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GENE:

MECOM (MDS1 And EVI1 Complex Locus)

News alerts, weekly reports and conference planners

Genocopy of EVI1-AML with paraneoplastic diabetes insipidus: PRDM16 overexpression by t(1;2)(p36;p21) and enhancer hijacking. (PubMed, Br J Haematol)

The patient was successfully allografted, she is in complete remission 14 months later. We conclude that t(1;2)(p36;p21), with massive PRDM16 overexpression, can result in a faithful genocopy of EVI1/PRDM3/MECOM AML, including DI.

8 days ago

Journal

MECOM (MDS1 And EVI1 Complex Locus) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • PRDM16 (PR/SET Domain 16) • ZFP36 (ZFP36 Ring Finger Protein)

11d

Systematic pan-cancer analysis of the prognostic value of MECOM in human cancer. (PubMed, Discov Oncol)

Furthermore, the mechanism of MECOM-mediated oncogenesis was tentatively explored by immune infiltration analysis. This study provided a relatively comprehensive overview of the prognostic and immunological roles of MECOM in multiple cancers.

11 days ago

Journal • Tumor mutational burden • Pan tumor

TMB (Tumor Mutational Burden) • MECOM (MDS1 And EVI1 Complex Locus)

21d

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.

21 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

21d

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.

21 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

28d

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.

28 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)

MECOM and the PRDM gene family in uterine endometrial cancer: bioinformatics and experimental insights into pathogenesis and therapeutic potentials. (PubMed, Mol Med)

The PRDM gene family, particularly MECOM, plays a crucial role in the pathogenesis and progression of UCEC, suggesting its utility as a target for novel therapeutic interventions. Our findings offer valuable insights for future research and potential clinical application in managing uterine endometrial cancer.

1 month ago

Journal

MECOM (MDS1 And EVI1 Complex Locus) • TGFB1 (Transforming Growth Factor Beta 1)

2ms

MECOM Locus classical transcript isoforms affect tumor immune microenvironment and different targets in ovarian cancer. (PubMed, J Ovarian Res)

Diverse protein isoforms derived from MECOM were found to differentially affect the survival and tumor development in ovarian cancer patients through specific mechanisms. Investigating the molecular mechanisms underlying disease pathogenesis and identifying potential drug target proteins at the level of splice variant isoforms were deemed crucial.

2 months ago

Journal

CD8 (cluster of differentiation 8) • MECOM (MDS1 And EVI1 Complex Locus) • JUN (Jun proto-oncogene)

2ms

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.).

2 months 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

2ms

The role and regulation of EVI1 in normal hematopoiesis and hematopoietic malignancies (PubMed, Rinsho Ketsueki)

While the mechanism by which 3q26 translocation leads to high EVI1 expression through enhancer hijacking of genes active in myeloid development is now better understood, regulation of EVI1 expression in the absence of chromosomal translocations and in normal hematopoiesis remains unclear. Recent studies have provided insight into the regulatory mechanisms of EVI1 expression and action, which may lead to development of targeted therapies in the near future.

2 months ago

Review • Journal

MECOM (MDS1 And EVI1 Complex Locus)

2ms

The microprotein HDSP promotes gastric cancer progression through activating the MECOM-SPINK1-EGFR signaling axis. (PubMed, Nat Commun)

HDSP knockdown inhibits tumor growth in a PDX (patient-derived xenograft) model, and infusion of an artificially synthesized HDSP peptide as a neoantigen enhances immune cell-mediated anti-tumor efficacy against gastric cancer in vitro and in vivo. These findings propose HDSP as a potential therapeutic target or neoantigen candidate for gastric cancer treatment.

2 months ago

Journal

MECOM (MDS1 And EVI1 Complex Locus) • HOXA9 (Homeobox A9) • SPINK1 (Serine peptidase inhibitor, kazal type 1) • HOXA10 (Homeobox A10)

2ms

Germline genetic variants that predispose to myeloproliferative neoplasms and hereditary myeloproliferative phenotypes. (PubMed, Leuk Res)

Knowledge of those genes and germline genetic changes which lead to MPN or diseases that mimic MPN helps to improve accuracy of diagnosis, aids with counselling regarding familial risk, and may contribute to clinical decision-making. Large scale population exome and genome sequencing studies will improve our knowledge of both common and rare germline genetic contributions to MPN.

