White-cell neoplasms: causes and translocations
- Mechanism
Leukaemias and lymphomas start with genetic accidents, often swapped chromosome pieces, helped along by genes, viruses, inflammation and past treatment.
What it is
Most white-cell neoplasms carry recurrent genetic lesions, and balanced chromosomal translocations are especially typical. They either block differentiation (transcription factor fusions) or switch on growth and survival signals (tyrosine kinases, MYC, BCL2). Several factors raise the risk: inherited genomic instability or Down syndrome, lymphotropic viruses, chronic antigen stimulation at a tissue site, earlier chemotherapy or radiation, and tobacco smoke.
Step by step
- A progenitor or lymphocyte acquires a first lesion, often a translocation or a mutation in a transcription factor or epigenetic regulator.
- Differentiation is partly blocked, so the cell keeps dividing at an immature stage.
- A second class of mutation activates signalling (tyrosine kinases, RAS pathway) or blocks apoptosis.
- Viruses or chronic antigen stimulation keep the cell population large, raising the chance of new mutations.
- Immune deficiency removes the T cells that would destroy virus-infected clones.
- A fully transformed clone expands and replaces the marrow or a lymphoid organ.
Translocations of haematolymphoid neoplasms to know
| Translocation | Genes joined | Effect | Neoplasm |
|---|---|---|---|
| t(9;22), the Philadelphia chromosome | BCR::ABL1 | Constitutive tyrosine kinase | Chronic myeloid leukaemia; a subset of B-ALL |
| t(12;21) | ETV6::RUNX1 | Abnormal transcription factor, maturation block | Childhood B-ALL (good prognosis) |
| t(14;18) | IGH::BCL2 | Anti-apoptotic BCL2 overexpressed | Follicular lymphoma |
| t(8;14) | MYC::IGH | MYC overexpressed, very fast growth | Burkitt lymphoma |
| t(11;14) | CCND1::IGH | Cyclin D1 overexpressed, G1 to S push | Mantle cell lymphoma (also some myelomas) |
| t(11;18) | BIRC3::MALT1 | Constant NF-κB activation | Gastric MALT lymphoma that no longer responds to H. pylori eradication |
| t(15;17) | PML::RARA | Retinoic acid receptor blocks maturation | Acute promyelocytic leukaemia |
Clinical notes
- Translocations are detected by karyotype, FISH or PCR and guide both diagnosis and targeted therapy (kinase inhibitors, retinoic acid).
- HTLV-1 is endemic in parts of the Colombian Pacific coast, the Caribbean basin and southern Japan.
Test yourself
Think of the answer, then tap the question to see it.
Why are translocations to the immunoglobulin heavy-chain locus so common in B-cell lymphomas?
Class switching and somatic hypermutation deliberately break and mutate DNA at that locus (through AID), so errors can join it to an oncogene.
Which virus causes adult T-cell leukaemia/lymphoma?
HTLV-1.
Which translocation underlies acute promyelocytic leukaemia?
t(15;17), forming the PML::RARA fusion gene.
Elsewhere in DurgiPedia
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Non-Hodgkin Lymphoma Treatment (PDQ®)–Patient Version (National Cancer Institute (NCI), 2026); Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version (National Cancer Institute (NCI), 2026).
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Representative model, for educational purposes only.