- In the majority of cases, the exact cause of ALL is unknown. However, adult patients with certain chromosome abnormalities or gene mutations have a higher chance of developing ALL:
- Philadelphia chromosome – also called BCR-ABL1 chromosome.
- This special chromosome is the result of the swapping over and fusion of sections of DNA between chromosome 22 (BCR) and chromosome 9 (ABL1), resulting in a new fusion gene called BCR‑ABL1 (Figure 3).
Figure 3 Formation of the Philadelphia chromosome BCR-ABL1
Source: Leukaemia Care
- Occurs in around 20% to 30% of patients with ALL (Fielding 2010), but does not run in families.
- Its occurrence increases with age and has been reported to be as high as 50% in patients of 60 years of age or older.
BCR-ABL1-like chromosome
- Patients with BCR-ABL1-like ALL do not have the BCR-ABL1 chromosome, but have other gene abnormalities that are similar to BCR‑ABL1.
- The combination of their gene abnormalities make these patients at high-risk of relapse of the ALL and decreased survival.
- BCR ABL1-like chromosome is seen in 20‑30% in adults with ALL.
- Other chromosomes abnormalities and gene mutations – Patients who do not have the Philadelphia chromosome or the BCR‑ABL1-like chromosome, normally have other chromosome abnormalities for example t(4;11), t(1;19) or t(12;21) or gene mutations such as CRLF2, NOTCH1 or FBW7 which are thought to be related to their ALL. These chromosomes abnormalities and gene mutations explain the different risks for patients (Table 2).
- Genetic syndromes such as Down’s syndrome, Fanconi anaemia, Klinefelter syndrome and ataxia‑telangiectasia have been linked to ALL in 5% of patients.
Table 2 Genetic abnormalities predictive of standard and high-risk ALL
| Genetic abnormalities | Standard-risk ALL Good prognosis |
High-risk ALL Poor prognosis |
| Translocation* | t(12;21), t(1,19), t(10,14) | t(4;11), t(1;19) and t(8;14) |
| Deletion** | del(6q), del(7p) and del(17) | |
| Gene mutations | NOTCH-1 or FBXW7 | CRLF2 |
| Abnormal chromosome | ETV6-RUNX1 | Philadelphia chromosome BCR-ABL1 |
| BCR-ABL1-like chromosome | ||
| ETP-ALL (early thymic precursor T-cell ALL) chromosome | ||
| Complex chromosome abnormalities |
*A chromosome translocation is the transfer of one part of a chromosome to another part of the same or a different chromosome, resulting in rearrangement of the genes.
**A chromosome deletion is when part, or the whole chromosome, is deleted.
- Other factors known to increase the risk of developing ALL include:
- Age – Increasing age, older than 70 years.
- Gender – Men are marginally more likely than women to develop adult ALL with a ratio of 1.4 to 1.
- Race – ALL occurs three times as frequently in White populations than in Black populations. White populations include patients of Hispanic ethnicity who have the highest incidence of ALL which is thought to be due to their genetic profiles.
- Association with viruses
- The Epstein-Barr virus which causes glandular fever has been connected to B‑cell ALL.
- T‑lymphotropic virus type 1 is linked with T-cell ALL (Paul et al 2016).
- Environment – Some chemicals and high levels of radiation may increase the chance of leukaemia developing. However, new strict rules limiting occupational exposure has decreased this as a cause of ALL in the UK.
- Previous cancer treatment – Patients who received chemotherapy or radiotherapy previously may develop ALL. This is called therapy‑related leukaemia, but it is relatively uncommon.
