Let us look at tumors
of the immune system.
Leukemia develops in the bone marrow.
There are a number of
different types of leukemia.
The main ones are acute lymphoblastic leukemia, acute myeloid
leukemia, chronic lymphocytic leukemia
and chronic myeloid leukemia.
There are subtypes of each
of these types of leukemia.
Lymphomas in contrast develop
in the lymphatic system.
Two main lymphomas are Hodgkin
lymphoma and Non-Hodgkin lymphoma.
Myelomas are tumors of plasma cells.
Here we have a stem cell that is
giving rise to pre-B lymphocytes.
Acute lymphoblastic leukemia is usually
derived from immature pre-B cells.
Blasts are present in the
bone marrow and blood.
In chronic lymphocytic leukemia and lymphoma,
the malignant population is mature B-cells.
In CLL, malignant cells
are present in the blood.
In lymphoma, the malignant cells are present in
the lymph node and sometimes in other tissues.
Plasma cells give rise to myeloma.
In myeloma, the clone of malignant plasma cells
produces a monoclonal immunoglobulin; in other words,
all the antibody is absolutely identical because
it’s derived from a malignant clone of plasma cell.
T-cell malignancies are
somewhat less common.
T-cells are not infected by Epstein-Barr virus, which
is a major way in which B-cells can become malignant.
Also T-cells are somewhat more susceptible to
apoptosis, and therefore less able to survive.
There are also myeloid leukemias
derived from myeloid progenitors
as well as these lymphoid leukemias
that you can see on this slide.
Chronic lymphocytic leukemia is rather unusual, in
that the leukemic cells have on their cell surface, a
molecule that is normally present on B-cells, but
also a molecule that is normally present on T-cells.
As you can see in this flow cytometry diagram, there are
normally CD19+ B-cells, and then separately CD5+ B-cells.
However, in chronic lymphocytic leukemia, the cells
express both of those molecules on their surface.
In other words, a molecule that
is characteristic of B-cells, but
also a molecule that is more normally characteristic of T-cells.
Post-transplant lymphoma can arise due to EBV
infection in individuals that are receiving
immunosuppression in order that they do not
reject a transplanted tissue or organ.
Prior to a renal transplant, this woman had
memory T-cells responding to Epstein-Barr virus.
The Epstein-Barr virus infection
was controlled by the T-cells.
However following a transplant, the immunosuppressive drug
cyclosporine has made the memory cells non-responsive.
And there is a polyclonal increase
in EBV infected B-cells.
There becomes a situation in which there is uncontrolled
EBV infection which drives B-cell proliferation.
The polyclonal B-cell proliferation will
improve if the cyclosporine is stopped.
However with ongoing proliferation, Myc
translocation can occur within the B-cells.
There is a malignant transformation resulting from this
Myc translocation, and the development of lymphoma.
The polyclonal growth of B-cells has increased
the risk for this translocation to occur.
The monoclonal B-cell proliferation
will continue after cyclosporine
is stopped, and the patient develops the symptoms of lymphoma.
In multiple myeloma, there are plasma cells
in the bone marrow that become malignant.
And therefore, a clone of rapidly
replicating plasma cells pumping
out huge amounts of antibody of a single specificity develop.
They produce what is
referred to as a paraprotein.
And this can be detected
on a electrophoretic gel.
We can see the paraprotein band in the
gamma region from the patient on this gel.
In contrast, in a healthy individual, that
monoclonal band is missing because their
antibodies are totally polyclonal; a very
huge mixture of different specificities.