IMM2022 Study Guide - Final Guide: Myc, Myeloma Protein, Cell Adhesion Molecule
4 May 2018
School
Department
Course
Professor
Cancer Immunology
*evidence for immune surveillance is on the
exam
Cancer: is a disease of multiple genetic
mutations – the development of cancers from
normal tissue proceeds via a process akin to
Darwinian evolution a success of genetic
changes, each conferring a growth advantage.
In order to become a cancer the cell must
have at least 6 traits HALLMARKS OF
CANCER
1. Self sufficiency in growth signals
Eg. Activate H-RAS oncogene
Normal cells need a mitogenic signal before
they can proliferate eg IL-2. Protooncogene
normal gene that can turn to an oncogene
by dominant gain of function mutation eg
C-myc. Is translocated from chrm 8 to chrm 14
in Burkitts lymphoma.
Burkitts lymphoma
Is a cancer of the lymphocytes and commonly
involves B-cells. Burkitts lymphoma is caused
by a DNA translocation leading to activation of
C-myc driven by the Ig promoter, causing B
cell proliferation to become dysregulated.
Instead of making Ab, the cell makes
molecules that drives cell division B cells
become hyperproliferative leading to
lymphoma. (BL is caused by uncontrolled
expression of molecules associated with cell
division)
2. Insensitivity to anti-growth signals
Eg lose the retinoblastoma gene
Tumour suppressor: loss of function mutation
recessive (2 hits)
eg. P53 – initiates apoptosis
eg. BRCA-1 repairs DNA
3. Evading apoptosis
Eg. Produce IGF survival signals.
Apoptosis occurs by activating BAK/BAX or
inhibiting BCL2 suppressor. In cancer the BCL2
is often over-expressed. Ebg by a mistake in
VDJ recombination translocating the BCL2
from chrm 18 to the heavy chain locus on
chrm 14 gives rise to a slow growing
lymphoma.
4. Acquisition of limitless proliferative
capacity
Eg. Turn on telomerase. Overcome the
senescence of telomerase by dysregulation of
the enzyme telomerase. This stops the
telomeres loosing integrity.
5. Sustained angiogenesis
Secrete pro-antigenic factors regulate own
environment get nutrients and eliminate
wastes.
6. Tissue invasion and metastasis
Eg inactivate E-cadherin (normally used in cell
adhesion)
Metastasis is the ability to migrate to new
sites through changes in adhesion molecules
and proteases.
These changes can occur in immune cells
Leukemia: bone marrow cells, lymphoid OR
myeloid origin
Lymphoma: tumour of non-recirculating
lymphoid cells in the lymph nodes (B or T)
Myeloma: malignancy of plasma cells forming
lesions in the bone marrow. Here the plasma
cells are affected myeloma cells secrete
paraproteins (like monoclonals) bone
destruction and kidney damage.
Note that malignancies in B cells are more
common than in T cells due to increased
recombination eg in class switching.
ACUTE LYMPHOBLASTIC LEUKEMIA
Immature B cells, is aggressive, highly
proliferative circulating myeloblast cells. ALL is
curable in young people and common
symptoms are fever, lethargy and anorexia.
CHRONIC LYMPHOBLASTIC LEUKEMIA
Mature B cells are affected. Small non-
aggressive cells that are slow growing. CLL is
treatable but not curable and more common
