We hereby report a case of acute myeloid leukemia with translocation t(2;3) and involvement of the ectopic virus integration site-1 (EVI1) gene. Like most other 3q26-related disorders reported thus far, we describe a phenotype with elevated platelet counts and dysmegakaryopoesis. The clinical course of our patient was complicated by symptomatic thrombophilia and chemoresistance. In addition, our case exhibited FLT3 (Fms-related tyrosine kinase 3) internal tandem duplication. Although anagrelide was successful in controlling elevated platelet counts, allogeneic stem cell transplantation failed to overcome chemoresistance due to simultaneous graft-versus-host-disease and relapse of acute myeloid leukemia. Given the dismal outcome of our case and previously reported cases, we propagate the implementation of targeted therapies to newly diagnosed patients with acute myeloid leukemia t(2;3). Preclinical models indicate drugs that plausibly target the EVI1-related molecular vulnerability as candidates for basket trials. Anagrelide exhibited a hopeful signal of activity in 3q26-related thrombocytosis and should be evaluated for implementation as supportive care.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144280 | PMC |
| http://dx.doi.org/10.3960/jslrt.56.64 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
HemaScope: A Tool for Analyzing Single-cell and Spatial Transcriptomics Data of Hematopoietic Cells.
Genomics Proteomics Bioinformatics
January 2025
Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Research Unit of Hematologic Malignancies Genomics and Translational Research of Chinese Academy of Medical Sciences, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) techniques hold great value in evaluating the heterogeneity and spatial characteristics of hematopoietic cells within tissues. These two techniques are highly complementary, with scRNA-seq offering single-cell resolution and ST retaining spatial information. However, there is an urgent demand for well-organized and user-friendly toolkits capable of handling single-cell and spatial information.
View Article and Find Full Text PDFA Simple Machine Learning-Based Quantitative Structure-Activity Relationship Model for Predicting pIC Inhibition Values of FLT3 Tyrosine Kinase.
Pharmaceuticals (Basel)
January 2025
Centro de Química Médica, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago 7780272, Chile.
Acute myeloid leukemia (AML) presents significant therapeutic challenges, particularly in cases driven by mutations in the FLT3 tyrosine kinase. This study aimed to develop a robust and user-friendly machine learning-based quantitative structure-activity relationship (QSAR) model to predict the inhibitory potency (pIC values) of FLT3 inhibitors, addressing the limitations of previous models in dataset size, diversity, and predictive accuracy. Using a dataset which was 14 times larger than those employed in prior studies (1350 compounds with 1269 molecular descriptors), we trained a random forest regressor, chosen due to its superior predictive performance and resistance to overfitting.
View Article and Find Full Text PDFEvaluation of 3D-Printed Microfluidic Structures for Use in AML-Specific Biomarker Detection of PML::RARA.
Int J Mol Sci
January 2025
Department Hamm 1, Hamm-Lippstadt University of Applied Science, 59063 Hamm, Germany.
An obstacle for many microfluidic developments is the fabrication of its structures, which is often complex, time-consuming, and expensive. Additive manufacturing can help to reduce these barriers. This study investigated whether the results of a microfluidic assay for the detection of the promyelocytic leukemia (PML)-retinoic acid receptor α (RARα) fusion protein (PML::RARA), and thus for the differential diagnosis of acute promyelocytic leukemia (APL), could be transferred from borosilicate glass microfluidic structures to additively manufactured fluidics.
View Article and Find Full Text PDFLipopolymers as the Basis of Non-Viral Delivery of Therapeutic siRNA Nanoparticles in a Leukemia (MOLM-13) Model.
Biomolecules
January 2025
Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB T6G 1R1, Canada.
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 for delivering siRNA molecules is imperative due to the challenges involved in effectively delivering the siRNA into cells. We investigated the delivery of siRNA to AML MOLM-13 cells with the use of two lipid-substituted polyethyleneimines (PEIs), a commercially available reagent (Prime-Fect) and a recently reported reagent with improved lipid substitution (PEI1.
View Article and Find Full Text PDFCalreticulin-From the Endoplasmic Reticulum to the Plasma Membrane-Adventures of a Wandering Protein.
Cancers (Basel)
January 2025
Department of Pathology, Dalhousie University, Halifax, NS B3H 1X5, Canada.
Calreticulin (CRT) is a 46 kDa highly conserved protein initially identified as calregulin, a prominent Ca-binding protein of the endoplasmic reticulum (ER). Subsequent studies have established that CRT functions in the ER's protein folding response and Ca homeostatic mechanisms. An ER retention signal on the carboxyl terminus of CRT suggested that CRT was restricted to the ER.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!