changes in protein profiles in bortezomib applied multiple myeloma ...

A rare form of MM called Nonsecretory Myeloma occurs in about 1% of
myeloma patients. In this disease, neoplastic plasma cells do not produce any
immunoglobulin chains, heavy or light (Shaw, 2006).
1.2.2. Molecular Pathways of MM
MM is a plasma cell malignancy characterized by very complex cytogenetic and
molecular genetic aberrations.
Cancers can be caused by mistakes, defects or certain changes in the DNA
called mutations that turn on oncogenes or turn off tumor suppressor genes. DNA is a
complex molecule and the fundamental building block for a human's entire genetic
makeup. It is a component of virtually every cell in the body. Certain genes that are the
parts of the DNA and responsible for promoting cell division are called oncogenes and
others that take charge in slowing down cell division or causing cells to die at the
appropriate time are known tumor suppressor genes.
Chromosomal translocations and/or point mutations, amplifications of proto-
oncogenes and inactivations of tumor supressor genes are the important mechanisms
that cause to progression of MM. Oncogenes which are active in this disease and their
activation mechanisms are shown in the Table 1.1 (Gahrton and Durie, 1996).
Oncogenes Chrosomal
Locations
Table 1.1 Genetic Alterations in MM
Activation
Mechanism
c-myc 8q24 Trasnlocation
Literatures
(Greil et al., 1991),
(Cobbold et al., 2010)
bcl-2 18q21 Trasnlocation (Pettersson et al., 1992)
N-ras 1p11-13 Point Mutation (Portier et al., 1992)
K-ras 12p11-12 Point Mutation (Portier et al., 1992)
p53 17p13 Point Mutation
Deletion
(Neri et al., 1993),
(Portier et al., 1992)
Rb1 13q14 Deletion (Gahrton and Durie, 1996).
c-MAF
14q16 or
14q20
Trasnlocation
(Sawyer et al., 1998) (Kuehl
and Bergsagel, 2002)
8