Mtcp1

?

in tumors of myeloid origin. Furthermore, there is a lineage dependency even among lymphoid malignancies for the immune loci involved. Thus, translocations involving 7q34 and 14qll are restricted to T cell malignancies (Table 2) whereas translocations that involve 2pl2, 14q32 and 22qll are specifically associated with B cell neoplasms (Table 3). Since loci 7q34 and 14qll harbor the TCR genes and in T cells these genomic loci undergo rearrangements, errors in recombination that allow interchromosomal translocations are targeted to these regions in T cells. A similar conclusion can be derived about translocations associated with the immunoglobulin genes in B cells. It is also significant that these immune loci contain powerful transcriptional regulatory sequences. The major function of a mature immune cell is to synthesize immune molecules - immunoglobulin or T cell receptors - thus, recombinase-mediated rearrangements that will erroneously juxtapose genes that are normally silent in these cells will result in the forced expression of such genes. Depending upon the nature of the gene translocated, this deregulated expression of the rearranged gene could result in various phenotypic changes. If the phenotype conferred by the deregulated expression is survival advantage, it will cause a clonal expansion of the lymphoid cells with this particular rearrangement and provide a pool of cells that are prone to

Table 3 Translocations involving immune loci in B cell neoplasms

Neoplasia Immune locus Partner locus Gene involved Deregulated oncogenic function/domain

Table 3 Translocations involving immune loci in B cell neoplasms

Neoplasia Immune locus Partner locus Gene involved Deregulated oncogenic function/domain

CLL, MM, NHL - mantle cell

14q32

11q13

Bcl-1

Cyclin

NHL - follicular

14q32

18q21

Bcl-2

Inhibitor of apoptosis

CLL, PLL

14q32

19q13

Bcl-3

Transcriptlonal/RELVNFKB

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