Analysis of AML with t(4; 12)(q12; p13) translocation by WGS and WTS provides detailed information that separates two subsets distinguished by distinct breakpoint cluster regions on 4q12 and PDGFRA gene expression. The clinical impact of increased PDGFRA gene expression on response to TKI and prognosis as well as the presence of additional fusion transcripts has to be evaluated in further studies.

1 year ago

Clinical • Omic analysis

BCR (BCR Activator Of RhoGEF And GTPase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • ASXL1 (ASXL Transcriptional Regulator 1) • ETV6 (ETS Variant Transcription Factor 6) • ADAMTS3 (ADAM Metallopeptidase With Thrombospondin Type 1 Motif 3) • SCFD2 (Sec1 Family Domain Containing 2)

ASXL1 mutation • PDGFRA mutation • PDGFRA overexpression • PDGFRA fusion

1year

NATRON: A Phase III Study to Evaluate the Efficacy and Safety of Benralizumab in Patients With Hypereosinophilic Syndrome (HES) (clinicaltrials.gov)

P3, N=120, Recruiting, AstraZeneca | Trial completion date: Nov 2024 --> Nov 2026 | Trial primary completion date: Nov 2023 --> May 2024

1 year ago

Trial completion date • Trial primary completion date

PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • FIP1L1 (Factor Interacting With PAPOLA And CPSF1)

FIP1L1-PDGFRA fusion • PDGFRA fusion

1year

Integration of genomic sequencing drives therapeutic targeting of PDGFRA in T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma. (PubMed, Clin Cancer Res)

Refractory T-ALL has not been fully characterized. Alterations in PDGFRA or other targetable kinases may inform therapy for patients with refractory T-ALL who otherwise have limited treatment options. Clinical genomic profiling, in real time, is needed for fully informed therapeutic decision making.

1 year ago

Journal

PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • FIP1L1 (Factor Interacting With PAPOLA And CPSF1)

PDGFRA mutation • PDGFRA fusion

Ayvakit (avapritinib)

1year

Gliomas in adolescents and young adults – experience of cases presented at national AYA multi-disciplinary rounds (SNO 2023)

Within national rounds, there was enrichment of pediatric-type tumors and patients with cancer predisposition syndromes. Targeted agents are available for many of these driver mutations with potential improved outcomes; however, access to these agents in AYA may be limited. Clinicians face complex management questions in this population and underscores the need for a multi-disciplinary approach along with clinical trial opportunities for these patients.

1 year ago

Clinical

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • FGFR (Fibroblast Growth Factor Receptor) • NTRK (Neurotrophic receptor tyrosine kinase)

IDH wild-type • NTRK fusion • PDGFRA fusion

1year

Implementing genomic profiling as standard-of-care for glioblastoma patients. (SNO 2023)

Genomic profiling revealed actionable targets and new therapeutic options for glioblastoma pts. A full and updated overview of patient characteristics, actionable targets and survival data will be presented at the meeting.

1 year ago

Clinical

TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • FGFR (Fibroblast Growth Factor Receptor) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • TMB-H • FGFR mutation • FGFR fusion • MET mutation • PDGFRA mutation • NTRK fusion • PDGFRA fusion

1year

Utility of Next-Generation Sequencing in the Detection of RNA Fusion Genes in Myeloid Malignancies in Singapore (ASH 2023)

Conclusion We have demonstrated that NGS has a high sensitivity for identification of RNA fusion genes, is complementary to conventional cytogenetics testing, and has vast clinical impact in terms of diagnosis, prognostication and clinical management. We advocate for the integration of NGS with DNA and RNA sequencing into routine investigation of suspected myeloid malignancies for a more precise and comprehensive diagnostic approach.

1 year ago

Next-generation sequencing

FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • PML (Promyelocytic Leukemia) • FIP1L1 (Factor Interacting With PAPOLA And CPSF1) • NUP214 (Nucleoporin 214) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • DEK (DEK Proto-Oncogene)

FLT3-ITD mutation • BCR-ABL1 fusion • NF1 mutation • ASXL1 mutation • U2AF1 mutation • CBFB-MYH11 fusion • MLL fusion • PDGFRA fusion

Oncomine Myeloid Research Assay

1year

RNA Fusions and Their Association with DNA Alterations in Myeloid Neoplasia Patients Identified By a Single Tube Multimodal Comprehensive Genomic Profiling Test (ASH 2023)

A robust low-noise RNA fusion detection assay coupled us DNA alterations on myeloid disorders in a single assay enables to fully molecularly characterize acute myeloid leukemias and other myeloid disorders. Frequencies of well-known fusions in a small community-based cohort were similar to studies performed in academic settings with subsets of gene alterations being mutually exclusive from fusions. Larger studies are needed to confirm those associations.

