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GENE:

RUNX1 (RUNX Family Transcription Factor 1)

News alerts, weekly reports and conference planners

LINC01094 promotes gastric cancer through dual targeting of CDKN1A by directly binding RBMS2 and HDAC1. (PubMed, Biol Direct)

The LINC01094-miR-128-3p-RUNX1 feedback loop downregulates CDKN1A and promotes GC cooperatively with RBMS2 and HDAC1. Furthermore, Ro 5-3335 may hold promising therapeutic potential in the treatment of GC. Hence, our study found an oncogenic lncRNA, LINC01094, which could be a promising target for cancer treatment and diagnosis.

2 days ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • HDAC1 (Histone Deacetylase 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • LINC01094 (Long Intergenic Non-Protein Coding RNA 1094) • MIR128 (MicroRNA 128) • RBMS2 (RNA Binding Motif Single Stranded Interacting Protein 2)

ARMH1 is a novel marker associated with poor pediatric AML outcomes that affect the fatty acid synthesis and cell cycle pathways. (PubMed, Front Oncol)

Further, we also established that ARMH1 is a key physical interactant of EZH2, associated with multiple cancers. Our findings underscore further evaluation of ARMH1 as a potential candidate for targeted therapies and stratification of aggressive pAML to improve outcomes.

7 days ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • CPT1A (Carnitine Palmitoyltransferase 1A)

Proteomic and metabolomic exploration in relapse acute myeloid leukemia bone marrow supernatant combined with genetic characteristics. (PubMed, BMC Cancer)

This study has revealed a significant correlation between protein expression in the bone marrow microenvironment of AML and three high-risk mutations: ASXL1, TP53, and RUNX1. Based on this finding, we further identified 227 differential proteins closely associated with these three mutations, as well as 57 proteins directly related to disease recurrence. Additionally, lipid metabolism plays a crucial role in the occurrence and development of AML within its bone marrow microenvironment.

8 days ago

Journal • Metabolomic study

TP53 (Tumor protein P53) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1)

TP53 mutation • RUNX1 mutation • ASXL1 mutation

RUNX1::CBFA2T2 rearranged acute myeloid leukemia transformed from JAK2 V617F mutated primary myelofibrosis. (PubMed, EJHaem)

The immunophenotype and the landscape of cooperative gene alterations in AML with RUNX1::CBFA2T2 resemble those of AML with RUNX1::RUNX1T1, including expression of CD19, cooperative gene alterations in signaling pathway (JAK2), epigenetic/chromatin and cell cycle regulation (TET2, SMC3, and CDKN2A/B), and additional chromosomal abnormalities (trisomies 8 and 15). This case study provides insights into the pathogenesis of this rare subtype of AML.

9 days ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • JAK2 (Janus kinase 2) • CD19 (CD19 Molecule) • RUNX1 (RUNX Family Transcription Factor 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1)

CD19 expression • JAK2 V617F • JAK2 mutation

11d

Clinical characteristics and prognostic analysis of CDKN2A/2B gene in pediatric acute lymphoblastic leukemia: a retrospective case-control study. (PubMed, Hematology)

In conclusion, while ALL that does have CDKN2A/2B gene deletions is associated with certain clinical characteristics and genetic aberrations, they did not significantly impact OS or EFS. Furthermore, subgroup analysis revealed a potential prognostic role of ALL that does have CDKN2A/2B deletions presenting with hepatosplenomegaly on palpation, emphasizing the importance of comprehensive risk stratification in treatment decision-making for this subgroup.

11 days ago

Retrospective data • Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RUNX1 (RUNX Family Transcription Factor 1) • ETV6 (ETS Variant Transcription Factor 6) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

CDKN2A deletion

12d

Exploring immune gene expression and potential regulatory mechanisms in anaplastic thyroid carcinoma using a combination of single-cell and bulk RNA sequencing data. (PubMed, Comput Biol Chem)

The nine CIG-related TFs (CEBPB, SPI1, NFKB1, RUNX1, NFE2L2, REL, CIITA, KLF6, and CEBPD) in myeloid cells and three TFs (NFKB1, FOXO1, and NR3C1) in T/NK cells were obtained from the TRRUST database. The key genes we identified represent potential targets for treating ATC.

