Comparative analysis of the average binding free energies of these predicted potent compounds with known SOS1 small molecule inhibitors revealed that the identified compounds display similar or even superior predicted binding affinities compared to the known inhibitors. These findings offer valuable insights into the potential of these compounds as candidates for further development as effective anti-cancer agents.

9 days ago

Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation

SH2B3 alterations in a novel genetic condition, juvenile myelomonocytic leukemia, and myeloproliferative neoplasia. (PubMed, Haematologica)

Not available.

9 days ago

Journal

SH2B3 (SH2B Adaptor Protein 3)

SH2B3 alteration

14d

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 | Not yet recruiting --> Recruiting

14 days ago

Enrollment open

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation • CBL mutation • Chr t(9;11)

30d

03-OHD-104: Phase 1 Study of Shattuck Labs (SL)-172154 in Subjects With MDS or AML (clinicaltrials.gov)

P1, N=160, Recruiting, Shattuck Labs, Inc. | N=107 --> 160 | Trial completion date: Oct 2024 --> Dec 2025 | Trial primary completion date: Feb 2024 --> Apr 2025

30 days ago

Enrollment change • Trial completion date • Trial primary completion date • Combination therapy

TP53 (Tumor protein P53)

TP53 mutation

Venclexta (venetoclax) • azacitidine • SL-172154

HA-1 T TCR T Cell Immunotherapy for the Treatment of Patients With Relapsed or Refractory Acute Leukemia After Donor Stem Cell Transplant (clinicaltrials.gov)

P1, N=24, Suspended, Fred Hutchinson Cancer Center | Trial completion date: Jul 2025 --> Jul 2028 | Trial primary completion date: Oct 2024 --> Oct 2027

1 month ago

Trial completion date • Trial primary completion date

HLA-A (Major Histocompatibility Complex, Class I, A) • CD4 (CD4 Molecule)

HLA-A*02:01

fludarabine IV

Long-term remission of infantile Takayasu arteritis associated with germline CBL syndrome after allogeneic hematopoietic stem cell transplantation: A case report and literature review. (PubMed, Transpl Immunol)

The pathogenesis of vasculitis in CBL syndrome appears to involve dysregulated T cell function and possibly increased angiogenesis. This case advances the understanding of vascular involvement in CBL syndrome and of the genetic, immune, and vascular interplay in TA, offering insights for treating CBL syndrome and broader TA.

1 month ago

Clinical • Observational data • Retrospective data • Review • Journal

CBL (Cbl proto-oncogene)

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

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

US Study of ECT-001-CB in Pediatric and Young Adult Patients With High-Risk Myeloid Malignancies (clinicaltrials.gov)

P1/2, N=12, Recruiting, ExCellThera inc. | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2023 --> Jun 2026

2 months ago

Trial completion date • Trial primary completion date

HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • CD34 (CD34 molecule)

cyclophosphamide • clofarabine • fludarabine IV • thiotepa • busulfan • ECT-001-CB

2ms

CD45RA Depleted Peripheral Stem Cell Addback for Viral or Fungal Infections Post TCRαβ/CD19 Depleted HSCT (clinicaltrials.gov)

P=N/A, N=50, Recruiting, Children's Hospital of Philadelphia | N=30 --> 50 | Trial completion date: Jan 2024 --> Jan 2026 | Trial primary completion date: Jan 2024 --> Feb 2025

2 months ago

Enrollment change • Trial completion date • Trial primary completion date

cyclophosphamide

3ms

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, Not yet recruiting, Children's Oncology Group

3 months ago

New P1 trial

cytarabine • methotrexate • leucovorin calcium • fludarabine IV • Starasid (cytarabine ocfosfate) • imetelstat (GRN163L)

3ms

A Phase 1 Trial of CIML NK Cell Infusion for Myeloid Disease Relapse After Hematopoietic Cell Transplantation (clinicaltrials.gov)

P1, N=50, Enrolling by invitation, Dana-Farber Cancer Institute | Active, not recruiting --> Enrolling by invitation

3 months ago

Enrollment open

IL2 (Interleukin 2)

cyclophosphamide • fludarabine IV • CIML NK

3ms

HAP2HCT: TCRαβ-depleted Progenitor Cell Graft With Additional Memory T-cell DLI, Plus Selected Use of Blinatumomab, in Naive T-cell Depleted Haploidentical Donor Hematopoietc Cell Transplantation for Hematologic Malignancies (clinicaltrials.gov)

