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GENE:

RUNX1 (RUNX Family Transcription Factor 1)

News alerts, weekly reports and conference planners

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.

2 days 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.

4 days 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.

5 days 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.

7 days 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.

7 days 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

8 days 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)

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.

8 days 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.

8 days 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

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.

8 days 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

15d

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.

15 days 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 • STAG2 mutation

Oncomine Myeloid Research Assay

15d

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

15 days 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 • DNMT3A mutation • ASXL1 mutation • TET2 mutation • SF3B1 mutation • FLT3-TKD mutation

TruSight Myeloid Sequencing Panel

Rydapt (midostaurin)

15d

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

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.

15 days 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

15d

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

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.

15 days 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

15d

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

We analyzed 851 patients with MN at Karmanos Cancer Institute; 444 with serial samples. Among these patients, 174 (39%) had primary AML (pAML), 144 (32%) had secondary AML (sAML), 58 (13%) had MDS, 18 (4%) had MDS/MPN and 50 (11%) had MPN. Median age for primary AML was 56 ys (19-82), secondary AML was 64 ys (31-86) and MDS was 66 ys (23-90).

15 days 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 • DNMT3A mutation • STAG2 mutation

TruSight Myeloid Sequencing Panel

16d

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.

16 days 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)

16d

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.

16 days 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)

17d

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.

17 days 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)

18d

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.

18 days 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

20d

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.

20 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

24d

Prognostic impact of next-generation sequencing on myelodysplastic syndrome: A single-center experience. (PubMed, Medicine (Baltimore))

According to early findings, NGS panels are extremely effective instruments that provide an entirely new viewpoint on the disease for particular individuals. Future prognostications will depend more on NGS because those who exhibit normal cytogenetics may additionally have gene mutations.

24 days ago

Journal • Next-generation sequencing

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • 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) • ETV6 (ETS Variant Transcription Factor 6) • SRSF2 (Serine and arginine rich splicing factor 2) • CSF3R (Colony Stimulating Factor 3 Receptor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • SETBP1 (SET Binding Protein 1) • DDX41 (DEAD-Box Helicase 41) • GATA2 (GATA Binding Protein 2) • PHF6 (PHD Finger Protein 6)

ASXL1 mutation • TET2 mutation • SF3B1 mutation • EZH2 mutation • SRSF2 mutation • U2AF1 mutation • PHF6 mutation

26d

Blast Transformation of Chronic Myeloid Leukemia Driven by Acquisition of t(8;21)(q22;q22)/RUNX1::RUNX1T1: Selecting Optimal Treatment Based on Clinical and Molecular Findings. (PubMed, Biomedicines)

We report the case of a 63-year-old woman with a history of CML with poor response to imatinib who progressed to myeloid BP-CML, driven by the acquisition of t(8;21)(q22;q22)/RUNX1::RUNX1T1. The patient received intensive chemotherapy and dasatinib, followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT)...Ponatinib and azacitidine were started as salvage treatment, allowing for the achievement of complete remission with deep molecular response after five cycles. Advances in the knowledge of disease biology and clonal evolution are crucial for optimal treatment selection, which ultimately translates into better patient outcomes.

26 days ago

Journal

ABL1 (ABL proto-oncogene 1) • RUNX1 (RUNX Family Transcription Factor 1) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1)

ABL1 T315I

dasatinib • imatinib • Iclusig (ponatinib) • azacitidine

27d

Increased Cadmium Load, Vitamin D Deficiency, and Elevated FGF23 Levels as Pathophysiological Factors Potentially Linked to the Onset of Acute Lymphoblastic Leukemia: A Review. (PubMed, J Pers Med)

ALL has been observed in both IDA and thalassemia. However, as IDA is the most common type of anemia and the majority of published data pertains to it, we will focus on IDA in this review.

27 days ago

Review • Journal

RUNX1 (RUNX Family Transcription Factor 1) • ETV6 (ETS Variant Transcription Factor 6) • FGF23 (Fibroblast Growth Factor 23)

ETV6 mutation

27d

JMJD1C forms condensates to facilitate a RUNX1-dependent gene expression program shared by multiple types of AML cells. (PubMed, Protein Cell)

This dual capability of JMJD1C may influence enhancer-promoter contacts crucial for the expression of key leukemic genes regulated by RUNX1. Our findings demonstrate a previously unappreciated role for the non-catalytic function of JMJD1C in transcriptional regulation, underlying a mechanism shared by different types of leukemias.

27 days ago

Journal

RUNX1 (RUNX Family Transcription Factor 1)

29d

Genetic predisposition to myelodysplastic syndrome: Genetic counseling and transplant implications. (PubMed, Semin Hematol)

Furthermore, the role of hematopoietic cell transplantation in managing MDS, particularly in patients with germline syndromes, is reviewed, emphasizing the need for optimal donor selection and personalized treatment approaches. This comprehensive overview illustrates the critical role of genetic factors in MDS and highlights the need for continued research and tailored clinical practices to improve patient outcomes.

