How fast does leukemia progress?

Leukemia, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Language: Английский

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Monitoring CH: time to move beyond VAF?

Blood, Journal Year: 2025, Volume and Issue: 145(9), P. 907 - 908

Published: Feb. 27, 2025

Language: Английский

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Clonal haematopoiesis of indeterminate potential: an emerging risk factor for type 2 diabetes and related complications

Diabetologia, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Language: Английский

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Adapting systems biology to address the complexity of human disease in the single-cell era

Nature Reviews Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Language: Английский

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Leukemogenic Kras mutation reprograms multipotent progenitors to facilitate its spread through the hematopoietic system

The Journal of Experimental Medicine, Journal Year: 2025, Volume and Issue: 222(6)

Published: March 12, 2025

Leukemia-driving mutations are thought to arise in hematopoietic stem cells (HSC), yet the natural history of their spread is poorly understood. We genetically induced within endogenous murine HSC and traced them unmanipulated animals. In contrast associated with clonal hematopoiesis (such as Tet2 deletion), leukemogenic KrasG12D mutation dramatically accelerated contribution all lineages. The acceleration was mediated by KrasG12D-expressing multipotent progenitors (MPP) that lacked self-renewal but showed increased proliferation aberrant transcriptome. deletion osteopontin, a secreted negative regulator stem/progenitor cells, delayed early expansion mutant progenitors. KrasG12D-carrying CXCR4-driven motility bone marrow, blockade CXCR4 reduced MPP vivo. Finally, therapeutic KRASG12D spared mature progeny. Thus, transforming facilitate own from reprogramming MPP, creating preleukemic state via two-component circuit.

Language: Английский

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Clonal hematopoiesis: elements associated with clonal expansion and diseases

Blood Research, Journal Year: 2025, Volume and Issue: 60(1)

Published: March 13, 2025

Abstract Clonal hematopoiesis (CH), characterized by the expansion of hematopoietic stem and progenitor cells harboring somatic mutations, has emerged as a significant age-related phenomenon with profound implications for human health. While initially recognized in 1960s, recent technological advances have revealed its complex nature widespread prevalence, affecting up to 84% individuals aged ≥ 70 years. The clinical significance CH extends beyond well-established role precursor hematological malignancies, encompassing association cardiovascular diseases, chronic kidney disease, other non-malignant disorders. This comprehensive review synthesizes current understanding CH, focusing on genetic molecular mechanisms, particularly roles commonly mutated genes such DNMT3A, TET2, ASXL1. We address emerging distinction between myeloid lymphoid their differential impacts disease progression, interplay inflammation. Special attention is given newly identified determinants clonal rates progression. also examines revolutionary concept passenger-approximated rate utility dynamics. Furthermore, we discuss therapeutic strategies targeting inflammatory pathways potential mitigating CH-associated complications. By integrating findings from genetic, molecular, studies, this provides framework systemic condition highlights promising directions interventions.

Language: Английский

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Mutated DNMT3A creates a public HLADQ- binding neoantigen on acute myeloid leukemia

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 13, 2025

Introduction Patients with acute myeloid leukemia (AML) often carry the same gene mutations. Neoantigens encoded by these mutations are attractive targets for immunotherapy. Methods We searched public human leukocyte antigen (HLA) class II-restricted neoantigens on AML using an in vitro T cell stimulation method. Peptides from 26 recurrent genetic aberrations were assessed predicted HLA II binding, and 24 long neopeptides 10 synthesized. Naive CD4 cells healthy individuals cocultured autologous dendritic pulsed neopeptides. Results Multiple clones isolated that recognized 5 different aberrations. Two of peptides, one well-known DNMT3A-R882H hotspot mutation a alternative reading frame created frameshift RUNX1 , after endogenous processing presentation lines transduced or CRISPR-Cas9-edited interest. The clone was also activated upon primary samples HLA-DQB1*06:02 -DQB1*06:03 positive patients mutation. Conclusion here identified neoantigen driver occurring 10% could become important target immunotherapy to treat -mutated AML.

Language: Английский

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Genomic Landscape of Mixed Phenotype Acute Leukemia Associated With Immunophenotypic Lineage Predominance: Impact on Diagnosis and Treatment

European Journal Of Haematology, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

ABSTRACT Objectives Mixed phenotype acute leukemia ( MPAL ) often poses challenges in diagnosis and clinical management. This is the first study to assess lineage/immunophenotype‐genotype association significance of AML ‐myelodysplasia‐related changes MR , cytogenetic abnormalities gene mutations, ‐ CG ‐Gene) classification. Methods We conducted a clinicopathologic genomic evaluation 25 cases by WHO HEM5 / ICC classification criteria, except for retaining those with ‐Gene Conditional ). Results The majority (22/25, 88%) showed distinct genotypes that overlapped lymphoblastic ALL myeloid profile ‐like was associated immunophenotypically lymphoid lineage predominance, respectively. may provide rationale develop lineage‐immunophenotypically/biologically guided therapy selection. Additionally, 64% carried ‐Gene, half which were lymphoid‐lineage predominance had molecular signatures, most these patients responded well ‐based induction regimens. These results support Conditional‐ be better diagnosed as rather than . Conclusion Genomic landscape AML‐like or ALL‐like immunophenotypic such could impact treatment decisions supporting evidence refine diagnostic criteria future studies.

Language: Английский

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The Progress of Autologous Hematopoietic Stem Cell Transplantation in the Treatment of Multiple Myeloma (Review)

Technology in Cancer Research & Treatment, Journal Year: 2025, Volume and Issue: 24

Published: March 1, 2025

Multiple myeloma (MM) is a malignant hematological disease originating from plasma cells that remains incurable. Autologous stem cell transplantation (ASCT) an important treatment method for MM. With the development of new drugs, MM patients who meet ASCT criteria has significantly improved, and median survival time increased by 8–10 years. The current consists mainly following stages: induction therapy, collection, transplantation, consolidation maintenance therapy. Even today, long-term control goal in clinical practice. In era early still results longer progression-free (PFS) currently standard young newly diagnosed multiple (NDMM) patients. Moreover, tandem can be considered with high-risk cytogenetics. This review discusses role MM, conditions patient chemotherapy regimen before conditioning regimen, timing effectiveness including salvage after transplantation.

Language: Английский

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Copy-number alterations in cell-free DNA can be transient or harbingers of clonal hematopoiesis

npj Precision Oncology, Journal Year: 2025, Volume and Issue: 9(1)

Published: March 25, 2025

Genome-wide plasma cfDNA pan-cancer screening of 1002 healthy elderly identified 15 individuals with CNAs unknown origin. Nine participants were reassessed over 3–5 years through health questionnaires, WB-MRI, and blood analyses. resolved in two cases but persisted seven mainly associated low-grade clonal mosaicism. These findings suggest may be transient or serve as early markers mosaicism, preceding clinical detection by years.

Language: Английский

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