Joseph Brandwein
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View article: Suppressing t(4;11) Acute Leukemia by Lipopolymer Nanoparticle Delivery of siRNA Targeting <i>KMT2A::AFF1</i> with Enhanced Extrahepatic Delivery
Suppressing t(4;11) Acute Leukemia by Lipopolymer Nanoparticle Delivery of siRNA Targeting <i>KMT2A::AFF1</i> with Enhanced Extrahepatic Delivery Open
Effective siRNA delivery in acute lymphoblastic leukemia (ALL) is limited by preferential hepatic accumulation. To address this, a lipopolymer (PEI‐C) is developed by conjugating lipid to polyethylenimine and formulated lipopolymer nanopar…
View article: Lipopolymers as the Basis of Non-Viral Delivery of Therapeutic siRNA Nanoparticles in a Leukemia (MOLM-13) Model
Lipopolymers as the Basis of Non-Viral Delivery of Therapeutic siRNA Nanoparticles in a Leukemia (MOLM-13) Model Open
Small interfering RNA (siRNA) therapy in acute myeloid leukemia (AML) is a promising strategy as the siRNA molecule can specifically target proteins involved in abnormal cell proliferation. The development of a clinically applicable method…
View article: Figure S4 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Figure S4 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells Open
Supplementary Figure S4: Expression of NMT1 and NMT2 as it associates with AML risk factors. Patients were separated based on mutational status of commonly used prognostic genes and compared based on expression of NMT1 (A) and NMT2 (B). No…
View article: Figure S7 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Figure S7 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells Open
Figure S7: SFKs respond similarly to zelenirstat. AML cell lines were pre-treated with 1µM zelenirstat for 48 hours, then stimulated with 100 ng/mL SCF & FL. Levels of indicated Src-family kinases were analyzed by western blot.
View article: Figure S13 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Figure S13 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells Open
Supplementary Figure S13: Zelenirstat reduces AMPKβ. AML cell lines were treated with zelenirstat for 48 hours, then stimulated with 100 nL/mL SCF & FL, then levels of AMPKβ analyzed by western blot. Band intensity was determined using Ima…
View article: Figure S9 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Figure S9 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells Open
Supplementary Figure S9: Zelenirstat causes ER stress and Apoptosis in AML Cell Lines U937, and KG-1 cell lines were incubated with zelenirstat for up to 72 hours, then lysed and proteins analyzed by western blot. Representative blots of 3…
View article: Figure S11 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Figure S11 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells Open
Supplementary Figure S11: Zelenirstat reduces glycolytic rate in AML cells. MV-4-11 (A-B) and U937 (C-D) cells were incubated with zelenirstat for 48 hours, then extracellular acidification assessed using an Aglient Seahorse and Glycolytic…
View article: Data from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Data from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells Open
Acute myeloid leukemia (AML) is a hematologic malignancy with limited treatment options and a high likelihood of recurrence after chemotherapy. We studied N-myristoylation, the myristate modification of proteins linked to survival signalin…
View article: Figure S10 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Figure S10 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells Open
Supplementary Figure S10: Zelenirstat reduces OCR in U937 cells U937 cells were incubated with zelenirstat for 48 hours then analyzed using an Agilent Seahorse and Glycolytic Rate Assay kit (n = 5).
View article: Figure S3 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Figure S3 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells Open
Supplementary Figure S3: NMT2 is associated with overall survival in the GSE37642 dataset: Patients in the GSE37642 dataset were separated into quartiles based on NMT2 expression, and overall survival analyzed via Kaplan-Meier plots. Curve…
View article: Figure S5 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Figure S5 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells Open
Supplementary Figure S5: MISS-54 Scores Categorized by AML Risk Category TCGA-LAML patients were separated into groups by ELN2022 risk classification (A) or TCGA-LAML molecular risk category (B) and MISS-54 scores of groups compared by one…
View article: Figure S2 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Figure S2 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells Open
Supplementary Figure S2: Zelenirstat effectively inhibits myristoylation in AML cells. Cells pre-incubated with zelenirstat at indicated concentrations for 1 hour were metabolically labeled with alkynyl-myristate analog. Incorporation of a…
View article: Figure S12 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Figure S12 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells Open
Supplementary Figure S12: Matched viability assay for Resipher assays Cells were plated under identical conditions to Resipher assays in fig6D and viability measured by CellTitre BlueTM at 24 hours intervals (n = 2). No significant loss of…
View article: Figure S6 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Figure S6 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells Open
Supplementary Figure S6: Zelenirstat causes manageable weight loss in mice. Body weight of mice in xenograft experiments fig3C (A) and fig3D (B). High-dose zelenirstat caused weight loss that was rapidly recovered after cessation of treatm…
View article: Figure S8 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Figure S8 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells Open