P2, N=140, Active, not recruiting, St. Jude Children's Research Hospital | Recruiting --> Active, not recruiting

3 months ago

Enrollment closed

FLT3 (Fms-related tyrosine kinase 3) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • WT1 (WT1 Transcription Factor) • CREBBP (CREB binding protein) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • HOXA9 (Homeobox A9) • NUP214 (Nucleoporin 214) • CBFA2T3 (CBFA2/RUNX1 Partner Transcriptional Co-Repressor 3) • GLIS2 (GLIS Family Zinc Finger 2) • KAT6A (Lysine Acetyltransferase 6A) • KDM5A (Lysine Demethylase 5A) • DEK (DEK Proto-Oncogene) • AFDN (Afadin, Adherens Junction Formation Factor) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor)

FLT3-ITD mutation • WT1 mutation • MLL fusion • NUP98-NSD1 fusion

cyclophosphamide • Blincyto (blinatumomab) • melphalan • fludarabine IV • thiotepa • Neupogen (filgrastim)

3ms

LIMBER: Safety and Tolerability Study of INCB057643 in Participants With Myelofibrosis and Other Advanced Myeloid Neoplasms (clinicaltrials.gov)

P1, N=216, Recruiting, Incyte Corporation | N=138 --> 216

3 months ago

Enrollment change • Metastases

Jakafi (ruxolitinib) • INCB57643

4ms

Risk-adapted Donor Lymphocyte Infusion After Allo-HSCT in Children With Hematologic Malignancy (clinicaltrials.gov)

P1/2, N=50, Active, not recruiting, St. Petersburg State Pavlov Medical University | Recruiting --> Active, not recruiting | Trial completion date: Apr 2023 --> Apr 2024

4 months ago

Enrollment closed • Trial completion date

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2)

TP53 mutation • MLL rearrangement

4ms

A Phase II Pediatric Study of a Graft-VS.-Host Disease (GVHD) Prophylaxis Regimen With no Calcineurin Inhibitors After Day +60 Post First Allogeneic Hematopoietic Cell Transplant for Hematological Malignancies (clinicaltrials.gov)

P2, N=32, Recruiting, St. Jude Children's Research Hospital

4 months ago

Trial completion date • Trial primary completion date

Jakafi (ruxolitinib) • cyclophosphamide • fludarabine IV • mesna • thiotepa • busulfan • cyclosporine

4ms

03-OHD-104: Phase 1 Study of Shattuck Labs (SL)-172154 in Subjects With MDS or AML (clinicaltrials.gov)

P1, N=107, Recruiting, Shattuck Labs, Inc.

4 months ago

Trial completion date • Trial primary completion date • Combination therapy

TP53 (Tumor protein P53)

TP53 mutation

Venclexta (venetoclax) • azacitidine • SL-172154

4ms

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

P2, N=20, Not yet recruiting, University of Florida

4 months ago

Trial completion date • Trial initiation date • Trial primary completion date

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation • CBL mutation • Chr t(9;11)

4ms

LNK/SH2B3 as a novel driver in juvenile myelomonocytic leukemia. (PubMed, Haematologica)

Lastly, we describe two patients with JMML and SH2B3 mutations who were treated with the JAK1/2 inhibitor ruxolitinib. This report expands the spectrum of initiating mutations in JMML and raises the possibility of targeting the JAK/STAT pathway in patients with SH2B3 mutations.

4 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SH2B3 (SH2B Adaptor Protein 3)

KRAS mutation • NF1 mutation • CBL mutation

Jakafi (ruxolitinib)

4ms

Noonan Syndrome-related Myeloproliferative Disorder Occurring in the Neonatal Period: Case Report and Literature Review. (PubMed, J Pediatr Hematol Oncol)

Eight other cases of NS/MPD with neonatal onset are also summarized. The initial presentation varied, and the prognosis was considered poor compared with previous reports of NS/MPD.

