The patient achieved hematological CR on day 163 and remained in molecular CR 3 years after allo-HCT without adverse effects. Quizartinib combined with DLI may be a feasible treatment for early relapse of FLT3-ITD-positive AML after allo-HCT, even with concurrent DNMT3A and NPM1 mutations.

2 months ago

Journal • Post-transplantation

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)

FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • DNMT3A mutation + NPM1 mutation • DNMT3A R882

Vanflyta (quizartinib)

1year

Overexpression of the Signaling Integrator Gab2 Accelerates AML Development in Mice with Dnmt3aR878H and Npm1cA Mutations (ASH 2023)

These data nominate GAB2 overexpression as a factor that may be relevant for the progression of founding clones with DNMT3A and NPM1 mutations to overt AML. Additional studies to define its protein interactome in preleukemic cells, its mechanism of action, and how leukemia-causing mutations in DNMT3A and NPM1 shape the fitness landscape to select for GAB2 overexpression are underway.

1 year ago

Preclinical

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • CD34 (CD34 molecule)

NPM1 mutation • KIT mutation • DNMT3A mutation • PTPN11 mutation • CBL mutation • DNMT3A mutation + NPM1 mutation • FLT3 expression • PAK1 overexpression

over1year

RETAINED FUNCTIONAL NORMAL AND/OR PRE-LEUKEMIC HSCS IN THE BONE MARROW ARE ASSOCIATED TO GOOD PROGNOSIS IN DNMT3A MUT NPM1 MUT AML PATIENTS (EHA 2023)

These data suggest that the presence of normal and/or preleukemic HSCs with multilineage engrafting potential in the bone marrow of naïve patients is associated with good response to standard chemotherapy, providing a basis for the development of novel predictive biomarkers for standard chemotherapy regime. DNMT3A, AML, Leukemic stem cell, Stem cell marker

over 1 year ago

Clinical • IO biomarker

NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • CD38 (CD38 Molecule) • CD34 (CD34 molecule) • ADGRG1 (Adhesion G Protein-Coupled Receptor G1)

NPM1 mutation • DNMT3A mutation • CD34 positive • DNMT3A mutation + NPM1 mutation

2years

Single Cell Genotypic and Phenotypic Analysis of Measurable Residual Disease in Acute Myeloid Leukemia (ASH 2022)

Larger studies are needed to comprehensively elucidate the clonal architecture of MRD and study the dynamics of clonal evolution by comparing clonal architecture and immunophenotype at diagnosis and relapse. Our study paves the road for identifying/eradicating high-risk MRD clones and preventing relapse through a better understanding of the molecular drivers of MRD.

2 years ago

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SRSF2 (Serine and arginine rich splicing factor 2) • WT1 (WT1 Transcription Factor) • CD34 (CD34 molecule)

TP53 mutation • NRAS mutation • IDH2 mutation • NPM1 mutation • DNMT3A mutation • RUNX1 mutation • SRSF2 mutation • DNMT3A mutation + NPM1 mutation

2years

Identification of the Thyrotropin-Releasing Hormone (TRH) as a Novel Biomarker in the Prognosis for Acute Myeloid Leukemia. (PubMed, Biomolecules)

Furthermore, we demonstrated that the expression of TRH in AML could be used to improve the ELN 2017 risk stratification system. In conclusion, our preliminary analysis revealed that TRH, a novel biomarker for AML patients, could be used to evaluate the survival of AML.

2 years ago

Journal

KIT (KIT proto-oncogene, receptor tyrosine kinase) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1)

NPM1 mutation • KIT mutation • DNMT3A mutation • DNMT3A mutation + NPM1 mutation

over2years

TRANSCRIPTIONAL AND TRANSLATIONAL SIGNATURES OF TRIPLE MUTATED DNMT3AKO/FLT3ITD/NPM1C MICE SHOW ALTERED RNAS PROCESSING AND CELL CYCLE PROGRESSION (EHA 2022)

Conclusion The leukemic DNMT3A KO / FLT3 ITD / NPM1 c genotype is characterized by unique transcriptional and translational signatures. The information about deregulated pathways and altered protein synthesis establishes the rational basis for designing new therapeutic approaches in this poor prognosis AML genotype.

over 2 years ago

Preclinical

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • HOXA9 (Homeobox A9) • RAC1 (Rac Family Small GTPase 1)

FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • DNMT3A mutation • DNMT3A mutation + NPM1 mutation • FLT3-ITD expression

over2years

PRECLINICAL AND CLINICAL SIGNS OF RVU120 EFFICACY, A SPECIFIC CDK8/19 INHIBITOR IN DNMT3A MUTATION POSITIVE AML AND HR-MDS (EHA 2022)

Preliminary evidence of clinical response to RVU120 has been also shown in R/R AML and HR-MDS patients positive for DNMT3A mutations. Further molecular studies in greater number of patients under RVU120 treatment are ongoing and will provide evidence for predictive markers of response to RVU120 in AML.

over 2 years ago

Preclinical

NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • CDK9 (Cyclin Dependent Kinase 9)

NPM1 mutation • DNMT3A mutation • DNMT3A mutation + NPM1 mutation

RVU120