Inflammation drives pressure on TP53 mutant clones in myeloproliferative neoplasms

Article Genetics & Heredity

Single-cell multi-omics identifies chronic inflammation as a driver of TP53-mutant leukemic evolution

Alba Rodriguez-Meira et al.

Summary: This study analyzes hematopoietic stem/progenitor cells from patients with secondary acute myeloid leukemia (sAML) transforming from myeloproliferative neoplasm. They find that chronic inflammation suppresses TP53 wild-type cells while enhancing the fitness advantage of TP53-mutant cells, promoting genetic evolution. These findings will aid in the development of risk-stratification, early detection, and treatment strategies for TP53-mutant leukemia.

NATURE GENETICS (2023)

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Article Hematology

Inflammation and myeloid malignancy: quenching the flame

Ryan J. Stubbins et al.

Summary: Chronic inflammation with aging, known as inflammaging, plays a significant role in the development of myeloid malignancies. Aberrant inflammatory activity affects various cells in the bone marrow, including normal blood and stromal cells, as well as leukemic cells, in distinct ways. Inflammation can selectively promote the clonal expansion of malignant cells by suppressing normal hematopoietic cells through immune-mediated mechanisms. Understanding the intrinsic and extrinsic effects of inflammation provides insights for future clinical trials.

BLOOD (2022)

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Article Hematology

Primary myelofibrosis: 2021 update on diagnosis, risk-stratification and management

Ayalew Tefferi

Summary: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by stem cell-derived clonal myeloproliferation, with common features including bone marrow fibrosis, abnormal inflammatory cytokine expression, anemia, hepatosplenomegaly, etc. Diagnosis is primarily based on bone marrow morphology. Treatment strategies can vary based on risk stratification, with options such as observation, drug therapy, or hematopoietic stem cell transplant.

AMERICAN JOURNAL OF HEMATOLOGY (2021)

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Article Cell & Tissue Engineering

Reconstructing the Lineage Histories and Differentiation Trajectories of Individual Cancer Cells in Myeloproliferative Neoplasms

Debra Van Egeren et al.

Summary: The JAK2-V617F mutation affects the self-renewal and differentiation dynamics of HSCs in MPNs patients, helping to reconstruct cancer lineages, with the mutation likely occurring several decades before diagnosis and providing a selective advantage for mutant HSCs.

CELL STEM CELL (2021)

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Review Hematology