12 days ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • B2M (Beta-2-microglobulin) • NFKB1 (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) • SPI1 (Spi-1 Proto-Oncogene) • TNFRSF1B (TNF Receptor Superfamily Member 1B)

13d

Next-generation sequencing RNA fusion panel for the diagnosis of haematological malignancies. (PubMed, Pathology)

These findings confirm the unique utility of the NGS-based RNA fusion panel as a diagnostic tool to identify gene rearrangements that drive haematological malignancies. It can identify novel and rare gene rearrangements to assist with diagnosis, prognostication and treatment decisions.

13 days ago

Journal • Next-generation sequencing

ABL1 (ABL proto-oncogene 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • CREBBP (CREB binding protein) • AFF1 (AF4/FMR2 Family Member 1) • FIP1L1 (Factor Interacting With PAPOLA And CPSF1) • KAT6A (Lysine Acetyltransferase 6A) • MLLT3 (MLLT3 Super Elongation Complex Subunit)

14d

BMT-06: Study of Intensity Modulated Total Marrow Irradiation (IM-TMI) (clinicaltrials.gov)

P2, N=27, Recruiting, University of Illinois at Chicago | Trial completion date: Nov 2024 --> Dec 2026 | Trial primary completion date: Nov 2024 --> Dec 2026

14 days ago

Trial completion date • Trial primary completion date • Post-transplantation

RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • HLA-DQB1 (Major Histocompatibility Complex, Class II, DQ Beta 1) • HLA-B (Major Histocompatibility Complex, Class I, B)

RUNX1 mutation • ASXL1 mutation • MLL rearrangement • MLL rearrangement • MLL translocation

cyclophosphamide • fludarabine IV

14d

Acute myeloid leukemia associated RUNX1 variants induce aberrant expression of transcription factor TCF4. (PubMed, Leukemia)

No abstract available

14 days ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • TCF4 (Transcription Factor 4)

16d

Efficacy of Midostaurin Combined With Intensive Chemotherapy in Core Binding Factor Leukemia: A Phase II Clinical Trial. (PubMed, Am J Hematol)

Patients who achieved CR or CRi received 3 courses of high-dose ARA-C (Cytarabine) 3000 mg/m2 every 12 h on days 1, 3, and 5, along with midostaurin at the dose of 50 mg b.i.d from Day 8 to Day 21 as part of consolidation therapy. The RI was 38.8% in the CBFB::MYH11 and 66.6% in the RUNX1::RUNX1T1 group. MRD (Measurable Residual Disease) was assessed by RQ-PCR at 10 time points throughout the study, as indicated by arrows.

16 days ago

P2 data • Journal

RUNX1 (RUNX Family Transcription Factor 1) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1)

cytarabine • Rydapt (midostaurin)

17d

Megakaryocyte centrosomal and Golgi structural perturbations in patients with primary myelofibrosis and with RUNX1 germline mutation. (PubMed, Leuk Lymphoma)

No abstract available

17 days ago

Journal

RUNX1 (RUNX Family Transcription Factor 1)

RUNX1 mutation

18d

Genome-wide Mendelian randomization identifies drugs associated with body height. (PubMed, Transl Pediatr)

Interactive drugs were identified, including amoxicillin, atenolol, infliximab, colchicine, propionyl-L-carnitine, BMN-111, and tamoxifen, which were known to have a positive effect on height. Our results suggest that many genes have causal effects on height. By interrogating drug-gene interactions, interactive drugs have been identified as having both positive and negative effects on growth, which would help make clinical decisions.

18 days ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • GNA12 (G Protein Subunit Alpha 12) • HLA-C (Major Histocompatibility Complex, Class I, C) • ZBTB38 (Zinc Finger And BTB Domain Containing 38) • BTN2A2 (Butyrophilin Subfamily 2 Member A2)

tamoxifen

20d

A Comprehensive Whole Genome Sequencing Assay Provides Robust Characterization of Clinically Relevant Genomic Alterations across Myeloid Malignancies Concordant with Matched Results from Targeted DNA, Whole Transcriptome RNA and Cytogenetic Profiling (ASH 2024)

Additionally, WGS can identify unique SVs that may be missed by conventional methods and enables clinical benefits such as HLA typing for potential transplant (alloHCT) or diagnostic refinement by retroviral insertion (e.g. HTLV-1). These findings demonstrate the potential for integration of WGS into clinical practice to enhance personalized treatment strategies.

