News - ASXL1 mutation

Chronic neutrophilic leukemia and atypical chronic myeloid leukemia: 2024 update on diagnosis, genetics, risk stratification, and management. (PubMed, Am J Hematol)

Most commonly used agents include hydroxyurea, interferon, Janus kinase inhibitors, and hypomethylating agents, though none are disease-modifying. Actionable mutations (NRAS/KRAS, ETNK1) have also been identified, supporting novel agents targeting involved pathways. Preclinical and clinical studies evaluating new drugs (e.g., fedratinib, phase 2) and combinations are detailed.

4 days ago

Review • Journal

KRAS (KRAS proto-oncogene GTPase) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • 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) • ETNK1 (Ethanolamine Kinase 1)

KRAS mutation • NRAS mutation • ASXL1 mutation • TET2 mutation • EZH2 mutation • SRSF2 mutation • U2AF1 mutation • CSF3R T618I • CSF3R mutation • ETNK1 mutation

hydroxyurea • Inrebic (fedratinib)

Analysis of CSF3R mutations in atypical chronic myeloid leukemia and other myeloid malignancies. (PubMed, Ann Diagn Pathol)

In conclusion, CSF3R mutations were found at a higher frequency in aCML patients than in previous studies, which might reflect ethnic differences. Additional studies are needed to confirm these findings and the relationship between CSF3R and CEBPA mutations.

6 days ago

Journal

ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • CSF3R (Colony Stimulating Factor 3 Receptor) • CEBPA (CCAAT Enhancer Binding Protein Alpha)

ASXL1 mutation • SRSF2 mutation • CEBPA mutation • CSF3R T618I • CSF3R mutation

Clinical laboratory characteristics and gene mutation spectrum of Ph-negative MPN patients with atypical variants of JAK2, MPL, or CALR. (PubMed, Cancer Med)

These data indicate that classical mutations of JAK2, MPL, and CALR may not be completely mutually exclusive with atypical variants of JAK2, MPL, and CALR. In this study, 30 different atypical variants of JAK2, MPL, and CALR were identified, JAK2 G127D being the most common (42%, 23/55). Interestingly, JAK2 G127D only co-occurred with JAK2V617F mutation. The incidence of atypical variants of JAK2 in Ph-negative MPNs was much higher than that of the atypical variants of MPL and CALR. The significance of these atypical variants will be further studied in the future.

7 days ago

Journal

JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • CALR (Calreticulin) • SH2B3 (SH2B Adaptor Protein 3)

ASXL1 mutation • JAK2 V617F

14d

Clonal Hematopoiesis and Inflammation in the VasculaturE (CHIVE): a prospective, longitudinal cohort and biorepository. (PubMed, Blood Adv)

Surprisingly, ~30% of patients enrolled in CHIVE from CH clinics were adjudicated as not having CHIP, highlighting the need for molecular standards and purpose-built assays in this field. Maintenance of this well-annotated cohort and continued expansion of CHIVE to multiple institutions is underway and will be critical to understand how to thoughtfully care for this patient population.

14 days ago

Journal

TP53 (Tumor protein P53) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2)

ASXL1 mutation

18d

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

18 days ago

Trial completion date • Trial primary completion date

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

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

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

27d

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

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

27 days ago

Journal

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

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

27d

Blastic plasmacytoid dendritic cell tumor treated with DVT regimen: a case report and literature review (PubMed, Zhonghua Xue Ye Xue Za Zhi)

The patient with skin nodules and the pathology diagnosed BPDCN, the next generation sequencing of skin nodules showed mutations of IDH2 and ASXL1. DVT (decitabine combined with Venetoclax and thalidomide) has significant efficacy with rapid and deep remission for BPDCN, and the adverse effects is less, especially suitable for elderly patients who cannot tolerate intense chemotherapy.

