News - CSF3R T618I - LARVOL VERI

11ms

Dual ASXL1 and CSF3R mutations drive myeloid biased stem cell expansion and enhance neutrophil differentiation. (PubMed, Blood Adv)

While we see the expected decrease in H2AK119ub in Asxl1-mutant cells, this effect is reversed when CSF3R is also mutated, suggesting a complex interplay between these mutations in regulating chromatin dynamics during hematopoiesis. Our findings highlight context-dependent effects of ASXL1 mutation in myeloid disorders and provide insights into the mechanisms underlying neutrophil differentiation in ASXL1 and CSF3R dual mutant MPN.

11 months ago

Journal

ASXL1 (ASXL Transcriptional Regulator 1) • CSF3R (Colony Stimulating Factor 3 Receptor)

ASXL1 mutation • CSF3R T618I • CSF3R mutation • ASXL1 Y588X

over1year

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.

over 1 year 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)

over1year

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.

over 1 year 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

almost2years

Antineoplastic effects of pharmacological inhibitors of aurora kinases in CSF3R-driven cells. (PubMed, Blood Cells Mol Dis)

In the present study, the cellular and molecular effects of pharmacological inhibitors of aurora kinases, such as aurora A inhibitor I, AZD1152-HQPA, and reversine, were evaluated in Ba/F3 expressing the CSF3R mutation...Reversine more efficiently modulated genes associated with cell cycle and apoptosis compared to other drugs. In summary, our findings shed new insights into the use of AURKB inhibitors in the context of CNL.

almost 2 years ago

Journal • PARP Biomarker

ABL1 (ABL proto-oncogene 1) • CSF3R (Colony Stimulating Factor 3 Receptor) • AURKA (Aurora kinase A) • AURKB (Aurora Kinase B)

CSF3R T618I • CSF3R mutation

barasertib-HQPA (AZD2811)

2years

Chronic neutrophilic leukemia/chronic eosinophilic leukemia (PubMed, Rinsho Ketsueki)

Ruxolitinib, a JAK2 inhibitor, provided a promising therapeutic effect in a phase II study...Anti-CD52 antibody, alemtuzumab, or anti-IL-5 antibody, mepolizumab, are promising drugs to control symptoms that are associated with hypereosinophilic syndrome. Allo-SCT is anticipated as a curative treatment for CEL, but the evidence of Allo-SCT for CEL is still limited. Further study is required to define the treatment strategy.

2 years ago

Clinical Trial,Phase II • Journal

CSF3R (Colony Stimulating Factor 3 Receptor) • IL5 (Interleukin 5)

CSF3R T618I • CSF3R mutation

Jakafi (ruxolitinib) • Campath (alemtuzumab)

2years

CSF3R T618I Collaborates With RUNX1-RUNX1T1 to Expand Hematopoietic Progenitors and Sensitizes to GLI Inhibition. (PubMed, Hemasphere)

Both primary hematopoietic cells and the t(8;21) positive AML cell line SKNO-1 showed increased sensitivity to the GLI inhibitor GANT61 when expressing CSF3R T618I. Our findings suggest that during leukemogenesis, the RUNX1-RUNXT1 fusion and CSF3R mutation act in a synergistic manner to alter hedgehog signaling, which can be exploited therapeutically.

2 years ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • CSF3R (Colony Stimulating Factor 3 Receptor) • CD34 (CD34 molecule) • GLI2 (GLI Family Zinc Finger 2)

RUNX1-RUNX1T1 fusion • CSF3R T618I • CSF3R mutation

2years

Granulocyte-colony stimulating factor-producing multiple myeloma presenting with neutrophilia (PubMed, Rinsho Ketsueki)

The patient was diagnosed using G-CSF-producing myeloma and was treated with daratumumab, lenalidomide, and dexamethasone. However, the clinical characteristics and long-term prognosis of G-CSF-producing myeloma remain unknown. Additional case gathering and investigations are required.

2 years ago

Journal

CSF3R (Colony Stimulating Factor 3 Receptor)

CSF3R T618I • CSF3R mutation

lenalidomide • Darzalex (daratumumab)

over2years

Chronic neutrophilic leukemia preceded by myelodysplastic syndromes. (PubMed, Int J Hematol)

This suggests that CNL was clonally developed from the founding clone of MDS and CSF3R mutation contributes to the development of CNL in the present case. These findings provide insights into the pathology of CNL.

over 2 years ago

Journal

ASXL1 (ASXL Transcriptional Regulator 1) • CSF3R (Colony Stimulating Factor 3 Receptor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • SETBP1 (SET Binding Protein 1)

ASXL1 mutation • U2AF1 mutation • CSF3R T618I • CSF3R mutation