Acute myeloid leukemia (AML) is a complex and heterogeneous group of aggressive hematopoietic stem cell disease. The presence of diverse and functionally distinct populations of leukemia cells within the same patient's bone marrow or blood poses a significant challenge in diagnosing and treating AML. A substantial proportion of AML patients demonstrate resistance to induction chemotherapy and a grim prognosis upon relapse. The rapid advance in next generation sequencing technologies, such as single-cell RNA-sequencing (scRNA-seq), has revolutionized our understanding of AML pathogenesis by enabling high-resolution interrogation of the cellular heterogeneity in the AML ecosystem, and their transcriptional signatures at a single-cell level. New studies have successfully characterized the inextricably intertwined interactions among AML cells, immune cells and bone marrow microenvironment and their contributions to the AML development, therapeutic resistance and relapse. These findings have deepened and broadened our understanding the complexity and heterogeneity of AML, which are difficult to detect with bulk RNA-seq. This review encapsulates the burgeoning body of knowledge generated through scRNA-seq, providing the novel insights and discoveries it has unveiled in AML biology. Furthermore, we discuss the potential implications of scRNA-seq in therapeutic opportunities, focusing on immunotherapy. Finally, we highlight the current limitations and future direction of scRNA-seq in the field.
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http://dx.doi.org/10.3389/fonc.2024.1365330 | DOI Listing |
Mol Biol Rep
January 2025
Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Introduction: Hematologic malignancies, originating from uncontrolled growth of hematopoietic and lymphoid tissues, constitute 6.5% of all cancers worldwide. Various risk factors including genetic disorders and single nucleotide polymorphisms play a role in the pathogenesis of hematologic malignancies.
View Article and Find Full Text PDFVenetoclax plus azacitidine represents a key advance for older, unfit patients with acute myeloid leukemia (AML). The chemotherapy and venetoclax in elderly AML trial (CAVEAT) was first to combine venetoclax with intensive chemotherapy in newly diagnosed patients ≥65 years. In this final analysis, 85 patients (median age 71 years) were followed for a median of 41.
View Article and Find Full Text PDFClin Epigenetics
January 2025
School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, 2308, Australia.
Background: Hypomethylating agents (HMA), such as azacytidine (AZA) and decitabine (DAC), are epigenetic therapies used to treat some patients with acute myeloid leukaemia (AML) and myelodysplastic syndrome. HMAs act in a replication-dependent manner to remove DNA methylation from the genome. However, AML cells targeted by HMA therapy are often quiescent within the bone marrow, where oxygen levels are low.
View Article and Find Full Text PDFDrug Resist Updat
January 2025
Loma Linda University Cancer Center, Loma Linda, CA 92354, United States; Department of Basic Sciences, Loma Linda University, Loma Linda, CA 92354, United States. Electronic address:
Chromosomal rearrangements (CR) initiate leukemogenesis in approximately 50 % of acute myeloid leukemia (AML) patients; however, limited targeted therapies exist due to a lack of accurate molecular and genetic biomarkers of refractory mechanisms during treatment. Here, we investigated the pathological landscape of treatment resistance and relapse in 16 CR-AML patients by monitoring cytogenetic, RNAseq, and genome-wide changes among newly diagnosed, refractory, and relapsed AML. First, in FISH-diagnosed KMT2A (MLL gene, 11q23)/AFDN (AF6, 6q27)-rearrangement, RNA-sequencing identified an unknown CCDC32 (15q15.
View Article and Find Full Text PDFInvest Radiol
January 2025
From the Department of Radiology, Stanford University, Stanford, CA (K.W., M.J.M., A.M.L., A.B.S., A.J.H., D.B.E., R.L.B.); Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA (K.W.); GE HealthCare, Houston, TX (X.W.); GE HealthCare, Boston, MA (A.G.); and GE HealthCare, Menlo Park, CA (P.L.).
Objectives: Pancreatic diffusion-weighted imaging (DWI) has numerous clinical applications, but conventional single-shot methods suffer from off resonance-induced artifacts like distortion and blurring while cardiovascular motion-induced phase inconsistency leads to quantitative errors and signal loss, limiting its utility. Multishot DWI (msDWI) offers reduced image distortion and blurring relative to single-shot methods but increases sensitivity to motion artifacts. Motion-compensated diffusion-encoding gradients (MCGs) reduce motion artifacts and could improve motion robustness of msDWI but come with the cost of extended echo time, further reducing signal.
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