News - RUNX1 mutation

14d

Phase I First-in-Human Dose Escalation Study of the oral Casein Kinase 1α and Cyclin Dependent Kinase 7/9 inhibitor BTX-A51 in advanced MDS and AML. (PubMed, Res Sq)

Ex-vivo studies confirmed higher efficacy of BTX-A51 on RUNX1 -mutated myeloblasts and demonstrate synergy with azacitidine and venetoclax. Although the overall efficacy was modest, this study lays the groundwork for future studies with improved patient selection and combination approaches.

14 days ago

P1 data • Journal • Metastases

RUNX1 (RUNX Family Transcription Factor 1) • CDK7 (Cyclin Dependent Kinase 7)

RUNX1 mutation • MCL1 expression • TP53 expression

Venclexta (venetoclax) • azacitidine • BTX-A51

23d

A phase 1 study of the amino acid modulator pegcrisantaspase and venetoclax for relapsed/refractory acute myeloid leukemia. (PubMed, Blood)

Response correlated with alterations in proteins involved in mRNA translation. In patients with RUNX1 mutations, the composite complete rate was 100%.

23 days ago

P1 data • Journal • IO biomarker

RUNX1 (RUNX Family Transcription Factor 1)

RUNX1 mutation

Venclexta (venetoclax) • Asparec (PEGylated recombinant Erwinia chrysantemi-derived L-asparaginase)

Data-driven, harmonised classification system for myelodysplastic syndromes: a consensus paper from the International Consortium for Myelodysplastic Syndromes. (PubMed, Lancet Haematol)

After the survey, myelodysplastic syndromes with low blasts (ie, less than 5%) and myelodysplastic syndromes with increased blasts (ie, 5% or more) were recognised as disease entities. Our data-driven approach can efficiently harmonise current classifications of myelodysplastic syndromes and provide a reference for patient management in a real-world setting.

1 month ago

Review • Journal

TP53 (Tumor protein P53) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1)

TP53 mutation • RUNX1 mutation • Chr del(5q) • Chr del(7q)

The importance of genetic variant cleaners: From patient to wet lab and back to clinical practice. (PubMed, Br J Haematol)

Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19776.

1 month ago

Journal

RUNX1 (RUNX Family Transcription Factor 1)

RUNX1 mutation

2ms

Genomic Landscape of Myelodysplastic/Myeloproliferative Neoplasms: A Multi-Central Study. (PubMed, Int J Mol Sci)

In MDS/MPN-U, CBL mutations (p < 0.05) were the sole negative prognostic factors identified in our study by multivariate analysis (p < 0.05). Overall, our study provides genetic insights into various MDS/MPN subtypes, which may aid in diagnosis and clinical decision-making for patients with MDS/MPN.

2 months ago

Journal

TP53 (Tumor protein P53) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • SETBP1 (SET Binding Protein 1)

TP53 mutation • RUNX1 mutation • ASXL1 mutation • CBL mutation • SRSF2 mutation

2ms

Omacetaxine and Venetoclax for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Harboring Mutant RUNX1 (clinicaltrials.gov)

P1/2, N=24, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Aug 2025 --> Sep 2024 | Trial primary completion date: Aug 2025 --> Sep 2024

2 months ago

Trial completion • Trial completion date • Trial primary completion date

RUNX1 (RUNX Family Transcription Factor 1)

RUNX1 mutation

Venclexta (venetoclax) • Synribo (omacetaxine mepesuccinate)

2ms

Prognostic impact of DTA mutation and co-occurring mutations in patients with myelodysplastic syndrome. (PubMed, Mol Biol Rep)

DTA mutations are frequently observed in patients with MDS, often accompanied by genes involved in RNA splicing and transcription factors like SF3B1 and RUNX1. DTA and concomitant mutations affect prognosis in MDS patients and RUNX1 was identified as an independent poor prognostic factor in patients with DTA mutations.