2 months ago

Review • Journal

ATM (ATM serine/threonine kinase) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • MECOM (MDS1 And EVI1 Complex Locus) • DDX41 (DEAD-Box Helicase 41) • SH2B3 (SH2B Adaptor Protein 3)

2ms

Retraction: Myeloid ecotropic viral integration site 1 inhibits cell proliferation, invasion or migration in human gastric cancer. (PubMed, Oncotarget)

No abstract available

2 months ago

Journal

MECOM (MDS1 And EVI1 Complex Locus)

3ms

Modelling and drug targeting of a myeloid neoplasm with atypical 3q26/MECOM rearrangement using patient-specific iPSCs. (PubMed, Br J Haematol)

Furthermore, we revealed the apoptotic effects of the bromodomain and extra-terminal motif (BET) inhibitor on iPSC-derived MDS cells by suppressing activated MECOM. Our study demonstrates the usefulness of iPSC models for uncovering the precise mechanism of enhancer hijacking due to chromosomal structural changes and discovering potential therapeutic drug candidates for cancer treatment.

3 months ago

Journal

MECOM (MDS1 And EVI1 Complex Locus)

4ms

Off-the-shelf NK Cells + SCT for Myeloid Malignancies (clinicaltrials.gov)

P1/2, N=24, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2024 --> Jun 2026 | Trial primary completion date: Jun 2024 --> Jun 2026

4 months ago

Trial completion date • Trial primary completion date • Combination therapy

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • MECOM (MDS1 And EVI1 Complex Locus) • NUP214 (Nucleoporin 214) • GATA2 (GATA Binding Protein 2) • DEK (DEK Proto-Oncogene)

cyclophosphamide • melphalan • fludarabine IV • mesna • Neupogen (filgrastim)

4ms

Genomic alterations in two patients with esophageal carcinosarcoma identified by whole genome sequencing: a case report. (PubMed, Surg Case Rep)

Our findings indicate that therapeutic drugs targeting the activation signal or FA pathway might be effective in treating ECS, however, their therapeutic significance should be elucidated in future studies.

4 months ago

Journal

TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • CCND1 (Cyclin D1) • MECOM (MDS1 And EVI1 Complex Locus) • RAC1 (Rac Family Small GTPase 1) • FANCI (FA Complementation Group I) • APOB (Apolipoprotein B) • FANCG (FA Complementation Group G)

4ms

A novel FNDC3B::MECOM fusion gene accompanied with Der(5; 17)(p10; q10) in acute myelocytic leukemia. (PubMed, Ann Hematol)

No abstract available

4 months ago

Journal

MECOM (MDS1 And EVI1 Complex Locus)

5ms

Optical genome mapping improves the accuracy of classification, risk stratification, and personalized treatment strategies for patients with acute myeloid leukemia. (PubMed, Am J Hematol)

Overall, 24 (15%) aberrations were identified exclusively by OGM and had the potential to alter AML classification, risk stratification, and/or clinical trial eligibility. OGM emerges as a powerful tool for identifying fusion genes and detecting subtle or cryptic cytogenomic aberrations that may otherwise remain undetectable by CBA.

5 months ago

Journal

JAK2 (Janus kinase 2) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • MECOM (MDS1 And EVI1 Complex Locus)

5ms

CRISPR-Cas9-mediated deletion enhancer of MECOM play a tumor suppressor role in ovarian cancer. (PubMed, Funct Integr Genomics)

This study demonstrates that JQ-1 can inhibit the expression of MECOM and tumorigenesis. Deletion of the enhancer activity of MECOM has an indispensable role in inhibiting ovarian cancer progress, which sheds light on a promising opportunity for ovarian cancer treatment through the application of this non-coding DNA deletion.

5 months ago

Journal

MECOM (MDS1 And EVI1 Complex Locus)

JQ-1

5ms

Acute myeloid leukemia (AML) with chromosome 3 inversion: biology, management, and clinical outcome. (PubMed, Leuk Lymphoma)

Current treatment modalities, including intensive chemotherapy (IC), hypomethylating agents (HMAs) combined with venetoclax, and allogeneic stem cell transplantation are discussed, highlighting outcomes achieved and their limitations...The poor prognosis associated with inv(3) AML underscores the urgent need to develop more potent therapies for this AML subtype. This comprehensive overview aims to contribute to a deeper understanding of inv(3) AML and guide future research and treatment strategies.

5 months ago

Clinical data • Review • Journal

MECOM (MDS1 And EVI1 Complex Locus) • GATA2 (GATA Binding Protein 2)

Venclexta (venetoclax)

6ms

Orthogonal proteogenomic analysis identifies the druggable PA2G4-MYC axis in 3q26 AML. (PubMed, Nat Commun)

PA2G4 overexpression rescues AML cells from the inhibitory effects of HDACis, while genetic and small molecule inhibition of PA2G4 abrogates EVI1 in 3q26 AML cells, including in patient-derived leukemia xenografts. This study positions PA2G4 at the crosstalk of the EVI1 leukemogenic signal for developing new therapeutics and urges the use of HDACis-based combination therapies in patients with 3q26 AML.