4 months ago

Review • Journal

PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)

PTPN11 mutation

4ms

SOSBiomarker: Sinusoidal Obstruction Syndrome for Stem Cell Transplant Patients Biomarker Study (clinicaltrials.gov)

P=N/A, N=80, Completed, Indiana University | Active, not recruiting --> Completed

4 months ago

Trial completion

4ms

APAL2020SC: The Pediatric Acute Leukemia (PedAL) Screening Trial - A Study to Test Bone Marrow and Blood in Children With Leukemia That Has Come Back After Treatment or Is Difficult to Treat - A Leukemia & Lymphoma Society and Children's Oncology Group Study (clinicaltrials.gov)

P1/2, N=960, Recruiting, LLS PedAL Initiative, LLC | Phase classification: P2 --> P1/2

4 months ago

Phase classification

KMT2A (Lysine Methyltransferase 2A)

5ms

Too many white cells-TAM, JMML, or something else? (PubMed, Hematology Am Soc Hematol Educ Program)

Early recognition of these and other myeloproliferative disorders is important and requires a clinician to be aware of these diagnoses and have a clear understanding of their presentations. This paper discusses the presentation and evaluation of leukocytosis when myeloproliferative disorders are part of the differential and reviews different concepts regarding treatment strategies.

5 months ago

Journal

GATA1 (GATA Binding Protein 1)

5ms

A Comprehensive Genomic Proﬁling of Myeloid Malignancies Demonstrates Mutational Spectrum of DNA Variants Including FLT3-ITDs, and Gene Fusions (ASH 2023)

"Not for use in diagnostic procedures. )"

5 months ago

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR1 (Fibroblast growth factor receptor 1) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 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) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • BCOR (BCL6 Corepressor) • PML (Promyelocytic Leukemia) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • CALR (Calreticulin) • KAT6A (Lysine Acetyltransferase 6A) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • ANKRD26 (Ankyrin Repeat Domain Containing 26)

FLT3-ITD mutation • TET2 mutation • FGFR1 fusion

Oncomine Myeloid Assay GX • Oncomine Myeloid Research Assay

5ms

Detection of KMT2A Partial Tandem Duplications ( KMT2A-PTDs) in Healthy Donors Using Next Generation Sequencing (ASH 2023)

"Not for use in diagnostic procedures. )"

5 months ago

Clinical

KMT2A (Lysine Methyltransferase 2A)

KMT2A-PTD • MLL fusion • MLL-PTD

Oncomine Myeloid Assay GX

5ms

Analysis of Methylation Level and Clinical Characteristics of Juvenile Myelomonocytic Leukemia (ASH 2023)

high risk factors such as age at first diagnosis, PTPN11 mutation and compound mutation are significantly correlated with methylation in patients.

5 months ago

Clinical

KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)

KRAS mutation • NRAS mutation • NF1 mutation • ALK fusion • ALK mutation • PTPN11 mutation • CBL mutation

5ms

Severe RAS-Associated Lymphoproliferative Disease Case with Increasing αβ Double-Negative T Cells with Atypical Features. (PubMed, J Clin Immunol)

The present case is complicated with SLE, suggesting the involvement of Th17-like αβDNTs in the disease pathogenesis. Examining the characteristics of αβDNTs in RALD, JMML, and ALPS may reveal the pathologies in these cases.

5 months ago

Journal • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CD8 (cluster of differentiation 8) • CCR4 (C-C Motif Chemokine Receptor 4) • IL17A (Interleukin 17A) • CCR6 (C-C Motif Chemokine Receptor 6)

5ms

Phase 1 Study of Shattuck Labs (SL)-172154 in Subjects With MDS or AML (clinicaltrials.gov)

P1, N=107, Recruiting, Shattuck Labs, Inc. | Phase classification: P1a/1b --> P1

5 months ago

Phase classification • Combination therapy

TP53 (Tumor protein P53)

TP53 mutation

Venclexta (venetoclax) • azacitidine • SL-172154

5ms

Germline bi-allelic SH2B3/LNK alteration predisposes to a neonatal juvenile myelomonocytic leukemia-like disorder. (PubMed, Haematologica)

However, progression to thrombocythemia and immunity-related pathologies may be of concern later in life. Bi-allelic SH2B3 germline mutations thus define a new condition predisposing to a JMML-like disorder, suggesting that the JAK pathway deregulation is capable of initiating JMML, and opening new therapeutic options.

