News - ASXL1 mutation

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

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

4 days ago

Journal • Metabolomic study

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

TP53 mutation • RUNX1 mutation • ASXL1 mutation

Clonal hematopoiesis of indeterminate potential is a risk factor of gastric cancer: A Prospective Cohort in UK Biobank study. (PubMed, Transl Oncol)

CHIP is associated with gastric cancer in the elderly and contributes to the positive association between DNM3A and ASXL1 mutations and risk of gastric cancer.

7 days ago

Journal

DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1)

ASXL1 mutation

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

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

9 days ago

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

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

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

cyclophosphamide • fludarabine IV

17d

Clonal hematopoiesis of indeterminate potential (CHIP) and its association with treatment outcomes and adverse events in patients with solid tumours. (PubMed, Cancer Res Commun)

We reviewed cfDNA results from a local prospective solid tumour cohort (PREDiCT-l) and two randomized trials: CCTG CO.26 (durvalumab + tremelimumab [D+T] or best supportive care in metastatic colorectal cancer) and CCTG PA.7 (gemcitabine and nab-paclitaxel +/- D+T in metastatic pancreatic adenocarcinoma). CHIP is common in patients with solid tumours. Although not appearing to impact rates of adverse events, CHIP may impact outcomes from immunotherapy or chemotherapy.

17 days ago

Journal • Adverse events • PD(L)-1 Biomarker • IO biomarker

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

ASXL1 mutation • TET2 mutation

Imfinzi (durvalumab) • gemcitabine • albumin-bound paclitaxel • Imjudo (tremelimumab-actl)

23d

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

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

23 days ago

Clinical data • Journal

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

ASXL1 mutation • TET2 mutation • SRSF2 mutation

25d

Prognostic Significance and Treatment Response Associations of Genetic Mutations in Chronic Myelomonocytic Leukemia: A Retrospective Cohort Study. (PubMed, Biomedicines)

This research underscores the pivotal role of targeted genetic profiling in deciphering the progression of CMML and refining therapeutic strategies. The findings emphasize the necessity for advanced genetic screening in managing CMML to better understand individual prognoses and optimize treatment efficacy, thereby offering insights that could lead to personalized treatment approaches.

25 days ago

Retrospective data • Journal

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

ASXL1 mutation • TET2 mutation • SRSF2 mutation

26d

Stayin' Alive: Targeting chromatin regulators of clonal hematopoiesis promotes CD8 T cell stemness. (PubMed, Cancer Res)

By leveraging the finding that patients with enhanced survival in myelodysplastic syndrome (MDS) had T cell mutations in the ASXL1 gene, this study demonstrates that loss of ASXL1 in T cells preserves their stem-cell like properties of self-renewal and survival leading to increased anti-tumor responses when combined with immunotherapy in both mouse models and human cancers. These findings have significant implications for new therapeutic options that target epigenetic modifiers promoting exhaustion together with immune checkpoint blockade to improve response rates in patients.

26 days ago

Journal • IO biomarker

ASXL1 (ASXL Transcriptional Regulator 1)

ASXL1 mutation

Genetic and immunologic features associated with thrombocytopenia progression and poor prognosis in patients with myelofibrosis. (PubMed, Front Med (Lausanne))

ASXL1 mutation and low CD45RA+CD4+ T-cell counts correlated with progression to thrombocytopenia. Our findings underscore the clinical significance of thrombocytopenia dynamics in MF progression and prognosis, with implications for patient management and therapeutic interventions.

1 month ago

Journal

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ASXL1 (ASXL Transcriptional Regulator 1)

IDH1 mutation • ASXL1 mutation

Elevated serum direct bilirubin is predictive of a poor prognosis for primary myelodysplastic syndrome. (PubMed, BMC Cancer)

An elevated DBIL level was identified as an independent adverse prognostic factor for MDS patients. An individualized prediction model was established and validated to improve prediction of OS and LFS.

