Hi Everyone,
We've had a number of new members join recently so I thought now
might be a good time to post a review of the CML jargon we often
use. For those who might be getting lost in the alphabet soup, I've
copied and pasted the Glossary we have in the files section that
Richard did for us a few years ago. I've shortened it here to
include just the more common terms we use. If anyone wants to see
the longer version, you can access it in the files section on the
left of the screen.
Please don't hesitate to ask any questions.
Take care,
Tracey
dx Jan 2002
ABL = a gene (named for a researcher whose last name was Abelson) on
human chromosome # 9, involved in normal white blood cell
replication. Abl only causes trouble when it leaves to join
chromosome #22, creating the bcr-abl gene. (See bcr-abl)
Absolute neutrophil count = the total number of neutrophil cells per
microliter of blood. It is calculated by using the total white blood
count (WBC) and the percentage of neutrophils shown on the
laboratory "differential."
ALT = alanine aminotransferase: a blood test used to detect liver
inflammation (see AST)
ANC = absolute neutrophil count
ASH = American Society of Hematologists
AST = aspartate aminotransferase: a blood test used to detect liver
inflammation (see ALT).
Basophil = a type of myeloid white blood cell which is often elevated
in CML
Bcr = breakpoint cluster region a gene on human chromosome # 22
which is involved in the pathophysiology (abnormal functioning) of
CML
bcr-abl = the abnormal gene that characterizes the leukemic stem
cells of most people with CML. For CML to occur, the "abl" gene
(named after a researcher named Abelson) must come unglued from its
usual location on chromosome # 9, and become attached to the "bcr"
(breakpoint cluster region) of chromosome #22, thus creating the bcr-
abl hybrid, or "chimera" which has a number of nasty properties. It
appears that the genetic "mistake" producing bcr-abl is quite common
and may occur several times during the lives of normal people;
however, their immune systems recognize and kill the abnormal cells.
This fails to happen in people who develop CML, but it's not known
why.
BMA = bone marrow aspiration--a procedure in which liquid contents of
a patient's bone marrow are withdrawn (aspirated) through a needle.
This procedure is used to make the diagnosis and to follow the
progress of treatment of CML.
BMB = bone marrow biopsy--similar to a bone marrow aspiration, but
used less frequently and performed with slightly different
equipment. It is used when a larger or different kind of sample of
marrow is needed, or when a BMA is unsuccessful because the marrow is
too fibrous to permit aspiration through the BMA needle.
BMT = bone marrow transplant
Bone marrow = the central portion of our bones, where the majority of
blood cells types are made and stored. Bone marrow contains many
other types of tissue besides blood cells, including a fine meshwork
of bone ("spicules"), connective tissue, and blood vessels.
Bone marrow transplant (BMT) = a procedure in which bone marrow is
taken from one person and given to another, for therapeutic
purposes. In fact, this procedure is rarely used nowadays, having
been largely replaced by stem cell transplants (SCT's); however, many
people still use the term BMT even when they're referring to an SCT.
BUN = Blood Urea Nitrogen (a measure of kidney function)
CBC = complete blood count-- a blood test that measures the
proportions and total number of white blood cells, red blood cells,
and platelets. It also gives information concerning the shape, size
and variation of these cells. In CML a "white cell differential" is
usually performed along with the CBC. This tells which of several
kinds of white cells are present, and in what proportion.
CCR = complete cytogenetic response--absence of leukemic (Ph+) cells
in the bone marrow by either conventional or FISH cytogenetic testing.
CHF = Congestive heart failure
Chromosome - in a cell nucleus, a structure containing a molecule of
DNA that transmits genetic information . Each organism of a species
normally has a characteristic number of chromosomes in its somatic
cells; the normal number for humans is 46. The chromosomal mutation
leading to CML involves chromosomes number 9 and 22 - though if the
disease is untreated, other chromosomal abnormalities accumulate as
well. This process is called clonal evolution.
Chronic myelogenous leukemia (CML) = a disease involving the
overproduction of certain types of white ("myeloid") blood cells.