1 year ago

Clinical

FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR1 (Fibroblast growth factor receptor 1) • NPM1 (Nucleophosmin 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • IKZF1 (IKAROS Family Zinc Finger 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • BCOR (BCL6 Corepressor) • CSF3R (Colony Stimulating Factor 3 Receptor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • CCND2 (Cyclin D2) • PHF6 (PHD Finger Protein 6) • CALR (Calreticulin) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor) • ZNF384 (Zinc Finger Protein 384)

FGFR1 fusion • ABL1 fusion • PDGFRA fusion

1year

AZURE: Study of Elenestinib (BLU-263) in Advanced Systemic Mastocytosis (AdvSM) and and Other KIT Altered Hematologic Malignancies (clinicaltrials.gov)

P1/2, N=67, Recruiting, Blueprint Medicines Corporation | Initiation date: Apr 2023 --> Sep 2023

1 year ago

Trial initiation date • Combination therapy • Metastases

PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

KIT mutation • PDGFRA D842V • PDGFRA mutation • KIT D816V • KIT exon 17 mutation • PDGFRA fusion

azacitidine • elenestinib (BLU-263)

over1year

FIP1L1::PDGFRA fusion driving three synchronous haematological malignancies. (PubMed, Pathology)

No abstract available

over 1 year ago

Journal

PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • FIP1L1 (Factor Interacting With PAPOLA And CPSF1)

FIP1L1-PDGFRA fusion • PDGFRA fusion

over1year

The landscape of PDGFRA mutation in Chinese patients with glioma (ESMO 2023)

This type of mutation is mostly found in the non-tyrosine kinase domain. Investigating the PDGFRA map and PDGFRA inhibitors has significant exploratory value.

over 1 year ago

Clinical

KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

PDGFRA D842V • PDGFRA mutation • KIT fusion • PDGFRA fusion

over1year

AZURE: Study of Elenestinib (BLU-263) in Advanced Systemic Mastocytosis (AdvSM) and and Other KIT Altered Hematologic Malignancies (clinicaltrials.gov)

P1/2, N=67, Recruiting, Blueprint Medicines Corporation | Not yet recruiting --> Recruiting

over 1 year ago

Enrollment open • Combination therapy • Metastases

PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

KIT mutation • PDGFRA D842V • PDGFRA mutation • KIT D816V • KIT exon 17 mutation • PDGFRA fusion

azacitidine • elenestinib (BLU-263)

over1year

AZURE: Study of Elenestinib (BLU-263) in Advanced Systemic Mastocytosis (AdvSM) and and Other KIT Altered Hematologic Malignancies (clinicaltrials.gov)

P1/2, N=67, Not yet recruiting, Blueprint Medicines Corporation | N=108 --> 67 | Trial completion date: Nov 2027 --> Nov 2029 | Initiation date: Dec 2022 --> Apr 2023 | Trial primary completion date: Nov 2027 --> Nov 2029

over 1 year ago

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

PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

KIT mutation • PDGFRA D842V • PDGFRA mutation • KIT D816V • KIT exon 17 mutation • PDGFRA fusion

azacitidine • elenestinib (BLU-263)

almost2years

Landscape of known and novel myeloid neoplasia fusions identified by a multimodal comprehensive genomic profiling test in 789 patients (AACR 2023)

Frequencies of well-known fusions in real world data obtained by a robust low-noise RNA fusion assay were similar to other studies done in academic setting. Reliable detection of bona-fide RNA fusions with this clinical test is invaluable for patient care and novel fusion identification.

almost 2 years ago

Clinical

ABL1 (ABL proto-oncogene 1) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • CCND2 (Cyclin D2) • MGP (Matrix Gla Protein) • ZNF384 (Zinc Finger Protein 384)

FGFR1 fusion • ABL1 fusion • PDGFRA fusion

almost2years

FIP1L1::PDGFRA-positive chronic eosinophilic leukemia showing slowly progressive cardiac impairment (PubMed, Rinsho Ketsueki)