27 days ago

Review • Journal

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ASXL1 (ASXL Transcriptional Regulator 1)

IDH2 mutation • ASXL1 mutation

Venclexta (venetoclax) • decitabine • thalidomide

29d

Triple-Negative Myelofibrosis: Disease Features, Response to Treatment and Outcomes. (PubMed, Clin Lymphoma Myeloma Leuk)

TN-MF is invariably associated with significantly decreased survival and more aggressive clinical behavior with higher rates of leukemic transformation and shorter duration of response to ruxolitinib. Mutations impacting RNA splicing, epigenetic modification and signaling (SRSF2, SETBP1, IDH2, CBL, and GNAS) are more common in TN-MF, which likely drive its aggressive course and may account for suboptimal responses to JAK inhibition.

29 days ago

Journal

ABL1 (ABL proto-oncogene 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • SETBP1 (SET Binding Protein 1) • GNAS (GNAS Complex Locus) • CALR (Calreticulin)

ASXL1 mutation • SRSF2 mutation • LDH-L

Jakafi (ruxolitinib)

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

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

1 month ago

Journal • Real-world evidence • Real-world

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

DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • TET2 mutation

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

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

1 month ago

Journal

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

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

Cancer patients with clonal hematopoiesis die from primary malignancy or comorbidities despite higher rates of transformation to myeloid neoplasms. (PubMed, Cancer Med)

In a population including mostly cancer patients, CH was associated with comorbidities and myeloid transformation in patients with higher mutational burdens and anemia. Nevertheless, such patients were less likely to die of their myeloid neoplasm than of primary malignancy or comorbidities.

1 month ago

Journal • Tumor mutational burden

TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2)

TMB-H • ASXL1 mutation

2ms

Therapeutic Targeting of TIM-4-L With Engineered T Cells for Acute Myeloid Leukemia. (PubMed, Clin Cancer Res)

These results highlight TIM-4-L as a highly prevalent target on AML across a range of genetic classifications and novel target for T cell-based therapy in AML. Further investigations into the role of TIM-4-L in AML pathogenesis and its potential as an anti-leukemic target for clinical development are warranted.

2 months ago

Journal

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

TP53 mutation • ASXL1 mutation

2ms

Chronic myelomonocytic leukemia: 2024 update on diagnosis, risk stratification and management. (PubMed, Am J Hematol)

Drug therapy is currently not disease-modifying and includes hydroxyurea and hypomethylating agents; a recent phase-3 study (DACOTA) comparing hydroxyurea and decitabine, in high-risk MP-CMML, showed similar overall survival at 23.1 versus 18.4 months, respectively, despite response rates being higher for decitabine (56% vs. 31%). These include systemic inflammatory autoimmune diseases, leukemia cutis and lysozyme-induced nephropathy; the latter requires close monitoring of renal function during leukocytosis and is a potential indication for cytoreductive therapy.

2 months ago

Journal

DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2)

DNMT3A mutation • ASXL1 mutation • TET2 mutation • SRSF2 mutation

decitabine • hydroxyurea

2ms

Sex and race-dependent variations in the mutational landscape of clonal hematopoiesis (AACR 2024)

Our analysis provides insights into the complex interplay of sex and racial factors in shaping CHIP mutation frequencies. As CHIP continues to gain recognition as a critical precursor to malignancies, understanding these variations contributes to refining our understanding of its underlying mechanisms and clinical implications.

2 months ago

IO biomarker

DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • AURKA (Aurora kinase A) • STAT5B (Signal Transducer And Activator Of Transcription 5B) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor) • CSF1R (Colony stimulating factor 1 receptor) • SOX17 (SRY-Box Transcription Factor 17) • ELF3 (E74 Like ETS Transcription Factor 3) • CDKN1B (Cyclin dependent kinase inhibitor 1B) • CENPA (Centromere protein A) • EIF1AX (Eukaryotic Translation Initiation Factor 1A X-Linked) • H3C1 (H3 Clustered Histone 1) • SMAD2 (SMAD Family Member 2)

DNMT3A mutation • ASXL1 mutation

MSK-IMPACT

2ms

A comprehensive genomic profiling of myeloid malignancies demonstrates mutational spectrum of DNA variants, FLT3-ITDs, and gene fusions (AACR 2024)

The Oncomine Myeloid Assay is a fast, robust, and reproducible solution for comprehensive genomic profiling of myeloid malignancies. We describe the mutational spectrum of DNA variants and RNA fusions in a range of clinical research samples. (For research use only.