2 months ago

Retrospective data • Journal

TP53 (Tumor protein P53) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • SETBP1 (SET Binding Protein 1)

TP53 mutation • DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • TET2 mutation • SF3B1 mutation • U2AF1 mutation

2ms

Outcomes with single-agent gilteritinib for relapsed or refractory FLT3-mutant AML after contemporary induction therapy. (PubMed, Blood Adv)

Gilteritinib is the current standard of care for relapsed or refractory FLT3-mutated AML in many countries, however outcomes for patients relapsing after contemporary first-line therapies (intensive chemotherapy with midostaurin, or non-intensive chemotherapy with venetoclax) are uncertain. Twenty patients received gilteritinib as first salvage having progressed following first-line therapy with venetoclax, with CR/CRi achieved in 25% and median survival 4.5 months. Real-world results with gilteritinib mirror those seen in the clinical trials but outcomes remain suboptimal, with more effective strategies needed.

2 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A)

FLT3 mutation • RUNX1 mutation • KMT2A rearrangement • MLL rearrangement

Venclexta (venetoclax) • Xospata (gilteritinib) • Rydapt (midostaurin)

2ms

Molecular precision medicine: Multi-omics-based stratification model for acute myeloid leukemia. (PubMed, Heliyon)

CS1 showed good sensitivity to cytarabine, while CS2 was sensitive to RXR agonists...With advancements in sequencing technology and machine learning algorithms, AML is poised to transition towards multi-omics precision medicine in the future. We aspire for our study to offer new perspectives on multi-drug combination clinical trials and multi-targeted precision medicine for AML.

2 months ago

Journal • IO biomarker

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • WT1 (WT1 Transcription Factor)

TP53 mutation • FLT3 mutation • NPM1 mutation • KIT mutation • DNMT3A mutation • RUNX1 mutation • WT1 mutation

cytarabine

6ms

Omacetaxine and Venetoclax for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Harboring Mutant RUNX1 (clinicaltrials.gov)

P1/2, N=24, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=84 --> 24

6 months ago

Enrollment closed • Enrollment change

RUNX1 (RUNX Family Transcription Factor 1)

RUNX1 mutation

Venclexta (venetoclax) • Synribo (omacetaxine mepesuccinate)

6ms

Comprehensive insights into AML relapse: genetic mutations, clonal evolution, and clinical outcomes. (PubMed, Cancer Cell Int)

Our study integrates karyotype, gene rearrangements, and gene mutation results to provide a further understanding of AML heterogeneity and evolution. We demonstrate the clinical relevance of specific mutations and clonal evolution patterns, emphasizing the need for personalized therapies and measurable residual disease monitoring in AML management. By bridging the gap between genetics and clinical outcome, we move closer to tailored AML therapies and improved patient prognoses.

6 months ago

Clinical data • Journal

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • WT1 (WT1 Transcription Factor)

FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • RUNX1 mutation • WT1 mutation

6ms

CLONAL EVOLUTION IN SECUNDARY ACUTE MYELOID LEUKEMIA ARISING FROM MYELOPROLIFERATIVE NEOPLASMS (EHA 2024)

Our data suggest that secondary AML arising from MPNs is a genetically distinct entity compared to de novoAML, with a higher incidence of mutations in high-risk genes such as TP53, a high rate of relapse/refractorinessand poor prognosis with current therapeutic strategies. NGS determination of somatic mutations could identifyhigh-risk-progression patients, and monitoring these mutations could be useful, along with other clinical data,to anticipate progression.

6 months ago

TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CALR (Calreticulin)

TP53 mutation • RUNX1 mutation • SRSF2 mutation • U2AF1 mutation • JAK2 V617F • CALR mutation

Oncomine Myeloid Research Assay

7ms

Latest Findings on the Role of RUNX1 in Bone Development and Disorders (PubMed, Sichuan Da Xue Xue Bao Yi Xue Ban)

However, the roles of RUNX1 in regulating the hypertrophic differentiation of chondrocytes, the sexual dimorphism of activities of osteoclasts, as well as bone loss in diabetes mellitus, senescence, infection, chronic inflammation, etc, are still not fully understood. This review provides a systematic summary of the research progress concerning RUNX1 in the field of bone biology, offering new ideas for using RUNX1 as a potential target for bone related diseases, especially osteoarthritis, delayed fracture healing, and osteoporosis.

7 months ago

Journal

RUNX1 (RUNX Family Transcription Factor 1)

RUNX1 mutation

7ms

Erythroid predominance in bone marrow biopsies of AML patients after decitabine treatment correlates with mutation profile and complete remission. (PubMed, Pathobiology)

We conclude that early histological bone marrow examination for the development of an EDR may be helpful to predict response in AML patients during treatment with DAC.

