Unraveling the Molecular Drivers of Disease Progression in Myeloid Malignancies

Myeloid malignancies, including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs), arise from disruptions in normal hematopoiesis, the finely tuned developmental process generating blood cells from hematopoietic stem and progenitor cells (HSPCs). Despite advances in diagnostics and therapies, disease progression and relapse remain significant challenges, underscoring the urgent need to unravel the cellular and molecular mechanisms underlying these malignancies.

The progression of myeloid diseases involves genetic and epigenetic alterations that perturb normal cell fate decisions, differentiation pathways, and stem cell self-renewal capacities. Mutations in genes controlling chromatin structure (e.g., ASXL1, EZH2), transcriptional regulators (e.g., RUNX1, CEBPA), and splicing factors (e.g., SF3B1, SRSF2) not only initiate disease but also drive clonal evolution and therapy resistance. Importantly, these alterations impact developmental programs, leading to the expansion of immature progenitor cells, blocked differentiation, and the acquisition of aggressive phenotypes.
Recent advances in single-cell genomics, spatial transcriptomics, and lineage tracing have illuminated how malignant clones disrupt normal cell hierarchies and remodeling of the bone marrow niche. Aberrant cell-cell interactions and signals from the microenvironment further promote disease progression and immune evasion. Understanding these developmental missteps at the molecular and cellular level offers promising avenues for identifying biomarkers of progression and developing targeted therapies to restore normal differentiation and hematopoietic balance.

This Research Topic aims to integrate insights from molecular biology, cell biology, and developmental biology to shed light on the complex drivers of disease progression in myeloid malignancies and inspire innovative therapeutic strategies.
Key areas of interest include:
• Genetic mutations affecting hematopoietic cell fate and differentiation
• Epigenetic changes altering developmental gene programs
• Dysregulation of transcription factors controlling lineage commitment
• Aberrant stem cell self-renewal and differentiation blockades
• Single-cell and spatial analyses of developmental hierarchies
• Clonal dynamics and lineage tracing during disease evolution
• Microenvironmental cues influencing developmental pathways

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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Technology and Code

Keywords: Myeloid malignancies, Acute Myeloid Leukemia, Myelodysplastic Syndrome

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