2 months ago

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR1 (Fibroblast growth factor receptor 1) • DNMT3A (DNA methyltransferase 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • CREBBP (CREB binding protein) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • ZMYM2 (Zinc Finger MYM-Type Containing 2) • CALR (Calreticulin) • KAT6A (Lysine Acetyltransferase 6A) • ANKRD26 (Ankyrin Repeat Domain Containing 26)

FLT3-ITD mutation • ASXL1 mutation • TET2 mutation • SRSF2 mutation • FGFR1 fusion

Oncomine Myeloid Assay GX • Oncomine Myeloid Research Assay

2ms

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

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

2 months ago

Journal

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

RUNX1 mutation • ASXL1 mutation • U2AF1 mutation • PHF6 mutation

2ms

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

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

2 months ago

Trial completion date • Trial primary completion date

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

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

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

2ms

Analysis of CHIP-Related Mutation and Risk of Cardio-Cerebrovasculars Events in Patients with Myeloproliferative Neoplasms (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)

There is a higher mutation rate of CHIP-related genes in MPN patients, especially those over 60 years old. Older age, thrombosis history, CHIP-related mutations and IL-1β elevated levels are independent risk factors for CCEs in MPN. DNMT3A and ASXL1 mutations are independent risk factors for CCEs in PV patients. CHIP-related gene mutations and inflammatory cytokine IL-1 β elevated levels may be the novel risk factors for CCEs in MPN.

2 months ago

Journal

TP53 (Tumor protein P53) • DNMT3A (DNA methyltransferase 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) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D) • IL1B (Interleukin 1, beta)

DNMT3A mutation • ASXL1 mutation • JAK2 V617F • PPM1D mutation • DNMT3A mutation + ASXL1 mutation

2ms

The Correlation of Gene Mutation and Clinical Characteristics in Patients with Myelodysplastic Syndrome and Prognostic Analysis (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)

Gene mutation is closely related to cytogenetic indexes and clinical features (peripheral blood cell count, sex, age). IPSS-R prognostic score and TP53 were risk factors affecting OS in MDS patients.

2 months ago

Journal

TP53 (Tumor protein P53) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • WT1 (WT1 Transcription Factor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • SETBP1 (SET Binding Protein 1)

TP53 mutation • TP53 wild-type • ASXL1 mutation • SF3B1 mutation • U2AF1 mutation

2ms

Clinical Significance of Genetic and Molecular Changes in Primary Myeloid Sarcoma (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)

The genetic and molecular abnormalities of primary MS can be detected by FISH and NGS techniques. FLT3-ITD, RUNX1, ASXL1 or TP53 mutation indicates a worse prognosis, but further clinical studies are needed to confirm it.

2 months ago

Journal

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • RARA (Retinoic Acid Receptor Alpha) • PML (Promyelocytic Leukemia) • CD34 (CD34 molecule) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • CD68 (CD68 Molecule) • CBFB (Core-Binding Factor Subunit Beta 2) • CD99 (CD99 Molecule) • SPN (Sialophorin)

TP53 mutation • FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • KIT mutation • ASXL1 mutation • CEBPA mutation

2ms

A predictive classifier of poor prognosis in transplanted patients with juvenile myelomonocytic leukemia: a study on behalf of the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire. (PubMed, Haematologica)

By integrating genetic information with clinical and hematological features, we have devised a predictive classifier. This classifier effectively identifies a subgroup of patients who are at a heightened risk of unfavorable post-transplant outcomes who would benefit novel therapeutic agents and post-transplant strategies.