Figure S8: Zelenirstat disrupts signalling in AML. U937 and KG-1 cells were incubated with zelenirstat for 48 hours, stimulated with 100 ng/mL FL & SCF, then lysed. Lysates were probed for HCK, phosphorylated SFKs, and phosphorylated Stat5…
View article: FIgure S1 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
FIgure S1 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells Open
Supplementary Figure S1: NMT1 and NMT2 have distinct expression patterns. NMT1 is consistently expressed in ∼1 400 CCLE cell lines and ∼11 000 TCGA patient samples. NMT2 is more variable and entirely absent in some cells. Expression measur…
View article: Supplementary Data from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Supplementary Data from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells Open
Table of Materials
View article: Figure S14 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Figure S14 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells Open
Supplementary Figure S14: Zelenirstat shows promising synergy with venetoclax. AML cell lines were screened for synergy between zelenirstat and venetoclax using Horizon’s Combination Profiling platform. Isobolograms of (A) MV-4-11 and (B) …
View article: Real-World Experience with CPX-351 for Secondary Acute Myeloid Leukemia: Comparison with FLAG-IDA in a Propensity Score Matching Analysis
Real-World Experience with CPX-351 for Secondary Acute Myeloid Leukemia: Comparison with FLAG-IDA in a Propensity Score Matching Analysis Open
CPX-351 is approved for therapy-related acute myeloid leukemia (t-AML), and AML with myelodysplastic-related changes (AML-MRC). This approval was based on improved survival, remission rates, and similar safety compared to 7+3 regimen. In c…
View article: Infectious Complications and Antibiotic Prophylaxis during Induction Therapy with Venetoclax Plus Azacitidine for Previously Untreated AML: A Real-World Experience
Infectious Complications and Antibiotic Prophylaxis during Induction Therapy with Venetoclax Plus Azacitidine for Previously Untreated AML: A Real-World Experience Open
Venetoclax + azacitidine (ven-aza) induction therapy has become the standard of care at many centers for AML patients who are unfit for intensive induction therapy. Although widely utilized, the efficacy of antimicrobial prophylaxis during…
View article: 10 Year Follow-up of CALGB 10603/Ratify: Midostaurin Versus Placebo Plus Intensive Chemotherapy in Newly Diagnosed <i>FLT3</i> Mutant Acute Myeloid Leukemia Patients Aged 18-60 Years
10 Year Follow-up of CALGB 10603/Ratify: Midostaurin Versus Placebo Plus Intensive Chemotherapy in Newly Diagnosed <i>FLT3</i> Mutant Acute Myeloid Leukemia Patients Aged 18-60 Years Open
Background: C10603/RATFIY was the first AML trial to show the benefit of adding a targeted agent to intensive chemotherapy for a specific genetically determined subset (Stone R et al, NEJM 2017). The addition of the multi-kinase inhibitor …
View article: Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells Open
Acute myeloid leukemia (AML) is a hematologic malignancy with limited treatment options and a high likelihood of recurrence after chemotherapy. We studied N-myristoylation, the myristate modification of proteins linked to survival signalin…
View article: Lipopolymer/siRNA complexes engineered for optimal molecular and functional response with chemotherapy in FLT3-mutated acute myeloid leukemia
Lipopolymer/siRNA complexes engineered for optimal molecular and functional response with chemotherapy in FLT3-mutated acute myeloid leukemia Open
Approximately 25% of newly diagnosed AML patients display an internal tandem duplication (ITD) in the fms-like tyrosine kinase 3 (FLT3) gene. Although both multi-targeted and FLT3 specific tyrosine kinase inhibitors (TKIs) are being utiliz…
View article: Lipopolymer/siRNA Nanoparticles Targeting the Signal Transducer and Activator of Transcription 5A Disrupts Proliferation of Acute Lymphoblastic Leukemia
Lipopolymer/siRNA Nanoparticles Targeting the Signal Transducer and Activator of Transcription 5A Disrupts Proliferation of Acute Lymphoblastic Leukemia Open
The therapeutic potential of small interfering RNAs (siRNAs) in gene-targeted treatments is substantial, but their suboptimal delivery impedes widespread clinical applications. Critical among these is the inability of siRNAs to traverse th…
View article: ULK2 Is a Key Pro-Autophagy Protein That Contributes to the High Chemoresistance and Disease Relapse in FLT3-Mutated Acute Myeloid Leukemia
ULK2 Is a Key Pro-Autophagy Protein That Contributes to the High Chemoresistance and Disease Relapse in FLT3-Mutated Acute Myeloid Leukemia Open
We recently demonstrated that a small subset of cells in FLT3-mutated acute myeloid leukemia (AML) cell lines exhibit SORE6 reporter activity and cancer stem-like features including chemoresistance. To study why SORE6+ cells are more chemo…
View article: An In Vitro Model for Acute Myeloid Leukemia Relapse Using the SORE6 Reporter
An In Vitro Model for Acute Myeloid Leukemia Relapse Using the SORE6 Reporter Open
Many patients diagnosed with acute myeloid leukemia (AML) relapse within two years of the initial remission. The biology of AML relapse is incompletely understood, although cancer stem-like (CSL) cells have been hypothesized to be importan…
View article: Exploring the Potential of siRNA Delivery in Acute Myeloid Leukemia for Therapeutic Silencing
Exploring the Potential of siRNA Delivery in Acute Myeloid Leukemia for Therapeutic Silencing Open
We investigated the feasibility of using siRNA therapy for acute myeloid leukemia (AML) by developing macromolecular carriers that facilitated intracellular delivery of siRNA. The carriers were derived from low-molecular-weight (<2 kDa) po…