20 days ago

Clinical • Discordant • Whole genome sequencing

FLT3 (Fms-related tyrosine kinase 3) • RUNX1 (RUNX Family Transcription Factor 1) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1)

Tempus xT Assay • Tempus xR

20d

SF3B1 Gene Mutations and Their Significance for Patients with Myelodysplastic Neoplasms (MDS) (ASH 2024)

Three are still alive and are undergoing azacitidine treatment at 6.5, 8.5, and 21 months after their diagnosis.Identification of splicing factor gene mutations is an important diagnostic tool for the stratification of MDS patients...Other biological factors such as the mutation variant, association with complex karyotypes, and mutations in other genes, may also affect the prognosis of patients with mutated SF3B1. Therefore, a comprehensive view that includes all cytogenomic, molecular, and clinical data is important for accurate diagnosis and personalized treatment of MDS patients.Supported by MH CZ-DRO 0064165

20 days ago

Clinical

TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • 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) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2) • BCORL1 (BCL6 Corepressor Like 1)

TP53 mutation • NRAS mutation • TET2 mutation • SF3B1 mutation • SRSF2 mutation • U2AF1 mutation • Chr del(5q) • SF3B1 K666N • SF3B1 K700E

Archer® VariantPlex® Myeloid panel

azacitidine

20d

Comprehensive Genomic Profiling (CGP) of Acute Myeloid Leukemias with Foundation One Heme Identifies Actionable Genomic Alterations and Biomarkers (ASH 2024)

Current best practices for the diagnosis, classification, prognostication, and treatment of AML call for the assessment of the presence and absence of numerous genomic alterations. Therefore, in contrast to single-gene or small-panel molecular testing, the F1H platform can simplify such assessment via a CGP approach.

20 days ago

IO biomarker

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • BCL2 (B-cell CLL/lymphoma 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • 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) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • BCOR (BCL6 Corepressor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • NUP214 (Nucleoporin 214) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • MRTFA (Myocardin Related Transcription Factor A) • RBM15 (RNA Binding Motif Protein 15)

TP53 mutation • NPM1 mutation • KMT2A rearrangement • MLL rearrangement • U2AF1 mutation • CEBPA mutation • MLL mutation • NPM1 W288

FoundationOne® Heme CDx

22d

ECOG-ACRIN E1910: Combination Chemotherapy With or Without Blinatumomab in Treating Patients With Newly Diagnosed BCR-ABL-Negative B Lineage Acute Lymphoblastic Leukemia (clinicaltrials.gov)

P3, N=488, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Mar 2025

22 days ago

Trial completion date

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RUNX1 (RUNX Family Transcription Factor 1) • IGH (Immunoglobulin Heavy Locus) • ETV6 (ETS Variant Transcription Factor 6) • CD4 (CD4 Molecule) • TCF3 (Transcription Factor 3) • PBX1 (PBX Homeobox 1)

Rituxan (rituximab) • cytarabine • cyclophosphamide • etoposide IV • Blincyto (blinatumomab) • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • Truxima (rituximab-abbs) • mercaptopurine • Hemady (dexamethasone tablets) • Mabtas (rituximab biosimilar) • Starasid (cytarabine ocfosfate)

28d

Molecular landscape and clinical outcome of SRSF2/TET2 Co-mutated myeloid neoplasms. (PubMed, Leuk Lymphoma)

We found that ASXL1, RUNX1, and KRAS can negatively impact these patients' survival with different impacts in different morphological diagnosis categories, suggesting a complex interaction between these genes. This study underscores the need for personalized approaches in the treatment of myeloid neoplasms.

