Question

What are the genetic mutations that lead to ALL (Acute Lymphoblastic Leukemia) for T-cells and the ALL for B-cells?

Answer 1

Acute lymphoblastic leukemia (ALL) is mainly a disease of childhood that arises from recurrent genetic alterations that block precursor B- and T-cell differentiation and drive aberrant cell proliferation and survival

T cell ALL

It mainly associated with the deregulated expression of normal transcription factor proteins.

It is a result of chromosomal rearrangements juxtaposing promoter and enhancer elements of T-cell receptor genes TRA@ (14q11), TRB@ (T-cell receptor b, 7q34-35), TRG@ (T-cell receptor g, 7p15) and TRD@ (T-cell receptor d, 14q11) to important transcription factor genes.

The rearrangements are reciprocal translocations, and lead to a deregulation of transcription of the partner gene by juxtaposition with the regulatory region of one of the TCR loci .

Bcell ALL

It occurs due to the mutations such as

t(9;22) (q34;q11.2) BCR-ABL1,

t(v;11q23) MLL rearranged,

t(12;21)(p13;q22) TEL-AML1 (ETV6-RUNX1),

t(5;14)(q31;q32) IL3-IGH,

t(1;19) (q23;p13.3) E2A-PBX1 (TCF3-PBX1)