Patients suffering from B-ALL were analyzed for residual leukemic cells by means of the PCR technique. Using primers specific for conserved domains of each VH-family and a primer universal to the JH-regions, immunoglobulin gene fragments have been amplified from bone marrow aspirate-derived DNA in six cases of B-ALL. Cloning and sequencing of the amplified fragments revealed the usage of the VH251-family in two cases. VH-families 1 and 3 were used in one case each. One patient showed abnormal rearrangement with the participation of two JH regions. In the remaining case a VH6 germline fragment was involved in an apparently abnormal rearrangement. Based on the sequence information, clone-specific DIG-labeled probes were designed and used in subsequent nonradioactive hybridization protocols to estimate the prevalence of residual leukemic cells in the course of therapy. Five of the six cases of B-ALL could be included in the rest cell analysis. In all patients investigated, residual leukemic cells were detected, independent of whether a normal or apparently abnormal rearrangement has occurred. These findings imply that the prevalence of residual leukemic cells in B-ALL indicates a high risk of relapse.
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R Soc Open Sci
January 2025
Department of Anatomy, Kanazawa Medical University, Uchinada, Ishikawa 9200293, Japan.
Acute myeloid leukaemia (AML) is a haematologic malignancy with high relapse rates in both adults and children. Leukaemic stem cells (LSCs) are central to leukaemopoiesis, treatment response and relapse and frequently associated with measurable residual disease (MRD). However, the dynamics of LSCs within the AML microenvironment is not fully understood.
View Article and Find Full Text PDFThe significance of endogenous immune surveillance in acute lymphoblastic leukemia (ALL) remains controversial. Using clinical B-ALL samples and a novel mouse model, we show that neoantigen-specific CD4+ T cells are induced to adopt type-1 regulatory (Tr1) function in the leukemia microenvironment. Tr1s then inhibit cytotoxic CD8+ T cells, preventing effective leukemia clearance.
View Article and Find Full Text PDFCancer Sci
December 2024
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medicine, Fukuoka, Japan.
In this study, we investigated the measurable residual leukemic stem cell (MR-LSC) population after allogeneic stem cell transplantation (allo-SCT) for high-risk acute myeloid leukemia (AML), utilizing T-cell immunoglobulin mucin-3 (TIM-3) expression as a functional marker of AML leukemic stem cells (LSCs). Analysis of the CD34CD38 fraction of bone marrow cells immediately after achievement of engraftment revealed the presence of both TIM-3LSCs and TIM-3 donor hematopoietic stem cells (HSCs) at varying ratios. Genetic analysis confirmed that TIM-3 cells harbored patient-specific mutations identical to those found in AML clones, whereas TIM-3 cells did not, indicating that TIM-3CD34CD38 cells represent residual AML LSCs.
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December 2024
Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
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November 2024
Children's Cancer Institute, Lowy Cancer Research Centre, School of Clinical Medicine, UNSW Medicine & Health, UNSW Centre for Childhood Cancer Research, UNSW Sydney, Sydney, NSW 2052, Australia.
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