In contrast to solid cancers, which often require genetic modifications and complex cellular reprogramming for effective metastatic dissemination, leukaemic cells uniquely possess the innate ability for migration and invasion. Dedifferentiated, malignant leukocytes retain the benign leukocytes’ capacity for cell motility and survival in the circulation, while acquiring the potential for rapid and uncontrolled cell division. For these reasons, leukaemias, although not traditionally considered as metastatic diseases, are in fact models of highly efficient metastatic spread. Accordingly, they are often aggressive and challenging diseases to treat. In this Perspective, we discuss the key molecular processes that facilitate metastasis in a variety of leukaemic subtypes, the clinical significance of leukaemic invasion into specific tissues and the current pipeline of treatments targeting leukaemia metastasis.
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The authors thank A. Chenn and P. Islam for their discussions and careful review of the manuscript. The authors apologize to all colleagues whose work could not be discussed owing to space limitations.
The authors have received research funding from Bayer Pharmaceutical and Glycomimetics, Inc.
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- Choroid plexus
A secretory tissue in the brain that produces cerebrospinal fluid.
The process of extravasating out of a vessel into the surrounding stroma.
- Endosteal niche
The niche in the bone marrow adjacent to the bone lining (endosteum).
- Germinal centre
Site within the spleen and lymph node where B cells proliferate and differentiate.
- High endothelial venules
(HEVs). Specialized post-capillary venules in the lymph node that allow for the trafficking of immune cells in and out of this lymphoid organ.
- Intravital microscopy
High-resolution imaging of a living organism to study biological events at the cellular level.
The inner two meningeal layers that surround the brain and spinal cord and contain cerebrospinal fluid.
- Minimal residual disease
(MRD). A subclinical amount of disease remaining after therapy that can fuel relapse.
- Nurse-like cells
Monocyte-derived cells that support the survival and growth of chronic lymphocytic leukaemia.
- Sinusoidal vessels
Large vessels found in the bone marrow, spleen, lymph node and liver that contain fenestrations allowing the trafficking of cells across the vascular endothelium.
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Whiteley, A.E., Price, T.T., Cantelli, G. et al. Leukaemia: a model metastatic disease. Nat Rev Cancer (2021). https://doi.org/10.1038/s41568-021-00355-z