Genetic factors play a significant role in the etiology of ALL:
- Karyotypic abnormalities in the leukemic cells of children with ALL
- Increased risk of ALL in children with constitutional chromosomal abnormalities
- Familial leukemia
- High incidence of leukemia in identical twins
- Molecular epidemiological evidence - various alleles of specific genes important
Summary of Genetic etiological factors associated ALL:
| Genetic Factor |
|
|
Constitutional chromosomal abnormality |
Down syndrome
(Trisomy 21) |
- 2.1% incidence by age 5
- Increased risk AML or ALL (15 - 20X increased risk of normal)
- Cure rates higher than general population in AML
- Cure rates worse for ALL than general population - possibly due to treatment related toxicity
- Modifications now in place for T-21 patients
|
Neurofibromatosis
type I |
|
| Fanconi anemia |
- Autosomal recessive
- Increased chromosomal fragility
- Defective replication and repair of DNA
|
| Bloom syndrome |
- Autosomal recessive
- Increased chromosomal fragility
- Defective replication and repair of DNA
|
| Shwachman Diamond |
|
| Ataxia-Telangiectasia |
- Autosomal recessive
- Increased chromosomal fragility
- T cell ALL common
|
| Immunodeficiency Syndromes |
Congenital Immunodeficiency Syndromes |
|
| Familial Risk |
Multiple studies show increased risk of ALL within families |
- Frequency of leukemia is higher than expected in the family of a patient with leukemia
|
- Identical twins - high concordance rate among younger identical twins - as high as 25% in infancy
|
Genetic changes |
In utero genetic events |
- Concordance studies with twins
|
- Leukemogenic translocations found in a patient`s leukemic clone cells can be detected in minor hematopoetic populations at birth
|
- Studies of stored cord blood and blood samples show that as many as 1 in 100 to 1 in 1000 newborns have preleukemic translocations. Most don`t go on to develop leukemia
|