1 month ago

Retrospective data • Journal

KRAS (KRAS proto-oncogene GTPase) • ASXL1 (ASXL Transcriptional Regulator 1) • B2M (Beta-2-microglobulin)

KRAS mutation • ASXL1 mutation

2ms

Clinical outcomes of patients diagnosed with SETBP1 mutated myeloid neoplasms. (PubMed, Leuk Lymphoma)

On multivariate analysis, age ≥ 70 years (p = 0.004) and higher peripheral blood blasts (p = 0.02) had worse OS. Patients with Ile871m had lower OS when compared with Asp868m and Gly870m (5.5 months vs. 17.4 and 17 months, respectively, p = 0.1).

2 months ago

Clinical data • Journal

ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • SETBP1 (SET Binding Protein 1)

ASXL1 mutation • SRSF2 mutation • SETBP1 mutation

2ms

DNMT3A, TET2, and ASXL1 (DTA) Mutations Are Associated with Thrombosis and Bleeding in Patients with Myeloproliferative Neoplasms (ASH 2024)

Conclusions : DTA mutations detected with a clinically used NGS panel in patients with MPN are associated with increased risk of bleeding complications, as well as increased thrombotic risk in a subgroup of patients. These findings support the incorporation of molecular panel analyses in thrombosis and bleeding risk assessment in MPN, and merit further investigation.

2 months ago

Clinical

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

ASXL1 mutation • TET2 mutation • JAK2 V617F • JAK2 mutation

Archer® VariantPlex® Myeloid panel

2ms

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

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

2 months ago

Clinical • Biopsy

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • SETBP1 (SET Binding Protein 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

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

Oncomine Myeloid Research Assay

2ms

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

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

2 months ago

Clinical • Next-generation sequencing

FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2)

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

TruSight Myeloid Sequencing Panel

Rydapt (midostaurin)

2ms

Clonal Evolution of TP53 Configurations with Treatment Predict Prognosis in Myeloid Neoplasms (ASH 2024)

Such information will be invaluable for making treatment decisions in this grave prognostic disease otherwise. Ongoing work will dissect the exact treatment modalities and their influence on the TP53MT configurational switch.

2 months ago

TP53 (Tumor protein P53) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2)

TP53 mutation • ASXL1 mutation • TET2 mutation • SF3B1 mutation

TruSight Myeloid Sequencing Panel

2ms

Diagnosis and Risk Stratification of Acute Myeloid Leukemia, Myelodysplasia -Related (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)

Molecular genetic information plays a crucial role in diagnosing AML-MR, highlighting the importance of genetics in diagnosis and prognosis. Most AML-MR patients fall into poor prognosis categories, necessitating early intensive and targeted therapy for better survival outcomes.

2 months ago

Journal

ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor)

ASXL1 mutation • SRSF2 mutation • BCOR mutation

2ms

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.

2 months 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

2ms

Cohesin RAD21 Gene Promoter Methylation in Patients with Acute Myeloid Leukemia. (PubMed, Life (Basel))

This is the first study which provides evidence for a possible pathogenetic role of RAD21 promoter methylation in AML development and especially in AML with trisomy 8. Further studies of RAD21 promoter methylation in large series of different AML genetic subgroups may contribute to the elucidation of AML pathogenesis and to the identification of new epigenetic biomarkers with diagnostic and prognostic value.

2 months ago

Journal

ASXL1 (ASXL Transcriptional Regulator 1) • RAD21 (RAD21 Cohesin Complex Component)

ASXL1 mutation

2ms

Inflammation in myelodysplastic syndrome pathogenesis. (PubMed, Semin Hematol)

Chronic inflammation also drives metabolic reprogramming and immune system deregulation, further promoting the expansion of malignant clones. This review underscores the urgent need to fully elucidate the role of inflammation in MDS initiation and highlights the potential of the therapeutical targeting of inflammatory pathways as an early intervention in MDS.

2 months ago

Journal

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

DNMT3A mutation • ASXL1 mutation • TET2 mutation

2ms

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

2 months 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)

3ms

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.