7 months ago

Journal • Biopsy

RUNX1 (RUNX Family Transcription Factor 1) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)

RUNX1 mutation • U2AF1 mutation

decitabine

7ms

Pemigatinib After Chemotherapy for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov)

P1, N=32, Recruiting, OHSU Knight Cancer Institute | Trial completion date: Aug 2024 --> Feb 2026 | Trial primary completion date: Feb 2024 --> Aug 2025

7 months ago

Trial completion date • Trial primary completion date

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • MECOM (MDS1 And EVI1 Complex Locus) • NUP214 (Nucleoporin 214) • GATA2 (GATA Binding Protein 2) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • DEK (DEK Proto-Oncogene) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

TP53 mutation • FLT3 mutation • RUNX1 mutation • ASXL1 mutation • EZH2 mutation • MLL rearrangement • SRSF2 mutation • U2AF1 mutation • BCOR mutation • Chr del(5q) • STAG2 mutation • FLT3 wild-type • Chr t(9;11) • ZRSR2 mutation

cytarabine • Pemazyre (pemigatinib) • daunorubicin • Starasid (cytarabine ocfosfate)

8ms

Differential prognostic values of the three AKT isoforms in acute myeloid leukemia. (PubMed, Sci Rep)

Curiously, although modestly varying among AML samples, a high AKT1 expression shows in contrast as a strong predictor of a better patient outcome. These data suggest that AKT3 and AKT1 expressions have strong, yet opposite, prognostic values.

8 months ago

Journal

NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • AKT3 (V-akt murine thymoma viral oncogene homolog 3)

NPM1 mutation • RUNX1 mutation • ASXL1 mutation • SF3B1 mutation • SRSF2 mutation • U2AF1 mutation • BCOR mutation • AKT2 expression • AKT3 expression

8ms

Natural history of clonal haematopoiesis seen in real-world haematology settings. (PubMed, Br J Haematol)

The mean variant allele frequency across all genes was higher in progressors than in non-progressors (36.9% ± 4.62% vs. 24.1% ± 1.67%, p = 0.0064). This analysis in the post-CHRS era underscores the natural history of CH, providing insight into patterns of progression to MN.

8 months ago

Journal • Real-world evidence • Real-world

DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2)

DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • TET2 mutation

8ms

Clinical analysis of allogeneic hematopoietic stem cell transplantation for seven cases of acute myeloid leukemia with BCR::ABL1 fusion (PubMed, Zhonghua Xue Ye Xue Za Zhi)

In addition, allo-HSCT could enhance the molecular response rate. Maintenance therapy post-HSCT with TKI could improve prognosis.

8 months ago

Journal

ABL1 (ABL proto-oncogene 1) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • PHF6 (PHD Finger Protein 6)

NPM1 mutation • RUNX1 mutation • ASXL1 mutation • PHF6 mutation • ABL1 fusion

8ms

Hematopoietic stem cells with granulo-monocytic differentiation state overcome venetoclax sensitivity in patients with myelodysplastic syndromes. (PubMed, Nat Commun)

While MDS HSCs in an undifferentiated cellular state are sensitive to venetoclax treatment, differentiation towards a granulo-monocytic-biased transcriptional state, through the acquisition or expansion of clones with STAG2 or RUNX1 mutations, affects HSCs' survival dependence from BCL2-mediated anti-apoptotic pathways to TNFα-induced pro-survival NF-κB signaling and drives resistance to venetoclax-mediated cytotoxicity. Our findings reveal how hematopoietic stem and progenitor cell (HSPC) can eventually overcome therapy-induced depletion and underscore the importance of using close molecular monitoring to prevent HSPC hierarchical change in MDS patients enrolled in clinical trials of venetoclax.

8 months ago

Journal • IO biomarker

BCL2 (B-cell CLL/lymphoma 2) • RUNX1 (RUNX Family Transcription Factor 1) • TNFA (Tumor Necrosis Factor-Alpha) • STAG2 (Stromal Antigen 2)

RUNX1 mutation • STAG2 mutation

Venclexta (venetoclax)

8ms

RUNX1 C-terminal Mutations Impair Blood Cell Differentiation by Perturbing Specific Enhancer-Promoter Networks. (PubMed, Blood Adv)

Additionally, we uncovered enrichment of RUNX1R320* and FOXK2 binding at the MYC super enhancer locus, significantly upregulating MYC transcription and signaling pathways. Together, our study demonstrates that most RUNX1 mutations outside the DNA binding domain are not subject to nonsense mediated decay, producing protein products that act in concert with additional cofactors to dysregulate hematopoiesis through mechanisms distinct from that induced by RUNX1 depletion.

