Condensed overview of Cancer
A cancer develops from
genomic damage (mutations) to
cells that lead to abnormal growth and persistence of the cells
The mutations can lead to epigenomic changes
that turn on or off specialized genes that would protect the cell
becoming a cancer or being detected by the immune system.
* Lymphomas are highly sensitive to
standard chemotherapy and radiotherapy, which work by damaging the
DNA of rapidly dividing cells causing the cells to initiate
programmed cell death.
Targeted approaches to treating cancer include:
1) by inhibiting the pathways in the cell that are activated by the
mutations that drive the malignant behavior
2) by activating genes that have been silenced, or by turning off
overactive genes - so called epigenetic treatments
4) by targeting cell surface antigens that are expressed only on
lymphocytes, such as cd20 (Rituxan), cd19, cd22, cd30 ...
5) by inhibiting how the cancer cells corrupt or hijack the host system, such
as the immune system or the blood supply.
Lymphoma is generally
more treatment sensitive than other cancers
Lymphoma arises from infection-fighting
immune cells called lymphocytes. Normal lymphocytes replicate and
increase in number in response to an infection. We feel bad during
infections because of this activity and the inflammation that
arises. When the job is done, the infection knocked out, the
lymphocytes die off so as not to interfere with organ function – and
we start to feel better too.
Lymphoma is similar to a normal reaction to an infection – but a
reaction that does not get turned off. The defective immune cells
continue to persist and divide even when no infection is driving it.
(With some notable exceptions, such as h-pylori positive MALT)
A reason lymphoma is highly sensitive to chemotherapy and
radiotherapy is that the normal cells of this kind have an
inherently short lifespan … they are built for fast replication but
also for fast dying.
Immune cells of this type are inherently chemo- and
radiation-sensitive … as evidence by how our normal lymphocytes
counts nose-dive during chemotherapy – unlike most other types of
cells in our body. Importantly, these important cells emerge again
from stem cells that divide infrequently and are not adversely
affected by standard kinds and doses of chemotherapy or radiation.
Within a few weeks or more, the normal lymphocytes needed to protect
us from infection rebound to normal levels.
In the News:
The Hallmarks of Cancer - click
the Figure tabs to walk through this comprehensive presentation
What is cancer?
What is lymphoma?
How does it start?
What determines its
"Lymphoma is a blood cell cancer. The effected cells are
lymphocytes, a type of white blood cell that helps protect us
Cancer begins with damage
to DNA in the cell nucleus. These "hits"
can result from random errors, or by exposures to chemicals
But the cell has defenses:
It can initiate cell death
(suicide) when a defect is detected (so-called apoptosis),
or it can repair the error and
become a normal cell.
If these defenses fail, an atypical
cell is formed.
But multiple "hits" on the DNA are
required to cause a cancer.
A third line of defense is your immune system.
For example, T-cells or Natural Killer cells can detect abnormal
cells and kill them. Tumor cells may develop ways to shut down
the immune system and avoid attack, such as by immune checkpoint
In normal tissues, the rates of new cell growth and old cell death are kept in balance.
In cancer, this balance is disrupted. This disruption can result from uncontrolled cell growth or loss of a cell's ability to undergo "apoptosis."
Apoptosis, or "cell suicide," is the mechanism by which old or damaged cells normally self-destruct."
are often very sensitive and responsive to different treatments.
Aggressive lymphomas are often cured, and indolent lymphomas
are often managed well when treatment is indicated.
Importantly, recent advances in the understanding of lymphoma
have led to effective new therapies.
World Health Organization Classification of
Simplified - how it begins
Our body is made of countless cells
of many types. Cells have specialized jobs and names, such as skin,
nerve, heart, lung, blood, immune cells, and so on. For the human body to function normally, each organ must have a certain number of cells.
By design, the cells in most organs have a short
lifespan. Therefore, to continue functioning the body needs to replace these lost cells by the process of cell division.
Cell division and cell death are controlled by genes that are located in the cell nucleus.
Genes function like
an instruction manual telling the cell what proteins to make. These
proteins in turn control the behavior of the cell.
Some proteins direct the cell to divide; others how long it will live;
and others begin cell death - a normal process by which the body rids
itself of old, unneeded, or damaged cells.