29 days ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • ETV6 (ETS Variant Transcription Factor 6) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • DDX41 (DEAD-Box Helicase 41) • ANKRD26 (Ankyrin Repeat Domain Containing 26)

30d

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%.

30 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)

Clinical features and long-term prognostic analysis of relapsed pediatric acute lymphoblastic leukemia (PubMed, Zhonghua Er Ke Za Zhi)

ETV6::RUNX1 is the most common genetic aberration with a favorable outcome. HSCT could rescue the outcome of relapsed children, though the survival rate is still poor.

1 month ago

Journal

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

Certainty in uncertainty: Determining the rate and reasons for reclassification of variants of uncertain significance in haematological malignancies. (PubMed, EJHaem)

This study on reclassification of VUS in blood cancers demonstrated that one in seven VUS were re-classified 12 months post initial classification. This can inform practice guidelines and potentially impact the prognosis, diagnosis and treatment of haematological malignancies.

1 month ago

Journal

DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CSF3R (Colony Stimulating Factor 3 Receptor) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

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)

Molecular genetic characterization of myeloid neoplasms with idic(X)(q13) and i(X)(q10). (PubMed, Front Oncol)

i(X)(q10) in our study turned out to be a cryptic idic(X)(p11) aberration, reported for the first time here. TET2, SF3B1, ASXL1, or SRSF2 were highly prevalent in patients with idic(X)(q13)/i(X)(q10) abnormalities and were often associated with a worse prognosis.

1 month ago

Journal

TP53 (Tumor protein P53) • 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) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2)

ONC-201 Maintenance Therapy in Acute Myeloid Leukemia and Myelodysplastic Syndrome After Stem Cell Transplant (clinicaltrials.gov)

P1, N=20, Active, not recruiting, University of Nebraska | Trial primary completion date: Aug 2024 --> Oct 2026

1 month ago

Trial primary completion date

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

TP53 mutation • ASXL1 mutation

dordaviprone (ONC201)

Hematologic Cancer after Gene Therapy for Cerebral Adrenoleukodystrophy. (PubMed, N Engl J Med)

Hematologic cancer developed in a subgroup of patients who were treated with eli-cel; the cases are associated with clonal vector insertions within oncogenes and clonal evolution with acquisition of somatic genetic defects. (Funded by Bluebird Bio; ALD-102, ALD-104, and LTF-304 ClinicalTrials.gov numbers, NCT01896102, NCT03852498, and NCT02698579, respectively.).

1 month ago

Journal • Gene therapy

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RUNX1 (RUNX Family Transcription Factor 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • WT1 (WT1 Transcription Factor) • CD34 (CD34 molecule) • MECOM (MDS1 And EVI1 Complex Locus) • PRDM16 (PR/SET Domain 16)

KRAS mutation • NRAS mutation • WT1 mutation

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

Two novel families with RUNX1 variants indicate glycine 168 as a new mutational hotspot: Implications for FPD/AML diagnosis. (PubMed, Br J Haematol)

Although classified as of unknown significance (VUS) by RUNX1-specific curation guidelines, these variants should rather be considered likely pathogenic, as supported by computational tools, structural modelling and dysregulated platelet expression of RUNX1-targets, adding Gly168 among amino acids currently recognised as mutational hotspots. Our data could help reduce the number of variants classified as VUS, providing evidence for updating RUNX1 guidelines, thus improving FPD/AML diagnosis.

1 month ago

Journal

RUNX1 (RUNX Family Transcription Factor 1)

Clinical features and long-term outcomes of pediatric patients with de novo acute myeloid leukemia in China with or without specific gene abnormalities: a cohort study of patients treated with BCH-AML 2005. (PubMed, Hematology)

Not achieving complete remission after induction 2 was found to be an independent prognostic factor for OS and EFS. These findings indicate that genetic abnormalities could be considered stratification factors, predict patient outcomes, and imply the application of targeted therapy.

1 month ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • NUP214 (Nucleoporin 214) • CBFB (Core-Binding Factor Subunit Beta 2) • DEK (DEK Proto-Oncogene)

FLT3-ITD mutation • KIT mutation • KMT2A rearrangement • MLL rearrangement • DEK-NUP214 rearrangement

2ms

Clinicopathological and Molecular Genetic Insights into EBV-Positive Inflammatory Follicular Dendritic Cell Sarcoma. (PubMed, Hum Pathol)

Compared with the FDCS group, EBV+ IFDCS patients had a significantly longer median PFS time (p<0.05). In conclusion, EBV+ IFDCS represents a group of tumors with unique clinical, morphological, immunological, prognostic, and molecular cytogenetic characteristics.