2 months ago

Journal

ASXL1 (ASXL Transcriptional Regulator 1) • JAK3 (Janus Kinase 3) • SETBP1 (SET Binding Protein 1)

RAS mutation • ASXL1 mutation • JAK3 mutation

2ms

Human ASXL1-mutant hematopoiesis is driven by a truncated protein associated with aberrant de-ubiquitination of H2AK119. (PubMed, Blood Cancer Discov)

We demonstrate that mutations in ASXL1 lead to the expression of a functional, truncated protein and determine that truncated ASXL1 leads to global redistribution of the repressive chromatin mark H2AK119Ub, increased transposase-accessible chromatin, and activation of both myeloid and stem cell gene expression programs. Finally, we demonstrate that H2AK119Ub levels are tied to truncated ASXL1 expression levels and leverage this observation to demonstrate that inhibition of the PRC1 complex might be an ASXL1-mutant specific therapeutic vulnerability both in pre-malignant CH and myeloid malignancy.

2 months ago

Journal

ASXL1 (ASXL Transcriptional Regulator 1)

ASXL1 mutation

2ms

IMPACT OF CO-MUTATIONS ON THE TRANSPLANT OUTCOMES IN AML PATIENTS WITH DNMT3A MUTATION (EBMT 2024)

Notably, none of the patients received oral azacitidine as maintenance therapy... The results indicated that NPM1-/FLT3-ITD- and NPM1+/FLT3-ITD- subgroups in DNMT3A mutated AML benefit from allo-HSCT in CR1. Larger cohorts are warranted to validate these findings.

2 months ago

Clinical

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) • ASXL1 (ASXL Transcriptional Regulator 1)

FLT3-ITD mutation • IDH2 mutation • NPM1 mutation • DNMT3A mutation • ASXL1 mutation

TruSight Myeloid Sequencing Panel

Onureg (azacitidine oral)

2ms

IMPACT OF CO-MUTATIONS ON THE TRANSPLANT OUTCOMES IN AML PATIENTS WITH DNMT3A MUTATION (EBMT 2024)

2 months ago

Clinical

FLT3-ITD mutation • IDH2 mutation • NPM1 mutation • DNMT3A mutation • ASXL1 mutation

TruSight Myeloid Sequencing Panel

Onureg (azacitidine oral)

3ms

Altered erythropoiesis via JAK2 and ASXL1 mutations in myeloproliferative neoplasms. (PubMed, Exp Hematol)

Lastly, treatment of CD34+ hematopoietic/stem progenitor cells with PRMT6 inhibitor, EPZ020411 induced expression of genes involved in heme metabolism, hemoglobin, and erythropoiesis. These findings highlight interactions between JAK2 and ASXL1 mutations and a unique erythroid regulatory network in the context of mutant ASXL1.

3 months ago

Journal

JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • CD34 (CD34 molecule) • TFRC

ASXL1 mutation • JAK2 mutation

3ms

This hypothesis has been explored in clinical trials data where the presence of CH in ER+ and HER2+ metastatic BC patient cohorts (MSK-IMPACT) was associated with the response to first line CDK4/6i/endocrine therapy or taxol/herceptin/pertuzumab, respectively. We also tested whether CH can accelerate dormant DCC awakening in a murine model of CH carrying mutations in DNMT3A (KO or point mutation) and HER2+ mammary cancer. We propose our work may provide unprecedented insights into how a traceable age-related-mosaicism in the bone marrow (CH) may shape distant organs to be drive metastatic relapse.

3 months ago

HER-2 (Human epidermal growth factor receptor 2) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CDK4 (Cyclin-dependent kinase 4)

HER-2 mutation • DNMT3A mutation • ASXL1 mutation • TET2 mutation

MSK-IMPACT

Herceptin (trastuzumab) • paclitaxel • Perjeta (pertuzumab)

3ms

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

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

3 months ago

Trial completion date • Trial primary completion date • Combination therapy

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

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

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

3ms

Genomic classification and outcomes of young patients with polycythemia vera and essential thrombocythemia according to the presence of splanchnic vein thrombosis and its chronology. (PubMed, Ann Hematol)

In conclusion, clinical and molecular characteristics are different in PV/ET patients with SVT, depending on whether it occurs at diagnosis or at follow-up. Molecular characterization by NGS is useful for assessing the risk of thrombosis and disease progression in young patients with PV/ET.

