News - RUNX1 mutation

17h

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.

17 hours ago

Journal

RUNX1 (RUNX Family Transcription Factor 1)

RUNX1 mutation

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.

1 day ago

Journal • Biopsy

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

RUNX1 mutation • U2AF1 mutation

decitabine

14d

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

14 days 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)

24d

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.

24 days 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

29d

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.

29 days 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

30d

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.

30 days 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

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.

1 month 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)

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.

1 month ago

Journal

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

RUNX1 mutation

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.

1 month ago

Journal • Real-world evidence • Real-world

RUNX1 (RUNX Family Transcription Factor 1)

RUNX1 mutation

Venclexta (venetoclax)

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.

1 month 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

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

1 month 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

2ms

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.

2 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

2ms

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.

2 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

2ms

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

2 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)

2ms

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 .

2 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

2ms

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.

2 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

2ms

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.

2 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

3ms

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.

3 months ago

Journal

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

TP53 mutation • RUNX1 mutation

3ms

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.

3 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

3ms

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.

3 months ago

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

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

TP53 mutation • RUNX1 mutation

3ms

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.

3 months ago

Journal

RUNX1 (RUNX Family Transcription Factor 1)

RUNX1 mutation

3ms

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

3 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

3ms

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.

3 months ago

Journal

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

ER positive • RUNX1 mutation

4ms

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.

4 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

4ms

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

4 months ago

Enrollment open

RUNX1 (RUNX Family Transcription Factor 1)

RUNX1 mutation

imatinib

4ms

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.

4 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)

5ms

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.

5 months ago

Preclinical • Journal

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

RUNX1 mutation

5ms

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.

5 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

5ms

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.

5 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

5ms

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.

5 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)

5ms

Safety and Efficacy of Azacitidine and Chidamide Maintenance after Allogeneic Hematopoietic Stem Cell Transplantation for Patients with High-Risk Acute Myeloid Leukemia: Interim Analysis of a Prospective, Multicenter, Single-Arm, Phase Ⅱ Clinical Trial (ASH 2023)

ConclusionsPreliminary results suggest that maintenance of AZA combined with chidamide post allo-HSCT in patients with high-risk AML exhibits promising efficacy and well-tolerated. Recruitment of patients with high-risk AML post allo-HSCT for this trial is ongoing.

5 months ago

Clinical

TP53 (Tumor protein P53) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A)

TP53 mutation • RUNX1 mutation • KMT2A rearrangement • MLL rearrangement

azacitidine • Epidaza (chidamide)

5ms

Co-Mutational Patterns with BCOR Influences Biological Characteristics and Clinical Outcomes of Myeloid Neoplasms (ASH 2023)

Furthermore, patients with BCORMT, ASXL1MT, and concomitant DNA methylation-related gene mutations had worse outcomes compared to those with concomitant spliceosome mutation and BCORWT. Our findings suggest that co-mutational patterns of BCOR may further clarify diagnosis and classification schemes, highlighting potential synergies among subcategories of gene mutations and their prognostic value.

5 months ago

Clinical • Clinical data

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • BCL6 (B-cell CLL/lymphoma 6) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

NPM1 mutation • DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • TET2 mutation • U2AF1 mutation • BCOR mutation

5ms

Efficacy and Safety Analysis of Venetoclax Combined with Azacitidine in Real-World Treatment of Patients with AML (ASH 2023)

In the real world first-line treatment of high-risk AML patients with Ven combined with AZA, the disease control and survival were initially improved, and the early combined response rate (CR+CRi) of molecular subgroups IDH1/2, NPM1, RUNX1, ASXL1, FLT3-ITD and HOX11 were higher. The higher incidence of adverse events in early treatment and delayed treatment may be related to 41. 9% of patients with grade 3 neutropenia at baseline, partly AML-MRC.

5 months ago

Clinical • HEOR • Real-world evidence • Real-world

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TLX1 (T Cell Leukemia Homeobox 1)

TP53 mutation • KRAS mutation • NRAS mutation • FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • RUNX1 mutation • ASXL1 mutation

Venclexta (venetoclax) • azacitidine

5ms

Frameshift Mutations in Leukemia Associated Genes Correlate with Superior Outcomes in Patients Undergoing Allogeneic Stem Cell Transplant for De Novo Acute Myeloid Leukemia Compared to Other Types of Mutations (ASH 2023)

ConclusionThough limited by small sample size, our data suggest that frameshift mutated AML cases may benefit more from allo-SCT than those with only non-FS mutations, possibly due to increased generation of immunogenic neoepitopes. If validated in larger studies, incorporation of somatic frameshift mutation status in AML risk stratification models could improve existing patient selection algorithms for bone marrow transplant and thereby lead to superior outcomes.

5 months ago

Clinical

TP53 (Tumor protein P53) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • WT1 (WT1 Transcription Factor) • BCOR (BCL6 Corepressor) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • PHF6 (PHD Finger Protein 6) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

TP53 mutation • DNMT3A mutation • RUNX1 mutation • TET2 mutation

5ms

Mutational Burden in High Risk Genes Do Not Affect Remission Rates and MRD Clearance in Elderly AML Patients Receiving CPX-351 Induction (ASH 2023)

CPX-351 is able to induce good quality remission with high CR rate and MRD negativity, regardless of mutational burden, allowing a high number of elderly AML patients to undergo to HSCT. MRD evaluation has proven to be a strong prognostic tool also in the setting of elderly s-AML and t-AML patients receiving CPX-351. The prognostic value of high risk mutation seems to be less relevant in CPX-351 treated patients.

5 months ago

Clinical • Tumor mutational burden

TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2)

TP53 mutation • TMB-H • RUNX1 mutation • SRSF2 mutation

Vyxeos (cytarabine/daunorubicin liposomal formulation)

5ms

RTK-RAS Signaling Pathway Was Enriched in Rare Acute Myeloid Leukemia Patients with t(16; 21)(p11; q22)/ FUS: : ERG (ASH 2023)

PTPN11 and NRAS were the most frequent mutations and RTK-RAS signaling pathway was the most involved pathway in rare AML patients with t(16; 21)(p11; q22)/ FUS: : ERG. The addition of signaling pathway inhibitors followed by HSCT might be an effective strategy to overcome the dismal outcome of this subtype. Larger cohort studies are warranted to investigate the molecular characteristics further as well as evaluate the clinical activity of the SHP2 (PTPN11) inhibitors in FUS: : ERG AML patients.

5 months ago

Clinical

ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • BCOR (BCL6 Corepressor) • CD123 (Interleukin 3 Receptor Subunit Alpha) • NCAM1 (Neural cell adhesion molecule 1) • FUS (FUS RNA Binding Protein) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • SH2B3 (SH2B Adaptor Protein 3)

KRAS mutation • NRAS mutation • DNMT3A mutation • RUNX1 mutation • RAS mutation • ASXL1 mutation • PTPN11 mutation • NRAS Q61 • BCOR mutation • NRAS G12

5ms

Integrative Multi-Omic Analysis for Prognosis Stratification in Acute Myeloid Leukemia (ASH 2023)

Receptor tyrosine kinase signaling inhibitors (SB505124 and EphB4) might be sensitive to UAMOCS1. Taken together, UAMOCS model was generated that can classify AML patients independently and help develop precise chemotherapeutic strategy for patients with AML in the future.

5 months ago

Omic analysis

RUNX1 (RUNX Family Transcription Factor 1) • EPHB4 (EPH receptor B4) • MOCS2 (Molybdenum Cofactor Synthesis 2) • MOCS3 (Molybdenum Cofactor Synthesis 3)

RUNX1 mutation