2 months ago

Journal

EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • RUNX1 (RUNX Family Transcription Factor 1) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CXCL13 (Chemokine (C-X-C motif) ligand 13) • MTHFR (Methylenetetrahydrofolate Reductase) • SSTR2 (Somatostatin Receptor 2) • NQO1 (NAD(P)H dehydrogenase, quinone 1) • FANCG (FA Complementation Group G) • CDKN1C (Cyclin Dependent Kinase Inhibitor 1C) • CR1 (Complement C3b/C4b Receptor 1) • FCER2 (Fc Fragment Of IgE Receptor II)

EGFR expression • PDGFRA mutation • MSH2 mutation • MLH1 mutation • STAT3 expression • FANCG mutation

2ms

Advancements in genetic analysis: Insights from a case study and review of next-generation sequencing techniques for veterinary oncology applications. (PubMed, Vet Clin Pathol)

Most importantly, analytical and clinical validation processes are essential to ensure the reliability and clinical utility of NGS-based assays. Overall, integrating NGS technologies into veterinary oncology holds great potential for advancing our understanding of AML and improving disease stratification, in hopes of improving clinical outcomes.

2 months ago

Review • Journal • Next-generation sequencing

KRAS (KRAS proto-oncogene GTPase) • RUNX1 (RUNX Family Transcription Factor 1) • IKZF1 (IKAROS Family Zinc Finger 1)

KRAS mutation

2ms

Epigenomic and transcriptomic profiling of solitary fibrous tumors identifies site-specific patterns and candidate genes regulated by DNA methylation. (PubMed, Lab Invest)

In all analyses, TBX15 methylation and mRNA expression retained the strongest association with tissue of origin in SFT and other sarcomas, suggesting a possible marker to distinguish metastatic tumors from new primaries without genomic profiling. Epigenetic signatures may further help to identify SFT progenitor cells at different anatomic sites.

2 months ago

Journal • Epigenetic controller

EGFR (Epidermal growth factor receptor) • RUNX1 (RUNX Family Transcription Factor 1) • PBX1 (PBX Homeobox 1) • MEIS1 (Meis Homeobox 1) • EBF1 (EBF Transcription Factor 1) • STAT6 (Signal transducer and activator of transcription 6) • TBX1 (T-Box Transcription Factor 1) • NAB2 (NGFI-A Binding Protein 2) • EBF3 (EBF Transcription Factor 3)

2ms

Inherited Predispositions to Myeloid Neoplasms: Pathogenesis and Clinical Implications. (PubMed, Annu Rev Pathol)

Here, we review several disorders from this WHO entity as well as other related conditions with an emphasis on the molecular pathogenesis of disease and accompanying somatic alterations. Finally, we provide an overview of establishing the molecular diagnosis of these germline genetic conditions and general recommendations for screening and management of the associated hematologic conditions.

2 months ago

Review • Journal

2ms

Fludarabine and Cytarabine Versus High-dose Cytarabine for CBF-AML (clinicaltrials.gov)

P4, N=68, Completed, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine | Recruiting --> Completed | N=200 --> 68

2 months ago

Trial completion • Enrollment change

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

cytarabine • fludarabine IV

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

PHF6 mutations in chronic myelomonocytic leukemia identify a unique subset of patients with distinct phenotype and superior prognosis. (PubMed, Am J Hematol)

The specific molecular signatures sustained their significant predictive performance in the context of the CMML-specific molecular prognostic model (CPSS-mol). PHF6MUT identifies a unique subset of patients with CMML characterized by thrombocytopenia, higher prevalence of LoY, and superior prognosis.

2 months ago

Journal

DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • PHF6 (PHD Finger Protein 6)

SRSF2 mutation • U2AF1 mutation • PHF6 mutation

2ms

Activating mutations remodel the chromatin accessibility landscape to drive distinct regulatory networks in KMT2A-rearranged acute leukemia. (PubMed, Hemasphere)

Human KMT2A-r AML cells could be pharmacologically sensitized to NKG2D-CAR T cells by treatment with the histone deacetylase inhibitor LBH589 (panobinostat) which caused upregulation of NKG2D-ligand levels...Finally, the results were validated and extended to acute leukemia in infancy. Combined, activating mutations induced mutation-specific changes in the epigenetic landscape, leading to changes in transcriptional programs orchestrated by specific transcription factor networks.

2 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • STAT5B (Signal Transducer And Activator Of Transcription 5B) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • STAT5A (Signal Transducer And Activator Of Transcription 5A) • NKG2D (killer cell lectin like receptor K1)

RAS mutation • KMT2A rearrangement • MLL rearrangement • NRAS G12D • NRAS G12 • FLT3 N676K • MLL mutation • KMT2A expression

Farydak (panobinostat)