28 days ago

Clinical data • Journal

KRAS (KRAS proto-oncogene GTPase) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2)

ASXL1 mutation • TET2 mutation • SRSF2 mutation

29d

Identification of a Novel RUNX1::STX2 Fusion in Mixed-Phenotype Acute Leukemia (MPAL) With BCR::ABL1. (PubMed, Mol Carcinog)

The RUNX1::STX2 fusion protein may act as the primary negative regulator of wild-type RUNX1, influencing normal cell differentiation and proliferation, consequently elevating the risk of leukemia. The gene fusion status of this patient is unique and complex, requiring further exploration to understand its functional significance in leukemia progression and treatment response.

29 days ago

Journal

ABL1 (ABL proto-oncogene 1) • RUNX1 (RUNX Family Transcription Factor 1)

ABL1 fusion • BCR expression

Recurrent PAX5::ZCCHC7 rearrangement in B-cell acute lymphoblastic leukemia. (PubMed, Ann Hematol)

In summary, the PAX5::ZCCHC7 is a recurrent genetic aberration in B-ALL and seems to act as an additional genetic abnormality of subtype-defining aberration. Whether the PAX5::ZCCHC7 could act as a leukemia-initiating event or not needs further investigation.

1 month ago

Journal

ABL1 (ABL proto-oncogene 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • ETV6 (ETS Variant Transcription Factor 6) • CRLF2 (Cytokine Receptor Like Factor 2) • PAX5 (Paired Box 5) • TCF3 (Transcription Factor 3)

PAX5 deletion

Copy number alterations in pediatric B-cell precursor acute lymphoblastic leukemia patients and their association with patients' outcome. (PubMed, Ann Hematol)

PAX5 CNA is an adverse prognostic factor. ETV6 CNA is associated with high MRD on day 15.

1 month ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • ETV6 (ETS Variant Transcription Factor 6) • PAX5 (Paired Box 5)

Rapid Screening to Identify Antivirals against Persistent and Acute Coxsackievirus B3 Infection. (PubMed, ACS Infect Dis)

We also show efficacy against other RNA viruses, but it is ineffective against a model DNA virus. Overall, Ro 5-3335 is a promising antiviral that may target CVB3 infection.

1 month ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • CBFB (Core-Binding Factor Subunit Beta 2)

Combatting cellular immortality in cancers by targeting the shelterin protein complex. (PubMed, Biol Direct)

Insights into TPP1-associated glycans highlighted glycosylated sites contributing to tumorigenesis. This study provides molecular signatures for further functional and therapeutic research on shelterin, highlighting its potential as a target for anti-cancer therapies and promising prospects for cancer prognosis and prediction.

1 month ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • POT1 (Protection of telomeres 1) • TERF1 (Telomeric Repeat Binding Factor 1) • TINF2 (TERF1 Interacting Nuclear Factor 2) • TPP1 (Tripeptidyl Peptidase 1)

The co-receptor Neuropilin-1 enhances proliferation in inv(16) acute myeloid leukemia via VEGF signaling. (PubMed, Leukemia)

Finally, we show that treatment with VEGF inhibitor axitinib reduces AML cell growth and delays median leukemia latency in vivo. Our findings reveal that the NRP1/VEGF axis mediates proliferation in inv(16) AML blasts, and suggest that targeting NRP1 function could be promising in combination AML therapy.

1 month ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • ERG (ETS Transcription Factor ERG) • GATA2 (GATA Binding Protein 2) • CBFB (Core-Binding Factor Subunit Beta 2) • NRP1 (Neuropilin 1)

Inlyta (axitinib)

Molecular Analysis of Genes CEBPA, NPM1, IDH1, and RUNX1 Polymorphisms as Biomarker Potential in Leukemia Patients. (PubMed, Mol Carcinog)

Leukemia risk increases by twofold and shows significant association in the homozygous mutant (AA) of rs11554137 (OR = 1.75; 95%Cl = 1.09-2.79; p = 0.01). Leukemia risk increases by twofold and shows significant association in the homozygous mutant (AA) of rs13051066 of gene RUNX1 (OR = 0.63; 95%Cl = 0.39-1.63; p = 0.06).

