Chromosomal translocations

Translocations, which involve the transfer of DNA between chromosomes, are found in many of the hematological malig nancies. Other chromosomal abnormalities include chromosomal deletions and inversions. Table 6.2 shows some of the translocations described in myeloid and lymphoid malignancies. As a result of chromosomal translocation, a gene from one chromosome ends up adjacent to a gene on the chromosome to which the DNA has been translocated, and this may have important consequences for the cell (and the patient). If a potentially cancerous gene (proto-oncogene), which is generally not transcriptionally active, abuts onto a gene that is being actively transcribed, this may result in upregulation of expression of that proto-oncogene. This is exactly the situation in many translocations described to date. In some cases, such as the translocation between chromosomes 14 and 18 found in many cases of follicular lymphoma, the BCL-2 gene is moved to chromosome 14 and comes under the transcriptional control of the immunoglobulin heavy chain (IgH) gene, which is transcribed actively. The increase in BCL-2 protein prevents apoptosis (programmed cell death) and this may explain, in part, the underlying pathogenesis of some lymphomas.

The first non-random chromosome translocation described was the Philadelphia chromosome, in which recip

Table 6.2 PCR-amplifiable chromosomal translocations and gene rearrangements in human hematological disorders.

Disease

Translocation

Genes involved

Acute myeloid leukemia

M2

t(8;21)

ETO-AML1

M2 or M4

t(6;9)

DEK-CAN

M3

t(15;17)

PML-RARa

M4

inv(16)

CBFP-MYH11

Acute lymphoblastic leukemia

B-lineage

t(9;22)

BCR-ABL

t(1;19)

E2A-PBX1

t(17;19)

HLF-E2A

t(12;21)

TEL-AML-1

t(4;11)

AF4-MLL

t(8;14)

MYC-IgH

T-lineage

TAL interstitial deletion

TAL

t(1;14)

TAL-1-TCR6

t(10;14)

HOX11-TCRa

t(11;14)

11p13-TCR8

Lymphomas

Follicular and diffuse NHL

t(14;18)

BCL-2-IgH

Mantle cell lymphoma

t(11;14)

BCL-1-IgH

Burkitt's lymphoma

t(8;14)

MYC-IgH

Anaplastic lymphoma

t(2;5)

ALK-NPM

Gene rearrangements

Immunoglobulin heavy chain

B-cell lymphoma/leukemia

T-cell receptors

T-cell lymphoma/leukemia

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