5 months ago

Journal

SH2B3 (SH2B Adaptor Protein 3)

SH2B3 alteration

5ms

Epigenetic Profiling of PTPN11 Mutant JMML Hematopoietic Stem and Progenitor Cells Reveals an Aberrant Histone Landscape. (PubMed, Cancers (Basel))

Consistent with these data, assay for transposase-accessible chromatin with sequencing (ATAC-seq) analysis revealed significant alterations in chromatin profiles at loci encoding post-translational modification enzymes, strongly suggesting their mis-regulated expression. Collectively, this study reveals histone modification pathways as an additional epigenetic abnormality in JMML patient HSPCs, thereby uncovering a new family of potential druggable targets for the treatment of JMML.

5 months ago

Journal

PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)

RAS mutation • PTPN11 mutation

5ms

The Pediatric Acute Leukemia (PedAL) Screening Trial - A Study to Test Bone Marrow and Blood in Children With Leukemia That Has Come Back After Treatment or Is Difficult to Treat - A Leukemia & Lymphoma Society and Children's Oncology Group Study (clinicaltrials.gov)

P2, N=960, Recruiting, LLS PedAL Initiative, LLC | Phase classification: P=N/A --> P2

5 months ago

Phase classification

KMT2A (Lysine Methyltransferase 2A)

6ms

BH3 mimetics and azacitidine show synergistic effects on juvenile myelomonocytic leukemia. (PubMed, Leukemia)

The combination of azacitidine with BCL-X inhibition was superior to BCL-2 inhibition in eliminating JMML cells. Our findings emphasize the need to develop clinically applicable MCL-1 or BCL-X inhibitors in order to enable novel combination therapies in JMML refractory to standard therapy.

6 months ago

Journal

BCL2L1 (BCL2-like 1)

azacitidine

6ms

Biallelic inactivation of the NF1 tumour suppressor gene in juvenile myelomonocytic leukaemia: Genetic evidence of driver function and implications for diagnostic workup. (PubMed, Br J Haematol)

In addition, we found a high incidence of secondary ASXL1 and/or SETBP1 variants in both groups. We conclude that the clinical diagnosis of JMML/NF-1 reliably indicates a NF1-driven JMML subtype, and that careful NF1 analysis should be included in the genetic workup of JMML even in the absence of clinical evidence of NF-1.

6 months ago

Journal

6ms

Stem Cell Transplant for Juvenile Myelomonocytic Leukemia (JMML) (clinicaltrials.gov)

P1/2, N=15, Completed, Masonic Cancer Center, University of Minnesota | Active, not recruiting --> Completed | Trial completion date: Jul 2024 --> Aug 2023

6 months ago

Trial completion • Trial completion date

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

cyclophosphamide • melphalan

6ms

Signaling Pathway Mutations Cooperate with the PICALM/MLLT10 Fusion in a Knock-in AML Mouse Model (ASH 2023)

We aim to functionally validate these findings by establishing mouse models that harbor the C/A fusion as well as mutations in Ptpn11 and other signal transduction genes. These murine models will be immensely valuable for gaining a deeper insight into PICALM/MLLT10-mediated leukemogenesis, studying cooperating mutations and for testing new targeted therapies.

6 months ago

Preclinical

KRAS (KRAS proto-oncogene GTPase) • FLT3 (Fms-related tyrosine kinase 3) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • PAX5 (Paired Box 5) • IKZF3 (IKAROS Family Zinc Finger 3) • HOXA9 (Homeobox A9) • MEIS1 (Meis Homeobox 1) • SOX9 (SRY-Box Transcription Factor 9) • SPI1 (Spi-1 Proto-Oncogene) • GATA1 (GATA Binding Protein 1) • AFF2 (AF4/FMR2 family member 2) • ZEB1 (Zinc Finger E-box Binding Homeobox 1) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor)

KRAS mutation • PTPN11 mutation • CBL mutation • CD19 expression

6ms

Efficacy of Demethylated Drug Combine with Low Dose Chemotherapy in Juvenile Myelomonocytic Leukemia (ASH 2023)

All patients were given Demethylated drug in combination with low-dose chemotherapy, 10 patients decitabine at a dose of 20 mg/m2 for 5 days, supplemented with cytarabine (50-100 mg/m2×3~5 days), and /or etoposide (50 mg/m2×3~5 days), 6 patients Azacytidine at a dose of 75mg/m2 for 7 days combined with homoharringtonine 2mg/m2 for 5-7 days. Demethylated drug in combination with low-dose chemotherapy could reduce JMML patients' tumor burden, improve the general condition, and obtain a clinical response rate of 81.8% after 3 cycles therapy. Therefore, such a combination regimen could be used as a therapeutic option for JMML before HSCT.