8 months ago

Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • RUNX1 (RUNX Family Transcription Factor 1)

RUNX1 mutation

8ms

Investigations of the prognostic value of RUNX1 mutation in acute myeloid leukemia patients: Data from a real-world study. (PubMed, Leuk Res)

In those who received venetoclax plus hypomethylating agents, RUNX1mut was not predictive of CRc and comparable OS and EFS were seen between intermediate-risk and adverse-risk groups...Its prognostic value depended more on treatment and co-occurrent abnormalities. VEN-HMA may abrogate the prognostic impact of RUNX1, which merits a larger prospective cohort to illustrate.

8 months ago

Journal • Real-world evidence • Real-world

RUNX1 (RUNX Family Transcription Factor 1)

RUNX1 mutation

Venclexta (venetoclax)

8ms

Aggressive systemic mastocytosis with the co-occurrence of PRKG2::PDGFRB, KAT6A::NCOA2, and RXRA::NOTCH1 fusion transcripts and a heterozygous RUNX1 frameshift mutation. (PubMed, Cancer Genet)

The patient rapidly evolved towards SM-AHN, characterized by the persistence of the PRKG2::PDGFRB chimera, due to the presence of an extra copy of the der(5)t(4;5)(q24;q34) chromosome and an increase in the RUNX1 mutation allelic frequency. The results indicated that the transcriptional landscape and the mutational profile of SM deserve attention to predict the evolution and prognosis of this complex disease, whose classification criteria are still a matter of debate.

8 months ago

Journal

KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NOTCH1 (Notch 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • KAT6A (Lysine Acetyltransferase 6A) • NCOA2 (Nuclear Receptor Coactivator 2)

RUNX1 mutation • KIT D816V • JAK2 V617F

8ms

Donor Stem Cell Transplantation Using α/β+ T-lymphocyte Depleted Grafts From HLA Mismatched Donors (clinicaltrials.gov)

P2, N=9, Terminated, Memorial Sloan Kettering Cancer Center | Trial completion date: Jul 2024 --> Mar 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jul 2024 --> Mar 2024; Low accrual

8 months ago

Trial completion date • Trial termination • Trial primary completion date

TP53 (Tumor protein P53) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • CRLF2 (Cytokine Receptor Like Factor 2) • IKZF1 (IKAROS Family Zinc Finger 1) • NUP214 (Nucleoporin 214) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • DEK (DEK Proto-Oncogene)

TP53 mutation • RUNX1 mutation • KMT2A rearrangement • IKZF1 mutation • MLL mutation • Chr t(9;11)

Rituxan (rituximab) • cyclophosphamide • clofarabine • melphalan • fludarabine IV • thiotepa • busulfan

8ms

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.

8 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

9ms

Molecular and clinical analyses of PHF6 mutant myeloid neoplasia provide their pathogenesis and therapeutic targeting. (PubMed, Nat Commun)

Finally, we demonstrate a negative prognostic role of PHF6MT, especially in association with RUNX1. The negative effects on survival are additive as PHF6MT cases with RUNX1 mutations have worse outcomes when compared to cases carrying single mutation or wild-type.

9 months ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • PHF6 (PHD Finger Protein 6)

RUNX1 mutation • ASXL1 mutation • U2AF1 mutation • PHF6 mutation

9ms

Comparing Cytarabine + Daunorubicin Therapy Versus Cytarabine + Daunorubicin + Venetoclax Versus Venetoclax + Azacitidine in Younger Patients With Intermediate Risk AML (A MyeloMATCH Treatment Trial) (clinicaltrials.gov)

P2, N=153, Not yet recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025

9 months ago

Trial completion date • Trial primary completion date

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • RARA (Retinoic Acid Receptor Alpha) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • PML (Promyelocytic Leukemia) • CEBPA (CCAAT Enhancer Binding Protein Alpha)

