- Chromosomal abnormalities are identified in around 50% of all adult patients with AML. Although some 40-50% of AML patients have no chromosomes abnormalities, they do have other gene mutations such as the FMS Like Tyrosine Kinase 3 (FLT3) gene and the nucleophosmin 1 (NPM1) gene.
- AML genetic abnormalities, and the prognosis are shown in Table 2.
Table 2 Genetic abnormalities in AML and prognosis
|GENETIC ABNORMALITIES IN AML||PROGNOSIS|
|t(3;3) or inv (3)||Poor|
|t(15;17) in APL||Good|
|t(16;16) or inv (16)||Good|
|Deletion/abnormalities of chromosome 5 or chromosome 7||Poor|
|Complex chromosome abnormalities in 3 or more chromosomes||Poor|
|ASXL1 (Additional sex combs-like 1) gene mutation||Poor|
|FLT3-ITD (FMS‑Like Tyrosine Kinase-3 – internal tandem duplication gene mutation||Poor|
|NPM1 (nucleophosmin 1) gene mutation with/without FLT3-ITD gene mutation||Good|
|Non-mutated NPM1 with/without FLT3-ITD gene mutation||Intermediate|
|RUNX1 (RUNX Family Transcription Factor 1) gene mutation||Poor|
|RUNX1-RUNX1T1 fusion gene||Good|
|TP-53 (tumour suppressor 53) gene mutation||Poor|
Inv (3) is an inversion of a section of chromosome 3. This may be inherited or a random mutation. Chromosome inversion is where a chromosome has been broken at two separate points, rotated by 180 degrees, and re-joined within the chromosome.
- In chromosome abnormalities, the “t” stands for translocation. The numbers in brackets after the “t” are the numbers of the chromosomes involved in the translocation.
- With a translocation, one part of a chromosome is transferred to another part of the same or a different chromosome. This results in a rearrangement of the genes within the newly-formed chromosome.
- Patients with syndromes due to genetic mutations are at increased risk of AML. These include:
- Neurofibromatosis type 1 (condition where generally benign tumours grow along the nerves, causing a number of symptoms)
- Down’s syndrome (extra copy of chromosome 21)
- Trisomy 8 (extra copy of chromosome 8)