma of the Lung: A Neoplastic Counterpart of Mucinous Bronchial Glands. (PubMed, Mod Pathol)

In conclusion, the gene expression profile, taken together with the histological similarity between MGA and bronchial glands, and the preferred location of the tumors (proximal airways with submucosal glands) suggest that MGA is a neoplastic counterpart of mucinous bronchial glands. NKX3.1 immunohistochemistry can be a sensitive and specific ancillary marker that distinguishes MGA from other histologic mimics.

over 1 year ago

Journal

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • MGA (MAX Dimerization Protein MGA) • NKX3-1 (NK3 homeobox 1)

BRAF V600E • KRAS mutation • BRAF V600 • AKT1 mutation • MGA mutation

over1year

Mutational Spectrum and Prognosis Analysis of Young Patients with Diffuse Large B-Cell Lymphoma Based on Next-Generation Sequencing (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)

The aaIPI staging combination with molecular biology markers is more conducive to accurately judging the prognosis of young DLBCL patients. TP53, POU2AF1 and CCND3 mutations predict worse survival in the patients with the aaIPI high-risk group.

over 1 year ago

Retrospective data • Journal • Next-generation sequencing

TP53 (Tumor protein P53) • B2M (Beta-2-microglobulin) • CARD11 (Caspase Recruitment Domain Family Member 11) • CCND3 (Cyclin D3) • MGA (MAX Dimerization Protein MGA) • POU2AF1 (POU Class 2 Homeobox Associating Factor 1)

CARD11 mutation • MGA mutation • SPEN mutation

almost2years

In vivo modeling of CLL transformation to Richter's syndrome reveals convergent evolutionary paths and therapeutic vulnerabilities. (PubMed, Blood Cancer Discov)

Comparative human and murine RS analyses demonstrated tonic PI3K signaling as a key feature of transformed disease, with constitutive activation of the AKT and S6 kinases, down-modulation of the receptor phosphatase PTEN, and convergent activation of MYC/PI3K transcriptional programs underlying enhanced sensitivity to MYC/mTOR/PI3K inhibition. This robust experimental system presents a unique framework to study lymphoid biology and therapy.

almost 2 years ago

Preclinical • Journal

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • MGA (MAX Dimerization Protein MGA) • CHD2 (Chromodomain Helicase DNA Binding Protein 2)

TP53 mutation • MGA mutation

2years

Disrupting MGA-MYC Driven Metabolic Reprogramming in Richter's Syndrome Pre-Clinical Models Via Novel Therapeutic Approaches (ASH 2022)

In summary, our murine model reveals that MGA/MYC/NME1 axis drives RS through increased mitochondrial OXPHOS and ROS accumulation. Moreover, targeting this axis provides therapeutic benefits for RS, highlighting this pathway as a novel potential target for RS treatment.

2 years ago

Preclinical

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CD5 (CD5 Molecule) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1) • MGA (MAX Dimerization Protein MGA)

MYC overexpression • SF3B1 mutation • MYC expression • MGA mutation

2years

Rapid Generation of Murine CLL/Richter Syndrome Models By Multiplexed CRISPR/Cas9 Editing of Common CLL Driver Genes (ASH 2022)

The effects of the introduced genetic lesions on leukemia cell growth and treatment resistance were investigated by analyzing the mutant allele frequency (MAF) of the injected cells and cells recovered from the spleens of untreated or venetoclax-treated mice... This study shows that multiplex CRISPR/Cas9 editing can be used to rapidly generate murine leukemias with the genetic make-up of human CLL or Richter Syndrome. These models can represent an important preclinical tool to study how individual genetic lesions cooperate during CLL development and progression and how they affect the response to treatment with novel therapeutic agents.

2 years ago

Preclinical

TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • NOTCH1 (Notch 1) • CD19 (CD19 Molecule) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • BIRC3 (Baculoviral IAP repeat containing 3) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • CD5 (CD5 Molecule) • MGA (MAX Dimerization Protein MGA) • POT1 (Protection of telomeres 1) • NFKBIE (NFKB Inhibitor Epsilon) • CHD2 (Chromodomain Helicase DNA Binding Protein 2)

TP53 mutation • ATM mutation • NOTCH1 mutation • Chr del(13)(q14) • MGA mutation

Venclexta (venetoclax)

almost3years

MGA mutation status affect tumor immunomicroenvironment and predict the effect of immune check point inhibitor: From NSCLC to pan-cancers analysis (AACR 2022)

This research investigated the immunotherapeutic value of MGA in pan-cancers, indicating that MGA-MUT could serve as a potential predictive biomarker for immune checkpoint inhibitors, and providing preliminary evidence regarding the function of MGA mutation and its role in anti-tumor immunity.

almost 3 years ago

Tumor Mutational Burden • IO biomarker • Pan tumor

TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • MGA (MAX Dimerization Protein MGA)

MGA mutation

3years

Predictive Value of Max's Giant Associated Protein Mutation in Outcomes of Lung Adenocarcinoma Patients Treated With Immune Checkpoint Inhibitors. (PubMed, Front Cell Dev Biol)

In conclusion, our results demonstrated that MGA mutation was an independent predictive biomarker for ICI therapy. These results may provide a novel insight into identifying potential patients with LUAD for ICI therapy.

3 years ago

Clinical • Journal • Checkpoint inhibition • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MGA (MAX Dimerization Protein MGA)

PD-L1 expression • TMB-L • MGA mutation