TP53 mutation • FLT3-ITD mutation • NPM1 mutation • RUNX1 mutation • ASXL1 mutation • FLT3-TKD mutation • CEBPA mutation

Venclexta (venetoclax) • cytarabine • azacitidine • daunorubicin • Starasid (cytarabine ocfosfate)

9ms

Clinical characteristics and prognosis of acute myeloid leukemia patients with Runt-related transcription factor 1 mutation: A single-center retrospective analysis. (PubMed, Hematol Oncol)

EZH2 co-mutation, DNMT3A co-mutation, old age and high WBC count were associated with inferior survival of AML-RUNX1mut . Allo-HSCT can significantly improve the prognosis of AML-RUNX1mut .

9 months ago

Retrospective data • Journal

NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • RAS (Rat Sarcoma Virus) • BCORL1 (BCL6 Corepressor Like 1)

NPM1 mutation • DNMT3A mutation • RUNX1 mutation • EZH2 mutation

9ms

Recurrent Wnt Pathway and ARID1A Alterations in Sinonasal Olfactory Carcinoma. (PubMed, Mod Pathol)

A small subset of neuroepithelial tumors might better fit into the superseding molecular category of IDH2-mutant sinonasal carcinoma. At this point, sinonasal neuroendocrine and neuroepithelial tumors may best be regarded as a histologic and molecular spectrum that includes core groups of ONB, olfactory carcinoma, neuroendocrine carcinoma, and IDH2-mutant sinonasal carcinoma.

9 months ago

Journal

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • RUNX1 (RUNX Family Transcription Factor 1) • TP63 (Tumor protein 63) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)

IDH2 mutation • ARID1A mutation • RUNX1 mutation

9ms

Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM). (PubMed, Blood Cancer J)

GMR-AML1 and PD FPD-MM cells were sensitive to homoharringtonine (HHT or omacetaxine) or mebendazole-induced lethality, associated with repression of c-Myc, EVI1, PLK1, CDK6 and MCL1. In luciferase-expressing GMR-AML1 xenograft model, MB, omacetaxine or volasertib monotherapy, or co-treatment with MB and volasertib, significantly reduced AML burden and improved survival in the immune-depleted mice. These findings highlight the molecular features of FPD-MM progression and demonstrate HHT, MB and/or volasertib as effective agents against cellular models of FPD-MM.

9 months ago

Journal • IO biomarker

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • RUNX1 (RUNX Family Transcription Factor 1) • MCL1 (Myeloid cell leukemia 1) • CDK6 (Cyclin-dependent kinase 6) • MECOM (MDS1 And EVI1 Complex Locus)

RUNX1 mutation • BCL2 expression • MYC expression

volasertib (NBL-001) • Synribo (omacetaxine mepesuccinate) • mebendazole

9ms

Advances towards genome-based acute myeloid leukemia classification: A comparative analysis of WHO-HAEM4R, WHO-HAEM5, and International Consensus Classification. (PubMed, Am J Hematol)

However, their clinical implementation heavily relies on comprehensive and sophisticated genomic analysis, including genome and transcriptome levels, alongside the assessment of pathogenetic somatic and germline variations. Discrepancies between WHO-HAEM5 and ICC, such as the assignment of RUNX1 mutations, the rationality of designating AML with mutated TP53 as a unique entity, and the scope of rare genetic fusions, along with the priority of concurrent AML-defining genetic abnormalities, are still pending questions requiring further research for more elucidated insights.

9 months ago

Journal

TP53 (Tumor protein P53) • RUNX1 (RUNX Family Transcription Factor 1)

TP53 mutation • RUNX1 mutation

10ms

Genetic landscape and clinical outcomes of patients with BCOR mutated myeloid neoplasms. (PubMed, Haematologica)

However, RUNX1 co-mutation was associated with an increased risk of post-alloSCT relapse (HR 88.0, P = 0.02), whereas melphalan-based conditioning was associated with a decreased relapse-risk (HR 0.02, P = 0.01). We conclude that mBCOR is a high-risk feature across MDS/AML and that alloSCT improves survival in this population.