We initiated imatinib (100 mg/day), and the eosinophilia disappeared in a month...This case is valuable because it shows the long-term course of the disease, with 15 years of laboratory findings until diagnosis. Our findings suggest that in cases of eosinophilia with an abnormal electrocardiogram, contrast-enhanced cardiac magnetic resonance imaging should be considered earlier.

almost 2 years ago

Review • Journal

PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • FIP1L1 (Factor Interacting With PAPOLA And CPSF1)

FIP1L1-PDGFRA fusion • PDGFRA fusion

imatinib

2years

Clinical Characteristics and Stratified Analysis of Ph-like Acute Lymphoblastic Leukemia in Children: A Retrospective Study from China (ASH 2022)

Ph-like ALL is a heterogeneous group of disorders, Overall survival was significantly different between the different genomic groups. Children with abl1 positive or CRLF2 positive had better survival, while those with PDGFRB positive or abl2 positive had a poor outcome.

2 years ago

Retrospective data

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • JAK2 (Janus kinase 2) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CRLF2 (Cytokine Receptor Like Factor 2) • ABL2 (ABL Proto-Oncogene 2, Non-Receptor Tyrosine Kinase) • CSF1R (Colony stimulating factor 1 receptor)

BCR-ABL1 fusion • ABL2 fusion • JAK2 fusion • PDGFRB fusion • PDGFRA fusion

2years

Fusion Gene Detection and Quantification by Asymmetric Capture Sequencing (aCAP-Seq). (PubMed, J Mol Diagn)

Fusion quantification was linear from 50% to 0.1% and breakpoint locations and sequences identified by NGS were concordant with results obtained by Sanger sequencing. Finally, this new sensitive and cost efficient NGS method allowed integrated analysis of resistant chronic myeloid leukemia patients and will thus be of interest to elucidate the mutational landscape and the clonal architecture of myeloid malignancies driven by these fusion genes at diagnosis, relapse, or progression.

2 years ago

Journal

ABL1 (ABL proto-oncogene 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • FIP1L1 (Factor Interacting With PAPOLA And CPSF1)

FIP1L1-PDGFRA fusion • PDGFRA fusion

2years

CML-216 Hypereosinophilia Syndrome With FIP1L1-PDGFRA Transcript Revealed by Cardiac Involvement. (PubMed, Clin Lymphoma Myeloma Leuk)

Chronic eosinophilic leukemia with FIP1L1-PDGFRA can be serious and fatal in the event of diagnostic delay and the nature of the affected organ. Patients with clinical manifestations consistent with HES should be investigated for evidence of clonality of hematopoiesis and a search for a T-lymphocyte population for treatment decisions.

2 years ago

Journal

PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • FIP1L1 (Factor Interacting With PAPOLA And CPSF1)

FIP1L1-PDGFRA fusion • PDGFRA fusion

imatinib

2years

MPN-092 Paraneoplastic Eosinophilia: An Unusual Initial Presentation of Metastatic Pancreatic Adenocarcinoma. (PubMed, Clin Lymphoma Myeloma Leuk)

The patient was on oxygen and was started on dexamethasone for the hypereosinophilia. We initiated first-line chemotherapy for advanced pancreatic adenocarcinoma with gemcitabine and nab-paclitaxel...She received second-line treatment with mFOLFIRINOX for 12 cycles...It is characterized by a more aggressive disease and dismal outcome. Clinicians must be aware of this condition and must exclude all other causes of hypereosinophilia before making this diagnosis.

2 years ago

Journal

PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • FIP1L1 (Factor Interacting With PAPOLA And CPSF1)

PDGFRA fusion

gemcitabine • albumin-bound paclitaxel • irinotecan • dexamethasone

over2years

MUTATIONAL LANDSCAPE AND CLINICAL OUTCOMES OF PATIENTS WITH MYELOID AND LYMPHOID NEOPLASMS WITH EOSINOPHILIA (MLN-EOS) AND ABNORMALITIES OF PDGFRA, PDGFRB, FGFR1, FLT3 AND JAK REARRANGEMENT (EHA 2022)

Targeted TKI therapies in the upfront setting are associated with excellent outcomes in patients with MLN-Eos. The elucidation of potential mechanisms needs further exploration.

