Bloody Minded Episode 79 - Ghosts in the Machine | Basics of MDS & A Brief Look at AML
Feb 24, 2026
They explore how bone marrow goes from normal factory work to creative failure, focusing on myelodysplastic syndromes and their causes. The conversation covers clonal evolution, cytopenias and how dysplasia is recognised on films and marrow. They also outline what tests (flow, cytogenetics, molecular) reveal and give a brief look at acute myeloid leukaemia and how it relates to MDS.
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Why MDS Marrow Is Often Hypercellular
- MDS is bone marrow failure from defective maturation where marrow can be hypercellular despite peripheral cytopenias.
- Hypercellularity happens because dysfunctional clones drive overproduction of ineffective cells, creating marrow overflow and junk accumulation.
MDS Comes From Accumulated Genetic Errors
- MDS arises from accumulation of somatic mutations during stem cell replication, increasing with age.
- Prior cytotoxic therapy, smoking, benzene and germline syndromes (e.g., GATA2, SAMD9/9L) raise risk and produce more aggressive disease.
Three Stage Model Explains MDS Progression
- MDS progression follows initiation (driver mutation), expansion (clonal outgrowth), then further hits causing cytopenias or transformation.
- Driver mutations include splicing factors (SF3B1) and epigenetic regulators (TET2) that confer survival advantage.