10 months ago

Clinical data • Journal

TP53 (Tumor protein P53) • RUNX1 (RUNX Family Transcription Factor 1) • BCL6 (B-cell CLL/lymphoma 6) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)

TP53 mutation • RUNX1 mutation • U2AF1 mutation • BCOR mutation

melphalan

10ms

Real-World Analysis of Clinical Outcomes in AML, Myelodysplasia-Related: a Comparison of ICC and WHO-HAEM5 Criteria. (PubMed, Blood Adv)

AML-MR defined by gene mutations or cytogenetic abnormalities showed similar outcomes regardless of the order of assignment (HR: 0.92, p = .73). We propose to harmonize the two classifications by excluding TP53 mutations from WHO-HAEM5 defined AML-MR group and combining AML-MR defined by gene mutations and cytogenetics to form a unified group.

10 months ago

Clinical data • Journal • Real-world evidence • Real-world

TP53 (Tumor protein P53) • RUNX1 (RUNX Family Transcription Factor 1)

TP53 mutation • RUNX1 mutation

10ms

Integrated characterization of hepatobiliary tumor organoids provides a potential landscape of pharmacogenomic interactions. (PubMed, Cell Rep Med)

RUNX1 promoter mutation is associated with an increase in chromatin accessibility and a concomitant gene expression increase, promoting a cluster of drugs preferentially sensitive in hepatobiliary tumors. These results not only provide an annotated PDHO biobank of human liver cancer but also suggest a systematic approach for obtaining a comprehensive understanding of the gene-regulatory network of liver cancer, advancing the applications of potential personalized medicine.

10 months ago

Journal

RUNX1 (RUNX Family Transcription Factor 1)

RUNX1 mutation

10ms

Venetoclax Added to Fludarabine + Busulfan Prior to Transplant and to Maintenance Therapy for AML, MDS, and MDS/MPN (clinicaltrials.gov)

P1, N=100, Recruiting, Jacqueline Garcia, MD | Trial completion date: Dec 2024 --> Feb 2026 | Trial primary completion date: Feb 2024 --> Feb 2025

10 months ago

Trial completion date • Trial primary completion date • Combination therapy

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BCR (BCR Activator Of RhoGEF And GTPase) • BCL2 (B-cell CLL/lymphoma 2) • NPM1 (Nucleophosmin 1) • NF1 (Neurofibromin 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • MECOM (MDS1 And EVI1 Complex Locus) • NUP214 (Nucleoporin 214) • GATA2 (GATA Binding Protein 2) • DEK (DEK Proto-Oncogene) • RIT1 (Ras Like Without CAAX 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

TP53 mutation • KRAS mutation • NRAS mutation • RUNX1 mutation • RAS mutation • ASXL1 mutation • CBL mutation • MLL rearrangement • U2AF1 mutation • Chr del(5q) • FLT3 wild-type

Venclexta (venetoclax) • azacitidine • Inqovi (decitabine/cedazuridine) • fludarabine IV • busulfan

10ms

Increased RUNX1 mutations in breast cancer disease progression. (PubMed, Pathol Res Pract)

The level of RUNX1 mutations also increased gradually as patients got older and the peak was highest in the patients of 60-70 years old. Altogether, these data indicated that the mutated RUNX1 gene contributed to the progression of breast cancer and understanding of its regulatory mechanisms is crucial to therapeutically target this gene in the future.

10 months ago

Journal

ER (Estrogen receptor) • RUNX1 (RUNX Family Transcription Factor 1)

ER positive • RUNX1 mutation

11ms

Prognosis and risk factors for ASXL1 mutations in patients with newly diagnosed acute myeloid leukemia and myelodysplastic syndrome. (PubMed, Cancer Med)

Our study indicated that mutations in G646W or RUNX1 co-mutations are closely associated with a dismal clinical outcome in patients with AML and MDS harboring ASXL1 . Considering the poor prognosis and risk factors in patients with ASXL1 , more available treatments should be pursued.

11 months ago

Journal

NRAS (Neuroblastoma RAS viral oncogene homolog) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • STAG2 (Stromal Antigen 2) • SETBP1 (SET Binding Protein 1)

NRAS mutation • RUNX1 mutation • ASXL1 mutation • EZH2 mutation • SRSF2 mutation • STAG2 mutation

11ms

Imatinib to Increase RUNX1 Activity in Participants With Germline RUNX1 Deficiency (clinicaltrials.gov)

P1, N=78, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

11 months ago

Enrollment open

RUNX1 (RUNX Family Transcription Factor 1)

RUNX1 mutation

imatinib

11ms

Efficacy and Survival of Venetoclax Based Regimen in the Treatment of Acute Myeloid Leukemia (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)

VEN-based regimen can achieve a high response rate, especially in unfit AML with acceptable safety, and some patients can achieve MRD negative. It is also effective in NPM1-, IDH1/2-positive patients with long survival time.

