Acute lymphoblastic leukaemia

Date

2016

Authors

Andersson, A.
Moorman, A.V.
Harrison, C.J.
Mullighan, C.

Editors

Tosi, S.
Reid, A.G.

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Book chapter

Citation

The Genetic Basis of Haematological Cancers, 2016 / Tosi, S., Reid, A.G. (ed./s), Ch.5, pp.223-264

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Anna Andersson, Anthony V. Moorman, Christine J. Harrison, Charles Mullighan

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Abstract

In acute lymphoblastic leukaemia (ALL), genetic changes play an important role in diagnosis, whilst providing important clinical information. In about 75% of ALL, significant specific chromosomal rearrangements occur, including high hyperdiploidy (51–65 chromosomes), the translocation t(12;21)(p13;q22) (encoding ETV6‐RUNX1 , also known as TEL‐AML1 ), t(1;19)(p13;q22) (TCF3‐PBX1 or E2A‐PBX1 ), hypodiploidy (≤46 chromosomes), rearrangements of MLL at 11q23, t(9;22)(q34;q11.1)/BCR‐ABL1 , rearrangements of the immunoglobulin heavy chain (IGH@ ) and intrachromosomal amplification of chromosome 21 (iAMP21). These cytogenetic abnormalities show a variable distribution according to age. For example, there is a high predominance of MLL rearrangements in infants younger than 1 year of age. The dramatic decrease in the high hyperdiploidy and ETV6‐RUNX1 fusion after the age of 10 years is mirrored by an increase in the proportion of patients with the translocation t(9;22)(q34;q11) and IGH@ translocations into adulthood. iAMP21 occurs in older children and young adults. In view of their association with prognosis, cytogenetic subgroups are used in risk stratification for treatment. More recently described chromosomal abnormalities, for example the EBF1‐PDGFRB fusion, have shown sensitivity to tyrosine kinase inhibitors, resulting in improved outcome for these patients. The next decade will see an increased number of targeted therapies leading to more personalized treatments.

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© 2016 John Wiley & Sons Ltd

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