3 months ago

Journal

DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2)

DNMT3A mutation • ASXL1 mutation • TET2 mutation • JAK2 mutation

3ms

Analysis of gene mutation characteristics and its correlation with prognosis in patients with myelodysplastic syndromes. (PubMed, Clin Chim Acta)

Additionally, the study developed a risk score based on gene mutation data that demonstrated robust predictive capability and stability for the overall survival of MDS patients. Our research provided a strong theoretical basis for the establishment of personalized treatment and prognostic risk assessment models for Chinese MDS patients.

3 months ago

Journal

TP53 (Tumor protein P53) • DNMT3A (DNA methyltransferase 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • ETV6 (ETS Variant Transcription Factor 6) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)

TP53 mutation • DNMT3A mutation • ASXL1 mutation • SF3B1 mutation • U2AF1 mutation • ETV6 mutation

3ms

Multiple Genomic Alterations, Including a Novel AFF4::IRF1 Fusion Gene, in a Treatment-Refractory Blastic Plasmacytoid Dendritic-Cell Neoplasm: A Case Report and Literature Review. (PubMed, Int J Mol Sci)

The patient showed resistance to Tagraxofusp and Venetoclax, and he died about 16 months after diagnosis. Considering the predicted effect of the AFF4::IRF1 fusion on IRF1's antitumor effects and immune regulation, and the possibility of its relevance to the aggressive course observed in this case, we propose further evaluation of the clinical significance of this fusion in BPDCN in future cooperative group studies and the consideration of therapeutic strategies aimed at restoring IRF1-dependent antineoplastic effects in such cases.

3 months ago

Clinical • Review • Journal

MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • AFF4 (AF4/FMR2 Family Member 4) • IRF1 (Interferon Regulatory Factor 1)

ASXL1 mutation • TET2 mutation • IRF1 expression

Venclexta (venetoclax) • Elzonris (tagraxofusp-erzs)

3ms

Artificial intelligence-based prediction models for acute myeloid leukemia using real-life data: A DATAML registry study. (PubMed, Leuk Res)

We designed artificial intelligence-based prediction models (AIPM) using 52 diagnostic variables from 3687 patients included in the DATAML registry treated with intensive chemotherapy (IC, N = 3030) or azacitidine (AZA, N = 657) for an acute myeloid leukemia (AML)...We believe that AIPM could help hematologists to deal with the huge amount of data available at diagnosis, enabling them to have an OS estimation and guide their treatment choice. Our registry-based AIPM could offer a large real-life dataset with original and exhaustive features and select a low number of diagnostic features with an equivalent accuracy of prediction, more appropriate to routine practice.

3 months ago

Journal

KIT (KIT proto-oncogene, receptor tyrosine kinase) • NPM1 (Nucleophosmin 1) • ASXL1 (ASXL Transcriptional Regulator 1) • NCAM1 (Neural cell adhesion molecule 1) • ANPEP (Alanyl Aminopeptidase, Membrane) • MPO (Myeloperoxidase)

NPM1 mutation • ASXL1 mutation • KIT expression • NPM1 expression

azacitidine

4ms

Droplet digital PCR for sensitive relapse detection in acute myeloid leukaemia patients transplanted by reduced intensity conditioning. (PubMed, Eur J Haematol)

These results confirm that qPCR targeting NPM1 mutations or fusion transcripts are superior in MRD testing. In the absence of such targets, ddPCR is a promising alternative demonstrating (a) high applicability, (b) high sensitivity, and (c) zero false positive MRD relapses in non-relapsing patients.

4 months ago

Journal

NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • WT1 (WT1 Transcription Factor)

NPM1 mutation • DNMT3A mutation • ASXL1 mutation • TET2 mutation • WT1 overexpression

4ms

The Role of ASXL1 Mutations And ASXL1CircRNAs In Cancer. (PubMed, Biomarkers)

This study aimed to review the ASXL1 and the ASXL1CircRNAs roles, such as epigenetics regulation, chromatin modification, and transcription factor function in malignancies. At last, their role in metastasis and survival was summarized.