3 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

3ms

Distinct mutation features and its clinical significance in myelodysplastic syndromes with normal karyotype. (PubMed, Ann Hematol)

In summary, MDS with NK showed distinct mutation features from those with AK. High-frequency gene mutations together with the mutational evolution suggested the diagnostic and monitoring significance of next generation sequencing for NK-MDS.

3 months ago

Journal

TP53 (Tumor protein P53) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)

TP53 mutation • DNMT3A mutation • ASXL1 mutation • TET2 mutation • U2AF1 mutation

3ms

Genetic Response of Chronic Neutrophilic Leukemia With CSF3R T618I, SETBP1, and ASXL1 Mutations After Decitabine Therapy. (PubMed, Am J Ther)

No abstract available

3 months ago

Journal

ASXL1 (ASXL Transcriptional Regulator 1) • CSF3R (Colony Stimulating Factor 3 Receptor) • SETBP1 (SET Binding Protein 1)

ASXL1 mutation • CSF3R T618I

decitabine

3ms

Prognostic impact of DTA mutation and co-occurring mutations in patients with myelodysplastic syndrome. (PubMed, Mol Biol Rep)

DTA mutations are frequently observed in patients with MDS, often accompanied by genes involved in RNA splicing and transcription factors like SF3B1 and RUNX1. DTA and concomitant mutations affect prognosis in MDS patients and RUNX1 was identified as an independent poor prognostic factor in patients with DTA mutations.

3 months ago

Retrospective data • Journal

TP53 (Tumor protein P53) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • 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) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • SETBP1 (SET Binding Protein 1)

TP53 mutation • DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • TET2 mutation • SF3B1 mutation • U2AF1 mutation

3ms

This study reveals how age-associated somatic mutations in the microenvironment may be driving DCC reactivation and relapse. These findings may provide a new genetic biomarker of relapse and inform CH-targeted trials to improve breast cancer patient outcomes.

3 months ago

Metastases

HER-2 (Human epidermal growth factor receptor 2) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • IL1B (Interleukin 1, beta)

DNMT3A mutation • ASXL1 mutation • TET2 mutation

MSK-IMPACT

3ms

Presence of triple positive driver mutations in JAK2, CALR and MPL in primary myelofibrosis: a case report and literature review. (PubMed, Hematology)

The patient was diagnosed with PMF and treated with ruxolitinib and COPD therapy...The rare coexistence of JAK2, CALR, and MPL mutations challenges the assumption of their mutual exclusivity. Further study of these mutations is essential for developing better treatment strategies.

3 months ago

Review • Journal

JAK2 (Janus kinase 2) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • STAG2 (Stromal Antigen 2) • CALR (Calreticulin)

ASXL1 mutation • SF3B1 mutation • SRSF2 mutation • STAG2 mutation • JAK2 mutation

Jakafi (ruxolitinib)

3ms

Early drivers of clonal hematopoiesis shape the evolutionary trajectories of de novo acute myeloid leukemia. (PubMed, medRxiv)

Thus, early CH-associated mutations that precede malignant transformation subsequently shape the evolutionary trajectories of AML through diagnosis, therapy, and relapse. DNMT3A , TET2 and ASXL1 mutations persist through AML-directed therapy Distinct CH-related mutations shape the evolutionary trajectories of AML from diagnosis through relapse.

3 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2)

FLT3 mutation • NPM1 mutation • DNMT3A mutation • ASXL1 mutation • TET2 mutation • CBL mutation • SRSF2 mutation • FLT3 mutation + NPM1 mutation

7ms

Integrated Clinical Genotype-phenotype Characteristics of STAT3-mutated Myeloid Neoplasms. (PubMed, Clin Cancer Res)

STAT3 mutation is present in various MNs, but not in MPN. It is often an early event or occurs upon leukemic transformation, suggesting an important role in the pathogenesis and progression of MNs by activating JAK-STAT pathway. It may help identify a subset of patients with MNs who may benefit from targeted therapy.

