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The spatial landscape of cancer hallmarks reveals patterns of tumor ecological dynamics and drug sensitivity.
Cell Rep
January 2025
Josep Carreras Leukaemia Research Institute (IJC), Badalona, Spain; Barcelona Supercomputing Center (BSC), Barcelona, Spain. Electronic address:
Tumors are complex ecosystems of interacting cell types. The concept of cancer hallmarks distills this complexity into underlying principles that govern tumor growth. Here, we explore the spatial distribution of cancer hallmarks across 63 primary untreated tumors from 10 cancer types using spatial transcriptomics.
View Article and Find Full Text PDFLongitudinal omics data and preclinical treatment suggest the proteasome inhibitor carfilzomib as therapy for ibrutinib-resistant CLL.
Nat Commun
January 2025
Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Chronic lymphocytic leukemia is a malignant lymphoproliferative disorder for which primary or acquired drug resistance represents a major challenge. To investigate the underlying molecular mechanisms, we generate a mouse model of ibrutinib resistance, in which, after initial treatment response, relapse under therapy occurrs with an aggressive outgrowth of malignant cells, resembling observations in patients. A comparative analysis of exome, transcriptome and proteome of sorted leukemic murine cells during treatment and after relapse suggests alterations in the proteasome activity as a driver of ibrutinib resistance.
View Article and Find Full Text PDFReal World Evidence From 2 Decades of First-Line TKI Therapy in Chronic Myeloid Leukemia (CML): Insights From ACHO's RENEHOC Registry.
Clin Lymphoma Myeloma Leuk
December 2024
Clinica IMAT Oncomedica Auna S.A.S, Montería, Colombia.
Background: Chronic myeloid leukemia (CML) treatment has significantly evolved with the introduction of tyrosine kinase inhibitors. However, access to these treatments and outcomes vary globally. This study examines 2 decades of CML management in Colombia using the RENEHOC registry, focusing on TKI efficacy, safety, and healthcare system challenges.
View Article and Find Full Text PDFThe recent advance of PROTACs targeting BCR-ABL for the treatment of chronic myeloid leukemia.
Bioorg Chem
January 2025
Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou 450018 China. Electronic address:
The chronic myeloid leukemia is a malignant hematopoietic disorder in which the BCR-ABL kinase has been identified as the causative protein. The inhibitors targeting BCR-ABL kinase have been extensively employed in clinical management of chronic myeloid leukemia, significantly enhancing survival rates and prognosis for patients. Despite the extensive utilization of 1st to 4th generation BCR-ABL inhibitors in clinical therapy, the emergence of drug-resistant mutations necessitates an urgent quest for novel therapeutic strategies.
View Article and Find Full Text PDFHemaScope: 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.
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