Under normal conditions there is a balance
in which new cells replace old, and each cell carries out tasks
specific to its kind: Heart cells pump, stomach cells produce
acids, immune cells recognize invaders and kill them, and so on.
The balance ensures that the organs and systems function properly and
serve the needs of the body.
The beginning of cancer
In any cell the genetic code can get damaged so
that the instructions in the "manual" are altered in ways that
produce abnormal types and amounts of proteins that can lead to abnormal behavior of the
... Instead of resting, the cells may continue
dividing; instead of dying the cells stay alive. Mutations may
also turn off genes that can repair damaged DNA, or that can induce
cell death when mutations in the cell are detected. See also tumor suppressor
Lymphocytes are very active cells, which undergo
many normal transformations in their life cycle and many more cell divisions than most other cell types.
They are designed to divide rapidly to address infections, but also
to die off fast when the infection is under control.
Cell division, being a highly complex process, is prone to mistakes. Mistakes may not be "picked up" or may often be inconsequential.
The defective or atypical cell will not necessarily lead to a cancer, however ... additional errors
must occur. Before it becomes a cancer the parent cell divides
many times, passing on the defects
that have malignant potential to the children cells. Additional "hits" on the atypical cells may result from chemical
exposures, viral infections, oxidation, random errors ...
example: An atypical (slightly defective) lymphocyte may be kept active longer
because of chronic stimulation by a bug or virus (chronic infection being associated with higher risk of
- making additional random copy errors more likely to occur.
... The first cell to lose normal growth
control is called the cell
of origin. When the cell of origin divides,
the new cells inherit the genetic defects of the parent cell. Thus,
in cancer, the
descendants of the cell of origin are clones
of this cell.
A hallmark of cancer cells is that they have growth
and survival advantages over normal cells. Their cell division is not
balanced by cell death. The abnormal cells may eventually form lumps called tumors.
The word tumor simply means a mass of cells. Tumors can be either
benign or malignant. Benign
tumors are not a threat to life or long-term health, while malignant
tumors are. The word malignant means 'showing great malevolence and being disposed to do evil.'
One way that pathologists identify a tumor as being malignant is if
the cells within it are clonal -
all identical to the cell of origin. In contrast, benign tumors are
made up of related but different cells.
The hallmarks of cancer
Limitless potential to divide and grow
Resisting cell death (resisting apoptosis - normal
programmed cell death)
Evasion of detection by the immune
Inhibition of immune action (immune
Development of a sustaining blood supply
Self sufficiency in growth signals
Insensitive to anti-growth signals
Tissue invasion and metastasis (spreading beyond
the organ of origin)
Reprogramming of energy metabolism
Recruitment of normal cells that contribute to the acquisition
of hallmark traits by creating the "tumor microenvironment."*
Note: Lymphomas are
considered systemic cancers, because both normal and abnormal lymphocytes
(the cell of origin) have the capacity to migrate anywhere in the
body to fight infection. Thus, finding lymphoma cells in the
bone marrow or spleen is not unusual, and not considered a metastasis.
Hallmarks of cancer: the next generation.
This report has added emerging hallmarks:
1) reprogramming of
energy metabolism and
2) evading immune destruction.
Lymphoma is a kind of blood cancer
Blood is a fluid made up of plasma and many types of
blood cells, such as red blood cells (erythrocytes), white blood cells
(leukocytes) and platelets.
Blood circulates through the heart, arteries and veins. It carries
"nourishment, hormones, vitamins, antibodies, heat and oxygen to the body's tissues."
B-cell Cancers by Cell Maturation Stage -
Click to enlarge
Lymphoma is a cancer that affects a type of white blood cells called lymphocytes – immune cells that normally protect you from illness. About
85% of lymphomas are of b-cell origin, and 15% of t-cell
originate and mature (differentiate) in the bone marrow.
T-cells also start out in the bone marrow, but they
differentiate and mature in the thymus gland.
Killer cells are a third kind of lymphocyte. They
specialize in killing foreign cells and possibly signaling to alert
other immune cells of invaders.
Click to enlarge
The different types of lymphoma are determined according to what type of lymphocyte has become
cancerous, and the stage of development. Click b-cell cancers by cell development
to enlarge the illustration shown above.
As with other cancers, the root cause of lymphomas is
damage to genes that leads to abnormal growth controls in the cell.
