Causes
Chemoradiation- Mutations in DNA can cause the cell to be stuck in the lymphoblastic state,
constantly replicating and becoming malignant.
Genetic
Trisomy 21 (or Down’s Syndrome) – multiple copies of chromosome 21 lead to
higher risk, possibly due to mutations in JAK2 and CRLF2 genes.
T(12;21)- translocation resulting in the fusion gene TEL-AML1, cause of 25-30% of
child leukemias and is usually developed in utero, during fetal haemopoiesis
T(9;22)- translocation resulting in the fusion gene BCR-ABL, not seen in children but
is a key marker for adult ALL.
i.
ii.
iii.
Infection- Caused by human T-cell lymphotropic virus, and is responsible for the majority of
T-cell ALL cases.
T(12;21) – how does it work???
-
Causes a fusion mutation between the TEL (translocation-ets-leukaemia) gene and
the AML1 ( transcription factor) genes.
Requires additional genetic events for it to cause leukaemia so can present even a
decade after birth.
The protein it transcribes for (TEL-AML1) acts as a transcription repressor and
recruiter for other co-repressors such as histone deacetylases and NCoR.
Binds to enhancer region(TGTGGT) due to C-terminus being free for the AML1-b
species, and acts to inhibit basal activity
The N-terminal TEL helix-loop-helix region is essential for this inhibition so could be
used as a target for drug therapies.