6 months ago

Clinical

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • ASXL1 (ASXL Transcriptional Regulator 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • JAK3 (Janus Kinase 3) • SETBP1 (SET Binding Protein 1) • SH2B3 (SH2B Adaptor Protein 3)

KRAS mutation • NRAS mutation • ARID1A mutation • NF1 mutation • ASXL1 mutation • PTPN11 mutation • SRSF2 mutation • SETBP1 mutation • JAK3 mutation

cytarabine • azacitidine • etoposide IV • decitabine • Synribo (omacetaxine mepesuccinate)

6ms

Risk Stratified Treatment for Patients with Newly Diagnosed Juvenile Myelomonocytic Leukemia: A Phase 1/2 Non-Randomized Study of Trametinib and Azacitidine with or without Chemotherapy (ASH 2023)

Trametinib is FDA-approved for the treatment of adults with advanced melanoma with BRAF V600E or V600K mutations and in children with Ras-mutant solid tumors in combination with dabrafenib...High-risk patients will receive trametinib administered once-daily for 28 days in combination with azacitidine, fludarabine, and cytarabine (aza/FLA) administered daily for five days per cycle...The study is open to accrual at all TACL consortium sites. We acknowledge the TACL Consortium's scientific contribution to and participation in this study, including participating member institutions, investigators, research teams, and the TACL Operations Center.

6 months ago

Clinical • P1/2 data • Tumor mutational burden

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SH2B3 (SH2B Adaptor Protein 3)

BRAF V600E • KRAS mutation • NRAS mutation • BRAF V600 • BRAF V600K • NF1 mutation • RAS mutation • CBL mutation

Mekinist (trametinib) • Tafinlar (dabrafenib) • cytarabine • azacitidine • fludarabine IV

6ms

Error-Corrected Next-Generation Sequencing Provides a Comprehensive Overview of the Subclonal Mutation Landscape and Its Prognostic Implications in Juvenile Myelomonocytic Leukemia (ASH 2023)

We successfully performed error-corrected NGS to assess comprehensive subclonal secondary mutational profiles, including very low VAF variants. The presence of subclonal mutations, particularly in RAS pathway genes, was associated with poor OS. These findings provide important information for appropriate risk stratification, which will contribute to the implementation of precision medicine for patients with JMML.

6 months ago

Next-generation sequencing

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • ASXL1 (ASXL Transcriptional Regulator 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • JAK3 (Janus Kinase 3) • SETBP1 (SET Binding Protein 1) • SH2B3 (SH2B Adaptor Protein 3) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

KRAS mutation • RAS mutation • CBL mutation • JAK3 mutation • ZRSR2 mutation

6ms

Efficacy of the Allosteric MEK Inhibitor Trametinib in Relapsed and Refractory Juvenile Myelomonocytic Leukemia: A Report from the Children's Oncology Group (ASH 2023)

Upfront therapies typically include high-dose cytarabine or azacitidine, but the only definitive treatment is hematopoietic stem cell transplantation (HSCT). We conducted an open label, phase 2 trial of trametinib in children with relapsed or refractory JMML. This is the first completed study of a MEK inhibitor in any hematologic malignancy in children. The trial met its primary objective and demonstrated a 50% objective response rate with 70% of patients bridging to a successful HSCT or completing the maximum 12 cycles permitted on study.

6 months ago

Clinical

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)

KRAS mutation • NRAS mutation • NF1 mutation • RAS mutation • CBL mutation • MAP2K1 expression

Mekinist (trametinib) • cytarabine • azacitidine

6ms

Our experience with new integrated Genexus sequencer for simultaneous , detection of Somatic DNA and RNA Aberrations for myeloid neoplasms (AMP 2023)

The Genexus System offers an automated nucleic acid-to-report workflow in 30 hours, allowing an easy-to-use solution with faster turnaround time. When used with the Oncomine Myeloid GX v2 Assay, it provides accurate and comprehensive information on diverse mutations including fusions that are relevant to the study of myeloid cancers.

6 months ago

FLT3 (Fms-related tyrosine kinase 3) • CEBPA (CCAAT Enhancer Binding Protein Alpha)

Oncomine Myeloid Assay GX