Lymphomas are a Family of Related Cancers.
The cell of origin determines the subtype of
lymphoma, and influences its clinical behavior - growth
rate and sensitivity to treatments.
The cell of origin,
such as T-cell, B-cell, and NK cell, and the stage of maturation
of that cell determines the type of lymphoma. This is often referred to as the cell
type or diagnosis,
such as follicular small cleaved lymphoma.
When a lymphocyte becomes malignant, its
biologic behavior is arrested at that stage. This stage of development
influencing its location tendencies
and growth rate and other cellular
Analogy: Consider that just as
children grow faster than adults, cells at earlier stages of
development tend to grow faster than they do at mature stages.
The malignant cells then may accumulate to form tumors that enlarge the
lymph nodes or spread to other areas of the lymphatic system, such as the spleen or bone marrow, or outside the
lymphatic system to the skin, or mucosal linings of the stomach.
How widespread the lymphoma is, is summarized by
Staging is the process of determining where the lymphoma is located by imaging
and other methods.
NOTE: It's common for the lymphoma to be at stage IV at diagnosis. But, advanced stage of disease
does not mean the treatments will not be effective.
About growth rate. The
cell of origin will also influence
how fast or slow the lymphoma cells will
tend to grow. The growth tendency of the lymphoma is also called
Aggressive grade lymphomas
and grow rapidly, and therefore prompt and aggressive treatment is
Indolent grade lymphomas
may not divide faster than normal lymphocytes. Here the malignant
behavior can be resistance to cell death - a
failure to "erase" itself after it's normal functions have
been completed. This results in a slow buildup of excess
cancer cells causing tumors to form, but more
Mutations also influence the clinical behavior
The specific damage to DNA - and the gene expression
- is likely to be variable
for patients who have the same diagnosis.
These differences may explain,
in part, why
patients with the same diagnosis can have lymphomas that develop at
different rates, and respond differently to the same treatments.
Recall that genes expression determine what proteins the cells express
and this determines behavior. Response to treatment
is also cell behavior. For example, cells detecting damage to
DNA - induced by treatment - will initiate cell death, but only if the
genes that can activate the cell-death program are functioning or
activated by the treatment.
"Ultimately, it may well
be that the optimal treatment will be determined by patient clinical and biological characteristics." ~ Dr. Bruce Cheson - Advances in the Treatment of
Non-Hodgkin's Lymphoma - Medscape
Your Lymphoma is Unique
Factors that may account for clinical differences in
The cell type:
T-cell, B-cell, NK-cell, and subtypes of each;
The stage of
development of the cell of origin;
Slight differences in
stage of development;
Specific damage to the
Different patterns of
gene expression - silent versus active genes;
Differences in the
health, strength and characteristics of the immune systems;
Differences in the
microenvironment in the tumors, which are made up of malignant and normal
cells. Here the interactions
among the cells in the tumor may be promoting or stabilizing;
See also Immune
signatures in follicular Lymphoma
The presence or absence
stimulation inside the body. An antigen is defined as a molecule that
is recognized by the immune system as something that does not
belong in the body.
Activation of lymphoma
cells, like normal lymphocytes, may be promoted by an antigen,
such as a bacteria, virus, ... or normal molecules the immune
system mistakes to be foreign (as in an autoimmune response).
For example, a bacteria (the antigen) may trigger the cancerous lymphocyte to activate and
divide, thus promoting the growth of the lymphocyte tumors. MALT
is a subtype of lymphoma that
develops in the mucosal linings. This lymphoma can resolve in many
cases by treating a
bacterial infection called H-pylori.
Quote: "As we move to consider these tumors by their genetic
abnormality (genotype) rather than their cellular
appearance (phenotype), one converts the generalities of
leukemia, lymphoma, and myeloma into hundreds of diseases
with distinct genetic causes, clinical manifestations, and
drug responsiveness." Source
Encouraging Developments: New technologies,
particularly microarrays, can help to characterize gene expression in
malignant cells, allowing scientists to see what is wrong, and compare
one person's cancer to another's. For the first time in history we can
begin to see what we are trying to fix at a fundamental level,
and this is likely to lead to rationale selection of cancer therapies,
as well as faster drug development and testing. See NBN
for more details.
Understanding cancer series nci.nih.gov
An exceptional educational series provided by the National Cancer Institute: