News - CBL mutation - LARVOL VERI

6d

Alpha/Beta T Cell and CD19+ B Cell Depletion in Allogeneic Stem Cell Transplantation in Patients With Malignant Diseases (clinicaltrials.gov)

P2, N=20, Recruiting, University of Florida | Trial completion date: May 2027 --> May 2028 | Trial primary completion date: May 2026 --> May 2027

6 days ago

Trial completion date • Trial primary completion date

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FLT3 (Fms-related tyrosine kinase 3)

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FLT3 mutation • CBL mutation

14d

Molecular Advances in Juvenile Myelomonocytic Leukemia and Associated RASopathy. (PubMed, Cancers (Basel))

Both genotype and DNA methylation subclassification have been integrated into clinical decision-making, incorporating pretransplant azacitidine, watch-and-wait approaches for favorable-risk patients, and emerging targeted therapies including MEK inhibitors. This review synthesizes recent advances in understanding JMML as a bona fide RASopathy; provides a diagnostic algorithm, molecular landscapes, and prognostic models; and highlights opportunities for molecularly targeted therapeutic intervention.

14 days ago

Review • Journal

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KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SH2B3 (SH2B Adaptor Protein 3)

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KRAS mutation • ROS1 fusion • CBL mutation

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azacitidine

21d

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

P1, N=102, Active, not recruiting, Jacqueline Garcia, MD | Trial completion date: Mar 2027 --> Mar 2030

21 days ago

Trial completion date

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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)

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TP53 mutation • KRAS mutation • NRAS mutation • RUNX1 mutation • RAS mutation • ASXL1 mutation • CBL mutation • Chr del(5q)

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

22d

Chronic myelomonocytic leukemia without increased classical monocyte subsets exhibits a distinct genetic profile, including frequent CBL mutations. (PubMed, Am J Clin Pathol)

Chronic myelomonocytic leukemia without increased CM subsets is associated with a distinct genetic profile characterized by enrichment of CBL mutations. Mechanistically, we hypothesize that CBL mutations promote proinflammatory signaling that contributes to normalization of CM partitioning.

22 days ago

Journal

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IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • TET2 (Tet Methylcytosine Dioxygenase 2)

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TET2 mutation • CBL mutation

1m

NCI-2020-05261: Azacitidine and Quizartinib for the Treatment of Myelodysplastic Syndrome or Myelodysplastic/Myeloproliferative Neoplasm With FLT3 or CBL Mutations (clinicaltrials.gov)

P1/2, N=30, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=58 --> 30

1 month ago

Enrollment closed • Enrollment change

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TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ASXL1 (ASXL Transcriptional Regulator 1)

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TP53 mutation • FLT3-ITD mutation • ASXL1 mutation • CBL mutation

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azacitidine • Vanflyta (quizartinib)

2ms

A Study to Find the Highest Dose of Imetelstat in Combination With Fludarabine and Cytarabine for Patients With AML, MDS or JMML That Has Come Back or Does Not Respond to Therapy (clinicaltrials.gov)

P1, N=36, Recruiting, Children's Oncology Group | Trial completion date: Jun 2026 --> Mar 2028 | Trial primary completion date: Jun 2026 --> Mar 2028

2 months ago

Trial completion date • Trial primary completion date

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NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)

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RAS mutation • CBL mutation

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cytarabine • methotrexate • leucovorin calcium • fludarabine IV • Rytelo (imetelstat) • Starasid (cytarabine ocfosfate)

2ms

Genetic landscape of stage II melanoma identifies CBL as a new driver gene and prognostic biomarker. (PubMed, Br J Cancer)

Our findings suggest CBL as a novel driver gene in melanoma, which is mutated in a relevant fraction of patients. Deletions of 11q23.1-3 including CBL were identified as a prognostic marker indicating a higher risk of recurrence and shorter survival. Furthermore, CBL could support patient stratification to identify high-risk patients who may benefit from adjuvant therapies or intensified monitoring strategies.

2 months ago

Journal

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BRAF (B-raf proto-oncogene) • NF1 (Neurofibromin 1)

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BRAF mutation • RAS mutation • CBL mutation

4ms

Prognostic Model Combining Mutational and Cytogenetic Profiles in Acute Myeloid Leukemia Treated with Venetoclax and Hypomethylating Agents. (PubMed, Blood Cancer Discov)

Compared to existing HMA/VEN-specific models, our model demonstrated superior low- vs. intermediate-risk discrimination (31.9-month separation, p=0.002; HR=0.45, p=0.003), with comparable C-index. Our model supports personalized risk stratification for HMA/VEN-treated AML, pending broader validation.

4 months ago

Journal

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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • JAK2 (Janus kinase 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • MECOM (MDS1 And EVI1 Complex Locus)

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TP53 mutation • KRAS mutation • CBL mutation

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Venclexta (venetoclax)

4ms

Mesothelin Expression in Acute Leukemia: Correlations With Immunophenotype, Cytogenetics, and Mutational Status. (PubMed, Appl Immunohistochem Mol Morphol)

In AML, it correlated with CD33 expression and inv(16)/t(16;16). In conclusion, mesothelin is rare in ALL but enriched in specific AML subtypes and not prognostic for survival.

4 months ago

Journal • IO biomarker

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NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • KMT2A (Lysine Methyltransferase 2A) • MSLN (Mesothelin) • CD38 (CD38 Molecule) • KDM6A (Lysine Demethylase 6A) • CD33 (CD33 Molecule) • GATA2 (GATA Binding Protein 2) • PHF6 (PHD Finger Protein 6) • ITGAX (Integrin Subunit Alpha X) • CBLC (Cbl Proto-Oncogene C)

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NPM1 mutation • CBL mutation

5ms

Sustained response to minimal-dose tagraxofusp in a patient with BPDCN and advanced chronic kidney disease. (PubMed, Ann Hematol)

To our knowledge, this is the first reported case demonstrating the use of tagraxofusp in a patient with BPDCN and advanced chronic kidney disease, showing that even a minimum of tolerated treatment dose can induce a sustained response. Despite the risk of adverse events, tagraxofusp should be considered a viable treatment option for elderly patients with poor performance status and significant comorbidities who are ineligible for intensive chemotherapy or stem cell transplantation, as even limited exposure may achieve meaningful clinical responses.

5 months ago

Journal

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KRAS (KRAS proto-oncogene GTPase) • TET2 (Tet Methylcytosine Dioxygenase 2) • CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

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KRAS mutation • TET2 mutation • CBL mutation

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Elzonris (tagraxofusp-erzs)

5ms

CBL-Mutated Juvenile Myelomonocytic Leukaemia With Loss of Heterozygosity on 11q Detected by Microarray: Not Always Such a Favourable Outcome. (PubMed, Int J Lab Hematol)

CN-LOH was confirmed by single nucleotide polymorphism array. This patient presented with an aggressive clinical course and required an allogeneic stem cell transplant.

5 months ago

Journal

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CBL (Cbl proto-oncogene)

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CBL mutation

6ms

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

P1, N=102, Active, not recruiting, Jacqueline Garcia, MD | Trial completion date: Feb 2026 --> Mar 2027 | Trial primary completion date: Dec 2025 --> May 2026

6 months ago

Trial completion date • Trial primary completion date

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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)

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TP53 mutation • KRAS mutation • NRAS mutation • RUNX1 mutation • RAS mutation • ASXL1 mutation • CBL mutation • Chr del(5q)

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