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What is acute lymphoblastic leukaemia (ALL)?

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Acute lymphoblastic leukaemia (ALL) affects blood-producing cells in your bone marrow.It's not exactly clear what causes ALL, but we do know it's more common in children than in adults and more common in men than women.

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Aplan, P. D., Harper, D. P., & Mrozek, K., 2009. Cytogenetics and Molecular Genetics of Acute Lymphoblastic Leukemia. Hematology/Oncology Clinics of North America [online]. 23 (5), pp. 991-1010. Available via: PMC (Accessed 29/10/206).

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Aplan, P. D., Harper, D. P., & Mrozek, K., 2009. Cytogenetics and Molecular Genetics of Acute Lymphoblastic Leukemia. Hematology/Oncology Clinics of North America [online]. 23 (5), pp. 991-1010. Available via: PMC (Accessed 29/10/206).

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Griffiths, M. & Mason, J., 2012. Molecular Diagnosis of Leukemia. Expert Review of Molecular Diagnosis [online]. 12 (5) (June), pp. 511-526. Available via: Medscape (Accessed 29/10/16).

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Griffiths, M. & Mason, J., 2012. Molecular Diagnosis of Leukemia. Expert Review of Molecular Diagnosis [online]. 12 (5) (June), pp. 511-526. Available via: Medscape (Accessed 29/10/16).

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Fluorescence in situ Hybridization

FISH provides a useful adjunct to cytogenetic analysis, its main advantage being that it does not rely on dividing cells and can therefore be performed on cells in interphase. Blood can be used if marrow is unavailable, and results can be obtained more quickly because cells do not need to be cultured. FISH is also both more sensitive than conventional cytogenetic analysis (0.5-1%) and has higher resolution (100 kb, depending on the probe), although, depending on the type of probe, caution needs to be applied to avoid false-positive and -negative results due to signal colocalization or drop-out. Laboratories should establish cut-off values for each probe set to define unambiguous positive results.

FISH uses fluorescently labeled DNA probes to locate specific sequences of interest and can thus identify structural and numeric chromosomal changes including balanced rearrangements and microdeletions. A targeted approach using a limited number of probes is usually employed to look for the most common or clinically relevant aberrations within the subtype of leukemia, so, unlike karyotype analysis, the technique does not normally provide a genome-wide assessment. The exception is multiplex FISH (M-FISH), where paints identify individual metaphase chromosomes, which can be useful in resolving complex karyotypes or poor morphology metaphase spreads where chromosomes are difficult to identify by their G-banding pattern alone.

FISH is particularly useful in the diagnosis of leukemia with cryptic cytogenetic abnormalities. One striking example of this is the t(12;21)(p13;q22) translocation resulting in an ETV6-RUNX1 gene fusion, the most frequent translocation in pediatric B-lineage ALL, which as a result of the breakpoints being relatively close to the telomeres of the short arm of chromosome 12 and the long arm of chromosome 21 is cytogenetically 'invisible'. It is, however, vital to identify this aberration for risk-adapted therapeutic protocols, as it is associated with the good risk prognostic group. The translocation can be detected using FISH or molecular techniques.

Interphase FISH is able to identify genomic aberrations in approximately 80% of CLL cases using a disease-specific panel of probes, and is particularly useful for identifying TP53 (17p13) and ATM (11q23) deletions, both being associated with poor prognosis. Interphase FISH analysis is generally considered to be superior to metaphase cytogenetic analysis in CLL owing to: the difficulties in persuading B cells to divide in culture (they divide slowly and need mitogen stimulation to produce enough metaphases for analysis); the fact that most clinically relevant aberrations in CLL are copy-number changes; the limited sensitivity of metaphase analysis such that small populations of abnormal cells may be missed; the fact that submicroscopic deletions of prognostic relevance will not be detected by conventional G-band cytogenetics; and the fact that interphase FISH is quicker than metaphase analysis and may be cheaper if limited panels of probes are used.

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fish (fluorescent in situ hybridization)

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FISH provides a useful adjunct to cytogenetic analysis, its main advantage being that it does not rely on dividing cells and can therefore be performed on cells in interphase. Blood can be used if marrow is unavailable, and results can be obtained more quickly because cells do not need to be cultured.

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Desai, P., et al., 2016. Side scatter versus CD45 flow cytometric plot can distinguish acute leukaemia subtypes. Indian Journal of Medical Resarch [online].143 (7) (October), pp. 17-22. Available via: Pubmed (Accessed 21/10/2016).

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Desai, P., et al., 2016. Side scatter versus CD45 flow cytometric plot can distinguish acute leukaemia subtypes. Indian Journal of Medical Resarch [online].143 (7) (October), pp. 17-22. Available via: Pubmed (Accessed 21/10/2016).

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Campana. D., Behm F. G., 2000. Immunophenotyping of Leukemia. Journal of Immunological Methods [online].

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Campana. D., Behm F. G., 2000. Immunophenotyping of Leukemia. Journal of Immunological Methods [online].

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General Haematology Task Force of the British Committee for Standardization in Haematology. 1994 Immunophenotyping in the diagnosis of Acute leukemias. J. Clin. Pathol. 47: 777-781.

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General Haematology Task Force of the British Committee for Standardization in Haematology. 1994 Immunophenotyping in the diagnosis of Acute leukemias. J. Clin. Pathol. 47: 777-781.

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Acute lymphoblastic leukaemia (ALL) | Acute lymphoblastic leukaemia (ALL) | Cancer Research UK

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Acute lymphoblastic leukaemia (ALL) starts from young white blood cells called lymphocytes in the bone marrow. Find out about symptoms, tests to diagnose, treatments and how to cope.