1 month ago

Journal

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha)

WBP1L regulates hematopoietic stem cell function and T cell development. (PubMed, Front Immunol)

In addition, we show that WBP1L regulates hematopoietic stem cell functionality and leukocyte progenitor proliferation and gene expression during hematopoietic stem and progenitor cell transplantation, which contribute to more efficient engraftment of WBP1L-deficient cells. WBP1L thus emerges as a regulator of hematopoietic stem and progenitor cell function, which controls leukocyte numbers at the steady state and after bone marrow transplantation.

1 month ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • ETV6 (ETS Variant Transcription Factor 6)

Redistribution of PU.1 partner transcription factor RUNX1 binding secures cell survival during leukemogenesis. (PubMed, EMBO J)

Control of this program involves redirected chromatin occupancy of the PU.1 partner TF Runx1 to a lineage-inappropriate binding site repertoire. Hence, genomic reallocation of TF binding upon loss of a partner TF can act as a pro-oncogenic failsafe mechanism by sustaining cell survival during leukemogenesis.

1 month ago

Journal

RUNX1 (RUNX Family Transcription Factor 1)

Olfactory Neuroblastoma With Divergent Differentiation: Contemporary Management of Unusual Pathology and Literature Review. (PubMed, Ear Nose Throat J)

We are the first group to report next-generation sequencing of this tumor, which revealed a pathogenic mutation in PIK3CA and a likely pathogenic variant in RUNX1 (AML1). ON with divergent differentiation is very rare, and more robust studies characterizing molecular drivers and pathology may aid in clinical management.

1 month ago

Review • Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • RUNX1 (RUNX Family Transcription Factor 1) • SYP (Synaptophysin)

PIK3CA mutation • ROS1 positive

ARF alters PAF1 complex integrity to selectively repress oncogenic transcription programs upon p53 loss. (PubMed, Mol Cell)

Notably, pharmacologic inactivation of GDF/BMP signaling and genetic perturbation of RUNX1 significantly attenuate cell proliferation mediated by dual p53 and ARF loss, offering therapeutic utility. Our data underscore the significance of selective ARF-mediated tumor-suppressive functions through a universal transcriptional regulator.

1 month ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • PAF1 (PAF1 Homolog, Paf1/RNA Polymerase II Complex Component)

A RUNX1: RUNX1T1 AML with a simultaneous false positive KMT2A rearrangement: FISH interpretation pitfalls. (PubMed, Hematology)

Given that KMT2A FISH probes cover approximately 1 Mb around KMT2A, this subtle shift led to a split-apart signal pattern mimicking a genuine KMT2A rearrangement, resulting in a false positive FISH interpretation. This case highlights a false positive KMT2Ar in primary AML, indicating the need for additional molecular testing for confirmation.

1 month ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1)

KMT2A rearrangement • MLL rearrangement • RUNX1-RUNX1T1 fusion • MLL fusion

AALL1131: Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations (clinicaltrials.gov)

P3, N=5949, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Oct 2025

1 month ago

Trial completion date

MLL rearrangement • MLL rearrangement

dasatinib • cytarabine • doxorubicin hydrochloride • cyclophosphamide • etoposide IV • methotrexate • vincristine • daunorubicin • clofarabine • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • thioguanine • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate)

Evaluation of OGT's SureSeq Myeloid Fusion Complete NGS Workflow Solution V2 for Partner-Agnostic Fusion Gene Detection in Acute Leukemias (AMP 2024)

We demonstrated the capability of OGT's SureSeq Myeloid Fusion Complete NGS Workflow Solution V2 to achieve 100% accurate detection for novel and canonical translocations. By allowing concurrent detection of multiple known and novel rearrangements, NGS assays offer an economical and efficient alternative to routine cytogenetic approaches.

1 month ago

Next-generation sequencing

ABL1 (ABL proto-oncogene 1) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • MECOM (MDS1 And EVI1 Complex Locus) • HOXD8 (Homeobox D8)

KMT2A rearrangement • MLL rearrangement

SureSeq™ Myeloid Fusion Panel

DNA and RNA NGS for Myeloid Neoplasms Using Oncomine Myeloid Assay GX v2 on GeneXus: An Assessment of Clinical Utility (AMP 2024)

This DNA- and RNA-based 80-gene panel has proven to be a powerful tool for genomic profiling of myeloid neoplasms. The results were provided to hematopathologists/oncologists in timely fashion with the critical information for diagnosis confirmation, and disease classification, as well as assessment of patient response to treatment.