over 2 years ago

Clinical data • Clinical

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • TET2 (Tet Methylcytosine Dioxygenase 2) • ETV6 (ETS Variant Transcription Factor 6) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • PCM1 (Pericentriolar Material 1)

TP53 mutation • PTPN11 mutation • PDGFRA mutation • FGFR1 fusion • PDGFRA rearrangement • PDGFRB mutation • PDGFRA fusion

FoundationOne® Heme CDx

almost3years

A Novel USP25::PDGFRA Gene Fusion in a 78 Year Old Patient with a Myeloid Neoplasm. (PubMed, Lab Med)

The overall outcome of these neoplasms is favorable with imatinib therapy. Herein, we describe an adult female patient with a myeloid neoplasm accompanied by eosinophilia and a novel USP25::PDGFRA gene fusion.

almost 3 years ago

Journal

PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

PDGFRA rearrangement • PDGFRA fusion

imatinib

3years

Upfront Targeted Tyrosine Kinase Inhibitor Therapy Improves Outcome in Patients with Myeloid/Lymphoid Neoplasms with Eosinophilia (ASH 2021)

Upfront TKI can potentially suppress, even in some cases eradicate the malignant clone. The study is limited due to small sample size and retrospective nature, and larger study is needed to validate our observation.

3 years ago

Clinical

FLT3 (Fms-related tyrosine kinase 3) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • JAK2 (Janus kinase 2) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • ETV6 (ETS Variant Transcription Factor 6) • PCM1 (Pericentriolar Material 1)

PDGFRA mutation • FGFR1 fusion • FGFR1 rearrangement • PDGFRA rearrangement • PDGFRB mutation • PDGFRA fusion

3years

t(4;12)(q12;p13) ETV6-rearranged AML without eosinophilia does not involve PDGFRA: relevance for imatinib insensitivity. (PubMed, Blood Adv)

Our findings highlight the importance of using a sequencing-based assay to confirm the presence of targetable gene fusions, particularly in genomic regions such as 4q12 with many clinically relevant genes that are too close to resolve by chromosome or FISH analysis. Finally, combining our data and review of the literature, we show that sequence-confirmed ETV6-PDGFRA fusions are typically found in eosinophilic disorders (3 of 3 cases), and patients with t(4;12)(q12;p13) without eosinophilia are found to have other 4q12 partners on sequencing (17 of 17 cases).

3 years ago

Journal

PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • ETV6 (ETS Variant Transcription Factor 6)

PDGFRA fusion

imatinib

over3years

FIP1L1-PDGFRA-Associated Hypereosinophilic Syndrome as a Treatable Cause of Watershed Infarction. (PubMed, Stroke)

F/P+ clonal hypereosinophilic syndrome is a diagnosis to consider in patients with unexplained ischemic stroke and hypereosinophilia (especially in the setting of multiple cortical borderzone distribution) and warrants prompt initiation of imatinib.

over 3 years ago

Journal

PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • FIP1L1 (Factor Interacting With PAPOLA And CPSF1)

FIP1L1-PDGFRA fusion • PDGFRA fusion

imatinib

over3years

[VIRTUAL] An interesting case highlighting the need to test for JAK2 fusions (BSH 2021)

The patient was initially treated with hydroxycarbamide pending approval for ruxolitinib whilst being worked up for allogeneic stem cell transplant...JAK2 fusions are thought to be associated with a more aggressive clinical course than other chronic myeloid malignancies, and as such allogeneic stem cell transplant is considered the most appropriate treatment where possible, with ruxolitinib being utilised as a bridge to transplant, by improving remission rate prior to the transplantation. Given the distinct clinical and pathological characteristics, as illus- trated in this case, we believe testing for a JAK2 fusions should be considered in otherwise unclassifiable myeloid / lymphoid neoplasms, especially those with eosinophilia.

over 3 years ago

Clinical

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • JAK2 (Janus kinase 2) • TET2 (Tet Methylcytosine Dioxygenase 2) • ETV6 (ETS Variant Transcription Factor 6) • CD34 (CD34 molecule) • FIP1L1 (Factor Interacting With PAPOLA And CPSF1) • PCM1 (Pericentriolar Material 1)

PDGFRA mutation • KIT D816V • FIP1L1-PDGFRA fusion • JAK2 V617F • CD34 positive • BCR-JAK2 fusion • JAK2 fusion • PDGFRA fusion

Jakafi (ruxolitinib) • hydroxyurea