7 months ago

Journal

ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • STAT3 (Signal Transducer And Activator Of Transcription 3) • SETBP1 (SET Binding Protein 1)

ASXL1 mutation • TET2 mutation • SRSF2 mutation • STAT3 mutation • STAT3 Y640F

7ms

STUDY OF THE MOLECULAR GENETIC PROFILE OF HIGH-RISK AML PATIENTS USING NEXT GENERATION SEQUENCING (EHA 2024)

Highly heterogeneous molecular genetic profile is present in patients from adverse risk group. Mutations ingenes that activate intracellular signaling pathways are most common in high-risk AML. The presence of morethan 6 mutations and ASXL1mut+ and SRSF2mut+ status negatively affect the survival of patients.

7 months ago

Clinical • Next-generation sequencing

TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • NF1 (Neurofibromin 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • KMT2C (Lysine Methyltransferase 2C) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • FAT1 (FAT atypical cadherin 1) • CUX1 (cut like homeobox 1)

TP53 mutation • DNMT3A mutation • ASXL1 mutation • PTPN11 mutation • SRSF2 mutation

TruSight Myeloid Sequencing Panel

8ms

Targeting BIRC5 as a Therapeutic Approach to Overcome ASXL1-associated Decitabine Resistance. (PubMed, Cancer Lett)

Furthermore, our experimental evidence demonstrated that the small-molecule inhibitor of BIRC5 (YM-155) synergistically sensitized ASXL1 deficient cells to decitabine treatment. This study sheds light on the molecular mechanisms underlying the ASXL1-associated HMA resistance and proposes a promising therapeutic strategy for improving treatment outcomes in affected individuals.

8 months ago

Journal

ASXL1 (ASXL Transcriptional Regulator 1) • BIRC5 (Baculoviral IAP repeat containing 5)

ASXL1 mutation

decitabine

8ms

Measurable residual disease monitoring by ddPCR in the early posttransplant period complements the traditional MFC method to predict relapse after HSCT in AML/MDS: a multicenter retrospective study. (PubMed, J Transl Med)

ddPCR-MRD is a feasible approach to predict relapse after allo-HSCT in AML/MDS patients with non-DTA genes and is more accurate when combined with MFC.

8 months ago

Retrospective data • Journal • Post-transplantation

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

DNMT3A mutation • ASXL1 mutation • TET2 mutation

8ms

Single-Cell DNA Sequencing Reveals an Evolutionary Pattern of CHIP in Transplant Eligible Multiple Myeloma Patients. (PubMed, Cells)

Moreover, we observed a tendency of CHIP-positive patients to achieve a suboptimal response to therapy compared to those without. A sub-clone dynamic of high-fitness mutations over time was confirmed.

8 months ago

Journal

DNMT3A (DNA methyltransferase 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CD34 (CD34 molecule)

DNMT3A mutation • ASXL1 mutation • TET2 mutation • EZH2 mutation

8ms

A comparative analysis of the clinical and genetic profiles of blast phase BCR::ABL1-negative myeloproliferative neoplasm and acute myeloid leukemia, myelodysplasia-related. (PubMed, Int J Lab Hematol)

MPN-BP and AML-MR harbor similar somatic mutations and clinical outcomes, suggesting a unified clinical disease entity.

8 months ago

Journal

TP53 (Tumor protein P53) • ABL1 (ABL proto-oncogene 1) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • SETBP1 (SET Binding Protein 1) • CALR (Calreticulin)

TP53 mutation • DNMT3A mutation • ASXL1 mutation • TET2 mutation • SRSF2 mutation • U2AF1 mutation

8ms

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.

8 months 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)

8ms

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.

8 months 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

8ms

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.

8 months ago

Journal

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

ASXL1 mutation • JAK2 V617F

8ms

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.

8 months ago

Journal

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

ASXL1 mutation

9ms

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

9 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

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.

9 months 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

9ms

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.

9 months ago

Review • Journal

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

IDH2 mutation • ASXL1 mutation

Venclexta (venetoclax) • decitabine • thalidomide

9ms

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.

9 months 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)

9ms

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.

9 months 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

9ms

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.

9 months 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