changes in protein profiles in bortezomib applied multiple myeloma ...
changes in protein profiles in bortezomib applied multiple myeloma ...
changes in protein profiles in bortezomib applied multiple myeloma ...
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In MM, a chromosomal translocation between the immunoglobul<strong>in</strong> heavy cha<strong>in</strong><br />
gene on chromosome 14, locus q32 (14q32) and an oncogene 11q13 (cycl<strong>in</strong> D1), 4p16<br />
(FGFR3 & MMSET (Multiple Myeloma SET Doma<strong>in</strong>)), 6p21 (cycl<strong>in</strong> D3), 16q23 (c-<br />
maf), 20q11 (mafB) and 8q24 (mafA), which account for about 40% of all <strong>myeloma</strong><br />
tumors (Table 1.2), (Bergsagel and Kuehl, 2001; Barillé-Nion et al., 2003; Kyle and<br />
Rajkumar, 2004) is frequently observed. These mutations br<strong>in</strong>g about disregulation of<br />
the oncogenes that are known to be a significant <strong>in</strong>itiat<strong>in</strong>g event <strong>in</strong> the pathogenesis of<br />
MM. The consequence all of these mutations is proliferation of a plasma cell clone and<br />
genomic <strong>in</strong>stability that leads to further mutations, deletions and translocations.<br />
Table 1.2. Prevalance of Important Translocations <strong>in</strong> MM (Adapted from Sawyer et al.,<br />
1998; Kuehl and Bergsagel, 2002; Avet-Loiseau et al.,2002).<br />
Translocations Prevalance<br />
11q13 (cycl<strong>in</strong> D1) 15%<br />
4p16 (FGFR3 & MMSET) 15%<br />
6p21 (cycl<strong>in</strong> D3) 3%<br />
16q23 (c-maf) 4%<br />
20q11 (mafB) 2%<br />
8q24 (mafA) 1%<br />
TOTAL 40%<br />
Translocations between t(4;14) (p16;q32) or t(14;16) (q32;q23), partial (q14) or<br />
complete loss of chromosome 13 and partial loss of 17p13 refer to high risk of MM<br />
(Stewart and Fonseca, 2005; Tassone et al., 2006). In addition to these data,<br />
translocation t(11;14) (q13;q32) that is activated Bcl-1 oncogene is the most common<br />
chromosomal difference (Stewart, 2008). This translocation is also seen <strong>in</strong> other<br />
hematological cancers. Besides, <strong>changes</strong> <strong>in</strong> the number of chrosomes are frequently<br />
encountered <strong>in</strong> MM, especially hyperdiploidy is seen at the 3., 5., 7., 9., 11., 15., 19.<br />
and 21. chromosomes whereas hypodiploidy is seen at the 8., 13. and X chromosomes<br />
(Gahrton and Durie, 1996; Mah<strong>in</strong>dra et al., 2010).<br />
In MM, the chromosome 14 abnormality is observed nearly 50% of all cases of<br />
<strong>myeloma</strong> and aberration of chromosome 13 is also observed <strong>in</strong> about 50% of cases with<br />
85% monosomy 13, while the rema<strong>in</strong><strong>in</strong>g 15% constitute deletion of chromosome 13<br />
(Munshi and Avet-Loiseau, 2011; Sawyer, 2011).<br />
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