6 months ago

Journal

MECOM (MDS1 And EVI1 Complex Locus)

6ms

Evaluation of European LeukemiaNet 2022 risk classification in patients undergoing allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia: Identification of a very poor prognosis genetic group. (PubMed, Br J Haematol)

Notably, within this analysis, the outcome of Adv and intermediate patients were similar. These findings highlight the prognostic value of ELN 2022 in patients undergoing allo-HCT, which can be improved by the recognition of a poor genetic subset (AdvP) within the Adv risk group.

6 months ago

Journal

TP53 (Tumor protein P53) • MECOM (MDS1 And EVI1 Complex Locus)

7ms

Oncogene EVI1 drives acute myeloid leukemia via a targetable interaction with CTBP2. (PubMed, Sci Adv)

This proof-of-concept study opens the possibility to target one of the most incurable forms of AML with specific EVI1-CTBP inhibitors. This has important implications for other tumor types with aberrant expression of EVI1 and for cancers transformed by different CTBP-dependent oncogenic transcription factors.

7 months ago

Journal

MECOM (MDS1 And EVI1 Complex Locus) • CTBP2 (C-Terminal Binding Protein 2) • CTBP1 (C-Terminal Binding Protein 1)

MECOM rearrangement

7ms

Outcome of 3q26.2/MECOM rearrangements in chronic myeloid leukemia. (PubMed, Int J Hematol)

Outcomes of 3q26.2/MECOM-rearranged CML are poor despite the availability of multiple BCR::ABL1 tyrosine kinase inhibitors (TKIs). Third-generation TKIs in combination with novel agents and possible allo-SCT could be considered given the poor outcomes and resistance to second-generation TKIs.

7 months ago

Journal

ABL1 (ABL proto-oncogene 1) • MECOM (MDS1 And EVI1 Complex Locus)

MECOM rearrangement

7ms

Aberrant ecotropic viral integration site-1 (EVI-1) and myocyte enhancer factor 2 C gene (MEF2C) in adult acute myeloid leukemia are associated with adverse t (9:22) & 11q23 rearrangements. (PubMed, Ann Hematol)

In conclusion, EVI1 & MEF2C were significantly expressed in AML cases. EVI1 & MEF2C overexpression were significantly associated with 11q23 rearrangements and t (9;22) and were indicators for poor outcome in adult AML patients; These results could be a step towards personalized therapy in those patients.

7 months ago

Journal

MECOM (MDS1 And EVI1 Complex Locus) • MEF2C (Myocyte Enhancer Factor 2C)

MEF2C overexpression

7ms

A liquid biopsy assay for the noninvasive detection of lymph node metastases in T1 lung adenocarcinoma. (PubMed, Thorac Cancer)

We have established a new risk prediction model using serum samples from T1 LUAD patients, enabling noninvasive identification of those with positive lymph node metastases.

7 months ago

Journal • Liquid biopsy • Biopsy

MECOM (MDS1 And EVI1 Complex Locus) • CXCL13 (Chemokine (C-X-C motif) ligand 13) • COL1A1 (Collagen Type I Alpha 1 Chain) • FOXC1 (Forkhead Box C1) • PODXL (Podocalyxin) • COL11A1 (Collagen Type XI Alpha 1 Chain)

7ms

(Sialyl)Lewis antigen expression on glycosphingolipids, N- and O-glycans in colorectal cancer cell lines is linked to a colon-like differentiation program. (PubMed, Mol Cell Proteomics)

This indicates a possible role of these TFs in the upregulation of (sialyl)Lewis antigens, particularly on GSL glycans, via FUT3/4 expression in colon-like cell lines. In conclusion, our study provides insights into the possible regulation of glycans in CRC and can serve as a guide for the development of diagnostic and therapeutic biomarkers.

7 months ago

Preclinical • Journal

MECOM (MDS1 And EVI1 Complex Locus) • FUT3 (Fucosyltransferase 3)

7ms

High throughput screening aids clinical decision-making in refractory acute myeloid leukaemia. (PubMed, Cancer Rep (Hoboken))

This case report demonstrates the feasibility and role of combination pre-clinical high throughput screening to aid decision making in high-risk leukaemia. It also demonstrates the role a JAK1/2 inhibitor can have in the palliative setting in select patients with AML.