1 month ago

Clinical • Next-generation sequencing

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) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • 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) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • DDX41 (DEAD-Box Helicase 41) • CALR (Calreticulin) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

FLT3-ITD mutation • NPM1 mutation • U2AF1 mutation • CEBPA mutation • JAK2 V617F

Oncomine Myeloid Assay GX

Capturing Fusion in Hematological Malignancies through Targeted RNASeq (AMP 2024)

We have demonstrated the capability of the SureSeq Myeloid Fusion Complete NGS Workflow Solution to detect known rearrangements in AML. We observed 100% concordance with qPCR and FISH for all samples tested. The NGS data permitted single-exon resolution of breakpoints and revealed the presence of multiple breakpoints which would have remained undetected with FISH.

1 month ago

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • AFF1 (AF4/FMR2 Family Member 1) • PML (Promyelocytic Leukemia) • MECOM (MDS1 And EVI1 Complex Locus) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • AFDN (Afadin, Adherens Junction Formation Factor) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor)

BCR-ABL1 fusion • MLL fusion

SureSeq™ Myeloid Fusion Panel

2ms

Development and Validation of a Biopsy-Free Scoring System for Screening Myelodysplastic Syndrome (MDS) and Associated Diseases in Cytopenic Patients (ASH 2024)

For patients with a probability score < 45%, a bone marrow study may not be needed, with a recommended follow-up every 6–12 months. This comprehensive analysis provides a useful and non-invasive predictive model that enhances diagnostic accuracy which potentially reduces unnecessary procedures.

2 months ago

Clinical • Biopsy

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) • 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) • 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) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • SETBP1 (SET Binding Protein 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

TP53 mutation • KRAS mutation • NRAS mutation • IDH2 mutation • NPM1 mutation • ASXL1 mutation • TET2 mutation • SF3B1 mutation • SRSF2 mutation • U2AF1 mutation

Oncomine Myeloid Research Assay

2ms

Prognostic Role of NGS-Based MRD Assessment in FLT3-TKD Mutated Patients with Acute Myeloid Leukemia (ASH 2024)

Only two patients in the MRD negative group received the FLT3 inhibitor midostaurin combined with chemotherapy...NGS-MRD was not prognostic in this cohort of FLT3-TKD mutated AML patients. Shared first authors : Isabell Arnhardt, Christian M Vonk Shared senior authorship : Michael Heuser, Peter J.M. Valk

2 months ago

Clinical • Next-generation sequencing

FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NPM1 (Nucleophosmin 1) • 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)

FLT3-ITD mutation • NPM1 mutation • ASXL1 mutation • TET2 mutation • SF3B1 mutation • FLT3-TKD mutation

TruSight Myeloid Sequencing Panel

Rydapt (midostaurin)

2ms

Comprehensive Genomic Profiling (CGP) of Acute Lymphoblastic Leukemias with Foundation One Heme Identifies Actionable Genomic Alterations and Biomarkers (ASH 2024)

Conclusions : This analysis of 2,637 samples comprising a variety of molecular subtypes of ALL demonstrated that the F1H assay detects pathogenic genomic alterations with diagnostic, prognostic, and therapeutic significance. As both the treatment landscape and disease classification system in ALL have continued to evolve over time, CGP assays such as F1H can play a critical role in clinical decision making by simultaneously assessing the presence and absence of numerous actionable genomic alterations and biomarkers with a single assay.

2 months ago

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • CRLF2 (Cytokine Receptor Like Factor 2) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • PAX5 (Paired Box 5) • TCF3 (Transcription Factor 3) • P2RY8 (P2Y Receptor Family Member 8) • PBX1 (PBX Homeobox 1) • ABL2 (ABL Proto-Oncogene 2, Non-Receptor Tyrosine Kinase)

TP53 mutation • KRAS mutation • NRAS mutation • PTEN mutation • CDKN2A deletion

FoundationOne® Heme CDx

2ms

KMT2A (MLL1) Rearrangements in Hematolymphoid Malignancies: A Genomic Landscape Study (ASH 2024)

Conclusions : Rearrangements in the KMT2A gene in AML are common and may emerge as a new target of therapy for AML patients. This genomic landscape study reveals significant differences in import GA associated with AML in KMT2Ara and KMT2Anra cases.