4 months ago

Review • Journal

ASXL1 (ASXL Transcriptional Regulator 1)

ASXL1 mutation

4ms

DNMT3A/TET2/ASXL1 mutations are an age-independent thrombotic risk factor in polycythemia vera patients: an observational study. (PubMed, Thromb Haemost)

Our results support the use of molecular testing at diagnosis to help predict which PV patients are at higher risk of developing thrombosis.

4 months ago

Observational data • Journal

DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2)

DNMT3A mutation • ASXL1 mutation • TET2 mutation

4ms

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

4 months ago

Trial completion date • 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)

4ms

Predicting cytopenias, progression, and survival in patients with clonal cytopenia of undetermined significance: a prospective cohort study. (PubMed, Lancet Haematol)

Mutation analysis is advised in patients who have undergone bone marrow examination and have an otherwise-unexplained cytopenia. High-risk genetic mutations and increased numbers of mutations are predictive of both survival and progression within 5 years of presentation, warranting clinical surveillance and, when necessary, intervention.

4 months ago

Journal

TP53 (Tumor protein P53) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • DDX41 (DEAD-Box Helicase 41)

TP53 mutation • DNMT3A mutation • ASXL1 mutation • SRSF2 mutation

4ms

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

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

4 months ago

Journal

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

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

4ms

Cancer predisposition signaling in Beckwith-Wiedemann Syndrome drives Wilms tumor development. (PubMed, Br J Cancer)

While WT predisposition in BWS is well-established, as are 11p15 alterations in nonBWS-WT, this study focused on stratifying tumor genomics by 11p15 status. Further investigation of our findings may identify novel therapeutic targets in WT oncogenesis.

4 months ago

Journal

AXL (AXL Receptor Tyrosine Kinase) • ASXL1 (ASXL Transcriptional Regulator 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • BCORL1 (BCL6 Corepressor Like 1)

ASXL1 mutation • CTNNB1 expression

4ms

Reduced duration and dosage of venetoclax is efficient in newly diagnosed patients with acute myeloid leukemia. (PubMed, Hematology)

The combination of Venetoclax (VEN) and Azacitidine (AZA) increases survival outcomes and yields excellent responses in patients with acute myeloid leukemia (AML). Response rates were favorable, with median survival in agreement with the findings of earlier reports, offering valuable insights for optimizing VEN-based regimens. In summary, the VEN combination regimen is effective for the treatment of newly diagnosed AML patients in the real world despite VEN dose reductions .

4 months ago

Journal

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • ASXL1 (ASXL Transcriptional Regulator 1)

NPM1 mutation • ASXL1 mutation

Venclexta (venetoclax) • azacitidine

4ms

Mutated ASXL1 upregulates mTOR expression in renal cell carcinoma with fibromyomatous stroma. (PubMed, Virchows Arch)

The tumor cells were positive for mTOR expression. This case may indicate that altered mTOR expression, but not limited to mutated TSC/mTOR gene, that participates in the pathogenesis of RCC FMS.

4 months ago

Journal • Stroma

mTOR (Mechanistic target of rapamycin kinase) • ASXL1 (ASXL Transcriptional Regulator 1)

ASXL1 mutation • MTOR mutation

5ms

Effect of clonal hematopoiesis in remission on hematopoiesis recovery in patients with NPM1 mutated acute myeloid leukemia after chemotherapy (PubMed, Zhonghua Xue Ye Xue Za Zhi)

Forty-one patients were induced with intensity chemotherapy ("7 + 3"), whereas 45 patients were treated with low-dose cytarabine-based induction chemotherapy...Furthermore, univariate analysis indicated that age, induced chemotherapy program, and CH in remission were risk factors for platelet recovery, whereas multivariate analysis indicated that induced chemotherapy program and CH in remission were independent risk factors for platelet recovery (HR=0.454, P=0.001 and HR=0.520, P=0.027, respectively) . CH in remission delays the hematopoietic recovery of patients with NPM1(mut) AML after chemotherapy.

5 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2)

IDH2 mutation • NPM1 mutation • DNMT3A mutation • ASXL1 mutation • TET2 mutation

cytarabine