7 months ago

Journal

ETV6 (ETS Variant Transcription Factor 6) • MECOM (MDS1 And EVI1 Complex Locus)

Jakafi (ruxolitinib) • hydroxyurea

8ms

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

8 months ago

Trial completion date • Trial primary completion date

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

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

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

9ms

MECOM: a bioinformatics and experimentally identified marker for the diagnosis and prognosis of lung adenocarcinoma. (PubMed, Biomark Med)

The ROC curve showed that the area under the curve of MECOM was 0.804 for LUAD and, of note, could reach 0.889 for advanced LUAD; specificity was up to 90%. MECOM may contribute to independently identifying LUAD patients, particularly in advanced stages.

9 months ago

Journal

MECOM (MDS1 And EVI1 Complex Locus)

9ms

The ETV6-MECOM fusion protein promotes EMT-related properties by repressing the transactivation activity of E-cadherin promoter in K562 leukemia cells. (PubMed, Biochem Biophys Rep)

ETV6-MECOM induces EMT-related properties by downregulating the transcriptional expression of E-cadherin and repressing its transactivation activity by binding to its core motif -1116TTAAAA-1111 in leukemia K562 cells. These findings could contribute to the development of a therapeutic target for patients with myeloid leukemia characterized by ETV6-MECOM.

9 months ago

Journal

ETV6 (ETS Variant Transcription Factor 6) • CDH1 (Cadherin 1) • MECOM (MDS1 And EVI1 Complex Locus) • SNAI2 (Snail Family Transcriptional Repressor 2) • ZEB2 (Zinc Finger E-Box Binding Homeobox 2)

CDH1 expression • CDH1 mutation • CDH1 overexpression

10ms

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.

10 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

10ms

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

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

10 months ago

Trial completion date • Trial primary completion date • Combination therapy

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

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

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

11ms

Novel Approaches to Target MECOM/EVI1 in AML (clinicaltrials.gov)

P=N/A, N=24, Recruiting, Gruppo Italiano Malattie EMatologiche dell'Adulto | Not yet recruiting --> Recruiting | Trial completion date: Sep 2026 --> Dec 2026 | Initiation date: Sep 2023 --> Dec 2023 | Trial primary completion date: Sep 2026 --> Dec 2026

11 months ago

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date

MECOM (MDS1 And EVI1 Complex Locus)

12ms

Preclinical efficacy of targeting epigenetic mechanisms in AML with 3q26 lesions and EVI1 overexpression. (PubMed, Leukemia)

Tegavivint (TV, BC-2059), known to disrupt the binding of nuclear β-catenin and TCF7L2/LEF1 with TBL1, also inhibited co-localization of EVI1 with TBL1 and dose-dependently induced apoptosis in AML cell lines and patient-derived (PD) AML cells with 3q26.2 lesions. TV treatment repressed EVI1, attenuated enhancer activity at ERG, TCF7L2, GATA2 and MECOM loci, abolished interactions between MYC enhancers, repressing AML stemness while upregulating mRNA gene-sets of interferon/inflammatory response, TGF-β signaling and apoptosis-regulation. Co-treatment with TV and BETi or venetoclax induced synergistic in vitro lethality and reduced AML burden, improving survival of NSG mice harboring xenografts of AML with 3q26.2 lesions.

12 months ago

Preclinical • Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MCL1 (Myeloid cell leukemia 1) • CDK4 (Cyclin-dependent kinase 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • MECOM (MDS1 And EVI1 Complex Locus) • GATA2 (GATA Binding Protein 2) • TCF7L2 (Transcription Factor 7 Like 2) • TGFB1 (Transforming Growth Factor Beta 1) • BRD4 (Bromodomain Containing 4)

Venclexta (venetoclax) • tegavivint (BC2059)

1year

Hidac Consolidation Cycles May Impede Stem Cell Transplant Planning for High-Risk Acute Myeloid Leukemia Patients (ASH 2023)

The logistics of proceeding to transplant might necessitate consolidation chemotherapy usually involving high dose cytarabine (HiDAC)...Infections included bacteremia from Klebsiella, E. Coli, Proteus, group B strep, vancomycin resistant E. Faecalis, and coagulase negative staph, pneumonia from Klebsiella, urinary tract infections from extended spectrum beta-lactamase resistant E. Coli, Klebsiella, and proteus mirabilis, fungal sinusitis, and Clostridium difficile colitis...HSCT is the sole curative option for high-risk AML patients, and the concept of bridging the period between induction and HSCT with HiDAC consolidation appears to offer no additional benefit compared to IDAC. Moreover, this approach prevents a subset of this population from being fit enough to receive HSCT.