2 months ago

Tumor mutational burden

KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • WT1 (WT1 Transcription Factor)

KRAS G12C • KMT2A rearrangement • KRAS G12 • MLL rearrangement • MLL rearrangement • MLL mutation

FoundationOne® Heme CDx

2ms

Longitudinal Sequencing to Investigate Clonal Evolution in Myeloid Neoplasms (ASH 2024)

Ongoing work would further dissect the exact impact of resistant/relapse signature and a weighted impact on survival and outcomes. Ongoing analysis in other disease groups will be presented at the ASH conference.

2 months ago

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • STAG2 (Stromal Antigen 2)

TP53 mutation

TruSight Myeloid Sequencing Panel

2ms

Genome-first determination of the prevalence and penetrance of eight germline myeloid malignancy predisposition genes: a study of two population-based cohorts. (PubMed, Leukemia)

Pathogenic DDX41 variants were the most commonly identified, and in UKBB showed a significantly increased risk of MM (OR 5.7 [95% CI 3.9-8.3], p = 6.0 × 10-20) and increased all-cause mortality (HR 1.35 [95% CI 1.1-1.7], p = 0.0063). Through a genome-first approach, this study genetically ascertained individuals with a gMMP and determined their MM risk and survival.

2 months ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • ETV6 (ETS Variant Transcription Factor 6) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • MECOM (MDS1 And EVI1 Complex Locus) • DDX41 (DEAD-Box Helicase 41) • GATA2 (GATA Binding Protein 2) • ANKRD26 (Ankyrin Repeat Domain Containing 26)

2ms

Potential molecular mechanisms of ETV6-RUNX1-positive B progenitor cell cluster in acute lymphoblastic leukemia revealed by single-cell RNA sequencing. (PubMed, PeerJ)

HLAE-KLRC1 and TGFB1-(TGFBR1+TGFBR2). This study outlined the immune cell landscape of ETV6-RUNX1 ALL and identified chromosome 6p amplification in B progenitor cells, described the major B progenitor cell cluster driving cell cycle progression and its potential regulatory mechanisms on NK cells and T cells, providing cellular and molecular insights into ETV6-RUNX1 ALL.

2 months ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • ETV6 (ETS Variant Transcription Factor 6) • TGFBR2 (Transforming Growth Factor Beta Receptor 2) • HLA-E (Major Histocompatibility Complex, Class I, E) • TGFB1 (Transforming Growth Factor Beta 1) • E2F1 (E2F transcription factor 1) • KLRC1 (Killer Cell Lectin Like Receptor C1) • KLRC2 (Killer Cell Lectin Like Receptor C2) • TGFBR1 (Transforming Growth Factor Beta Receptor 1)

Chr amplification(6p)

2ms

Inducible Pluripotent Stem Cell Models to Study Bone Marrow Failure and MDS Predisposition Syndromes. (PubMed, Exp Hematol)

The review also explores future directions, including the potential of iPSC models for drug discovery and personalized medicine approaches. This review underscores the significance of iPSC technology in advancing our understanding of inherited hematopoietic disorders and its potential to inform novel therapeutic strategies.

2 months ago

Review • Journal

RUNX1 (RUNX Family Transcription Factor 1) • ETV6 (ETS Variant Transcription Factor 6) • ALDH2 (Aldehyde Dehydrogenase 2 Family Member) • GATA2 (GATA Binding Protein 2) • ANKRD26 (Ankyrin Repeat Domain Containing 26)

2ms

Transcriptional regulatory program controlled by MYB in T-cell acute lymphoblastic leukemia. (PubMed, Leukemia)

Their expression can be recovered at later time-points, suggesting the presence of a negative feedback loop mechanism. In contrast, late response genes, which are continuously downregulated after MYB depletion, includes many genes involved in cell proliferation as well as TAL1 targets, thereby affecting the cellular phenotype.

2 months ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • IKZF2 (IKAROS family zinc finger 2) • GATA3 (GATA binding protein 3)

CXCR4 expression