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Biological models for leukaemia and lymphoma
1Leukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, London, UK. m.greaves@icr.ac.uk
IARC Scientific Publications
|April 2, 2004
Summary
Blood-cell cancers like leukemia arise from diverse stem cells and involve numerous genetic changes. Chromosomal translocations often initiate leukemia in utero, with postnatal factors critical for disease progression.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Blood-cell cancers, including leukemia, lymphoma, and myeloma, are highly diverse neoplasms originating from various hematopoietic and lymphoid stem cells.
- This heterogeneity suggests varied etiological mechanisms and the potential contribution of inherited genetic variations to cancer risk.
- Leukemias exhibit over 200 acquired molecular abnormalities, with prevalent ones linked to distinct biological subtypes, clinical features, and prognoses.
Purpose of the Study:
- To explore the molecular basis and natural history of blood-cell cancers.
- To investigate the role of genetic abnormalities, particularly chromosomal translocations, in the initiation and progression of leukemia.
- To understand the preclinical development of leukemia using molecular markers.
Main Methods:
- Analysis of molecular abnormalities in leukemia, including chromosomal translocations, gene deletions, and mutations.
- Utilizing chromosomal translocation-gene-rated fusion gene sequences as clone-specific markers for 'back-tracking' leukemia's preclinical history.
- Studying identical twins, neonatal blood spots, and cord blood to investigate the in utero origins and postnatal progression of leukemia.
Main Results:
- Chromosomal translocations are common in leukemia and lymphoma, often initiating the disease in utero, as evidenced by twin studies and neonatal blood analyses.
- The transition from benign to malignant status involves the accrual of additional molecular abnormalities.
- Leukemic fusion genes are found in healthy newborns at a rate exceeding the cumulative risk of leukemia, indicating postnatal factors are crucial for disease development.
Conclusions:
- Chromosomal translocations are early events in leukemia development, often occurring prenatally.
- Postnatal genetic changes and environmental exposures are critical for the progression of leukemia initiated by in utero events.
- The natural history of leukemic subtypes provides a valuable framework for molecular epidemiological research, particularly in infant and childhood acute lymphoblastic leukemia.