1 year ago

Clinical

TP53 mutation • FLT3-ITD mutation • NPM1 mutation • RUNX1 mutation • ASXL1 mutation • KMT2A rearrangement • MLL rearrangement • FLT3 wild-type • ABL1 deletion

cytarabine

1year

The urothelial gene regulatory network: understanding biology to improve bladder cancer management. (PubMed, Oncogene)

We uncover a TF network involved in urothelial cell identity and BLCA. We identify novel candidate TFs involved in differentiation and cancer that provide opportunities for a better understanding of the underlying biology and therapeutic intervention.

1 year ago

Review • Journal

MECOM (MDS1 And EVI1 Complex Locus) • FOXA1 (Forkhead Box A1) • PPARG (Peroxisome Proliferator Activated Receptor Gamma) • TP63 (Tumor protein 63) • GATA3 (GATA binding protein 3) • TFAP2A (Transcription Factor AP-2 Alpha)

1year

Copy number variants landscape of multiple cancers and clinical applications based on NGS gene panel. (PubMed, Ann Med)

The 16 common CNVs between cancers can be used to identify the target of pan-cancer drug design and targeted therapies. Additionally, 22 caner-specific CNVs can be used as unique diagnostic markers for each cancer type.

1 year ago

Journal • PARP Biomarker • Next-generation sequencing

HER-2 (Human epidermal growth factor receptor 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • KEAP1 (Kelch Like ECH Associated Protein 1) • TOP2A (DNA topoisomerase 2-alpha) • FLT1 (Fms-related tyrosine kinase 1) • MECOM (MDS1 And EVI1 Complex Locus) • FOXA1 (Forkhead Box A1) • EPHB1 (EPH Receptor B1) • NFKBIA (NFKB Inhibitor Alpha 2) • HEY1 (Hes Related Family BHLH Transcription Factor With YRPW Motif 1) • PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3)

Onco PanScan™

1year

GENE FUSIONS ARE A PUTATIVE MECHANISM THAT DIMINISHES SENSITIVITY TO VENETOCLAX-HYPOMETHYLATING AGENTS COMBINATION IN ACUTE MYELOID LEUKEMIA (SIE 2023)

Appealing patterns of resistance emerged from genomic analysis: the â€œactivating likeâ€� signature may help define a specific target among tyrosine kinase inhibitors, while â€œself-renewal likeâ€� patients may benefit from histone deacetylase inhibitors (as we previously published). HOXA genes overexpression open a novel therapeutic options for selected patients.

1 year ago

FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR1 (Fibroblast growth factor receptor 1) • JAK2 (Janus kinase 2) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • ETV6 (ETS Variant Transcription Factor 6) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • CSF3R (Colony Stimulating Factor 3 Receptor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • MECOM (MDS1 And EVI1 Complex Locus) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • BAX (BCL2-associated X protein) • LTBP1 (Latent-transforming growth factor beta-binding protein 1) • CCND2 (Cyclin D2) • DDX5 (DEAD-Box Helicase 5) • BCL11B (BAF Chromatin Remodeling Complex Subunit BCL11B) • PER1 (Period Circadian Clock 1) • TBL1XR1 (TBL1X Receptor 1)

NRAS mutation • CBL mutation • MECOM rearrangement • PDGFRB mutation

TruSight RNA Pan-Cancer Panel

Venclexta (venetoclax)

1year

A primary pediatric acute myelomonocytic leukemia with t(3;21)(q26;q22): A case report. (PubMed, Medicine (Baltimore))

The patient recovered well after Allo-HSCT. Therefore, for patients with RUNX1-MECOM and RUNX1-RPL22 fusion genes, transplantation may be a good choice when chemotherapy is not effective.

1 year ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • MECOM (MDS1 And EVI1 Complex Locus) • RPL22 (Ribosomal Protein L22)

1year

Phase 1 Results of Bromodomain and Extraterminal Inhibitor PLX51107 in Combination with Azacitidine in Patients with Relapsed/Refractory Myeloid Malignancies. (PubMed, Clin Cancer Res)

In a heavily pre-treated patient cohort with R/R MDS and AML, PLX51107+ azacitidine was well-tolerated and resulted in modest clinical benefit.

1 year ago

P1 data • Journal • Combination therapy • IO biomarker

TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • CDK6 (Cyclin-dependent kinase 6) • IL7R (Interleukin 7 Receptor) • MECOM (MDS1 And EVI1 Complex Locus) • BRD4 (Bromodomain Containing 4) • CD93 (CD93 Molecule) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • HEXIM1 (HEXIM P-TEFb Complex Subunit 1)

TP53 mutation • MYC expression

Venclexta (venetoclax) • azacitidine • PLX51107