Lymphoblasts of acute lymphoblastic leukemia origin reappeared in a male patient 34 years after the initial diagnosis. Comparison of DNA profiles of the initial and reappeared lymphoblasts revealed a partially identical sequence, indicating the possibility that these lymphoblasts may have been present as preleukemic stem cells at the time of diagnosis and remained dormant for a long period until additional events conferred proliferative activity to these dormant preleukemic stem cells. Thus, in some cases of very late relapse, the reappearance of lymphoblasts may not be due to the relapse of the original leukemic clone, but to a clonal progression of a pre-existing subclone derived from preleukemic stem cells.
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http://dx.doi.org/10.1007/s12185-013-1289-9 | DOI Listing |
Sci Transl Med
January 2025
Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
Familial platelet disorder (FPD) is associated with germline mutations, establishing a preleukemic state and increasing the risk of developing leukemia. Currently, there are no intervention strategies to prevent leukemia progression. Single-cell RNA sequencing ( = 10) combined with functional analysis of samples from patients with -FPD ( > 75) revealed that FPD hematopoietic stem and progenitor cells (HSPCs) displayed increased myeloid differentiation and suppressed megakaryopoiesis because of increased activation of prosurvival and inflammatory pathways.
View Article and Find Full Text PDFbioRxiv
October 2024
Department of Medicine, Division of Hematology, Cancer Institute, and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University; Stanford, CA, 94305, USA.
Semin Hematol
December 2024
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address:
Inflammation is a key driver of the progression of preleukemic myeloid conditions, such as clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS), to myelodysplastic syndromes (MDS). Inflammation is a critical mediator in the complex interplay of the genetic, epigenetic, and microenvironmental factors contributing to clonal evolution. Under inflammatory conditions, somatic mutations in TET2, DNMT3A, and ASXL1, the most frequently mutated genes in CHIP and CCUS, induce a competitive advantage to hematopoietic stem and progenitor cells, which leads to their clonal expansion in the bone marrow.
View Article and Find Full Text PDFLeukemia
January 2025
Division of Oncology, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope Way, Salt Lake City, UT, 84112, USA.
Leukemias arise from recurrent clonal mutations in hematopoietic stem/progenitor cells (HSPCs) that cause profound changes in the bone marrow microenvironment (BMM) favoring leukemic stem cell (LSC) growth over normal HSPCs. Understanding the cross talk between preleukemic mutated HSPCs and the BMM is critical to develop novel therapeutic strategies to prevent leukemogenesis. We hypothesize that preleukemic-LSCs (pLSCs) induce BMM changes critical for leukemogenesis.
View Article and Find Full Text PDFCancer Res
December 2024
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Tianjin Key Laboratory of Cell Therapy for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Metabolism plays a key role in the maintenance of normal hematopoietic stem cells (HSC) and in the development of leukemia. A better understanding of the metabolic characteristics and dependencies of preleukemic cells could help identify potential therapeutic targets to prevent leukemic transformation. As AML1-ETO, one of the most frequent fusion proteins in acute myeloid leukemia that is encoded by a RUNX1::RUNX1T1 fusion gene, is capable of generating preleukemic clones, in this study, we used a conditional Runx1::Runx1t1 knockin mouse model to evaluate preleukemic cell metabolism.
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