11 months ago

Journal

TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • TET2 (Tet Methylcytosine Dioxygenase 2)

TP53 mutation • NPM1 mutation • RUNX1 mutation • TET2 mutation

Venclexta (venetoclax)

12ms

Runx1-R188Q germline mutation induces inflammation and predisposition to hematologic malignancies in mice. (PubMed, Blood Adv)

Finally, we demonstrate that Runx1R188Q predisposes to HM in cooperation with somatic mutations found in FPDHM, utilizing three mouse models. These studies establish a novel murine FPDHM model and demonstrate that germline Runx1 mutations induce a pre-malignant phenotype marked by bone marrow inflammation, selective expansion capacity, defective DNA-damage response, and predisposition to HM.

12 months ago

Preclinical • Journal

RUNX1 (RUNX Family Transcription Factor 1) • CD48 (CD48 Molecule) • CD86 (CD86 Molecule)

RUNX1 mutation

12ms

Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals RNA N6-methyladenosine modification associated with prognosis and drug resistance in acute myeloid leukemia. (PubMed, Front Immunol)

Notably, patients with the immune dysregulation subtype were sensitive to immunotherapy and chemotherapy. Collectively, our findings suggest that mA modification could be a potential therapeutic target for AML, and the identified subtypes could guide personalized therapy.

12 months ago

Journal • IO biomarker

RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ELAVL1 (ELAV Like RNA Binding Protein 1) • FMR1 (Fragile X Messenger Ribonucleoprotein 1) • IGF2BP3 (Insulin Like Growth Factor 2 MRNA Binding Protein 3) • YTHDF2 (YTH N6-Methyladenosine RNA Binding Protein 2)

RUNX1 mutation • KMT2A mutation • MLL mutation

12ms

Analysis of Safety and Efficacy of Avapritinib As Targeted Therapy for Pediatric Acute Myeloid Leukemia Patients with KIT Mutation after Transplantation (ASH 2023)

2 patients did not achieve continuous RUNX1: : RUNX1T1 negative after preemptive therapy with Decitabine (DAC) and donor lymph infusion (DLI), and then was treated with Avapritinib, one's RUNX1: : RUNX1T1 fusion achieved continuously negative after 1 month treatment of Avapritinib, the other's achieved continuous negative after 7 months treatment of Avapritinib. Avapritinib is safe and effective in the prophylactic and preemptive treatment of AML with KIT mutation after allo-HSCT in children, which provides a clinical drug for the prevention of relapse after transplantation.

12 months ago

Clinical

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

KIT mutation • RUNX1 mutation • KIT N822K • KIT exon 17 mutation • RUNX1-RUNX1T1 fusion • KIT fusion

decitabine • Ayvakit (avapritinib)

12ms

Salvage Autologous Peripheral Blood Stem Cell Transplantation after the Development of tMDS or AML in Multiple Myeloma Patients (ASH 2023)

Post transplant treatment included lenalidomide maintenance, followed by a variety of salvage regimens over the next 7 years including thalidomide, carfilzomib, daratumumab and pomalidomide...He received a second ASCT after melphalan 140 mg/m2 in Oct 2017 followed by recovery of normal blood counts...Case 3 = 65-year-old man with MM treated with bortezomib + dexamethasone followed by ASCT in Aug 2012...Six months of decitabine did not improve his blood counts...This approach was well tolerated and provided durable hematopoietic recovery. Second ASCT using banked autologous stem cells should be considered in such patients who are not otherwise candidates for allogeneic transplantation.

12 months ago

Clinical

TP53 (Tumor protein P53) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SETBP1 (SET Binding Protein 1)

TP53 mutation • Chr del(17p) • DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • SF3B1 mutation • Chr del(5q)

lenalidomide • bortezomib • decitabine • Darzalex (daratumumab) • carfilzomib • dexamethasone • pomalidomide • thalidomide • melphalan