Untreated, CML progresses through three phases chronic;
accelerated; and acute, or blastic phase each of which is shorter
and harder to treat than the last. Also called chronic "myeloid"
or "myleocytic," or "granulocytic" leukemia
Clonal evolution = the accumulation of DNA (chromosome) mutation
which occurs in untreated CML, and which leads to progression of the
disease.
Cytogenetics. Cyto = cell; genetics refers to looking at the cells
chromosomes, their genetic material. Two types of
cytogenetics, "conventional" and FISH, are used to diagnose and
follow the course of CML. Conventional cytogenetics (so called
because it's been around a long time) is a microscopic exam of up to
25 marrow cells in a phase of cell division when their chromosomes
can be clearly seen and differentiated.
Cytogenetic response (CR) is a response to treatment of CML that
occurs in the marrow, rather than just in the blood..... There are 3
levels of cytogenetic response: 1) just plain cytogenetic response
(CR); 2) Major cytogenetic response (MCR); and 3) complete
cytogenetic response (CCR). A plain cytogenetic response means any
Ph+ less than you began with; major means 35% or less, but more than
0%; and complete cytogenetic response means 0% Ph+ cells as measured
by either conventional or FISH cytogenetic testing (though the PCR
test may still be positive).
DNA = Molecule that carries genetic information. The DNA is
assembled into discrete packets called chromosomes. Humans have 23
pairs of chromosomes, or 46 of them, total, in each cell.
Donor Leukocyte Infusion (DLI) - a procedure done for relapsed
SCTs. Immune system cells are taken from the original donor and
transfused to the CML patient.
Dx = abbreviation for "diagnosis"
Enzyme = a protein that catalyzes changes in other biological
substances. Too many white cells are produced in CML because of an
abnormal tyrosine kinase enzyme - whose sole activity is sticking
phospate molecules onto tyrosine molecules. It's hard to imagine
that so much mischief could be caused by such a simple act!
Fluorescence In Situ Hybridization (FISH) - a cytogenetic test that
is used to reveal the presence of the "bcr-abl" gene. The abl DNA
shows up as a red dot in the microscope slide and bcr DNA shows as a
green dot (see http://path.upmc.edu/cases/case171/mole.html for a
nice picture). In the nuclei of normal cells, where abl and bcr are
on different chromosomes, these dots appear separately. But in Ph+
leukemic cells where bcr and abl are fused, the dots appear
together. If you see RedGreen the cell is Ph+, while Red-------Green
(that is, they're far apart) is Ph-, normal. Clever, huh?
G-CSF = granulocyte colony stimulating factor (brand name Neupogen) =
a naturally occurring hormone that stimulates white blood cell
production
Graft vs. host disease (GVHD) = a collection of ailments that
complicate stem cell (bone marrow) transplantation. In GVHD, the
donor's immune system (the "graft") attacks various of the patient's
(the host's) tissues.
Hematologic response = normalization of the white blood cell counts
in the blood, though not necessarily in the bone marrow. The response
can be partial (reduction in white cells, but not down to normal
range) or complete (white blood count at or below approximately
12,000 white cells/microliter)
Hydrea (hydroxyurea, HU) = a chemotherapy drug which is often used
first in the treatment of CML. Lethal to mature leukemic cells
Hydrea can bring elevated white blood counts (WBCs) back to normal;
however, it does not kill many leukemic stem cells in the bone
marrow, and therefore does not effectively slow the progression of
the disease.
IFN = interferon
IM imatinib mesylate, the brand name for Gleevec (Glivec, outside
the US and Canada)
LAP = leukocyte alkaline phosphatase: a chemical produced in high
quantities in certain leukemias, but always low in chronic phase CML.
A low serum LAP is thus used to support the diagnosis of CML.
LD (or LDH) = Lactate dehydrogenase = an enzyme produced by certain
cell and tissue types. It is used to help diagnose CML "blast"
phase, since blasts produce LDH in abnormally high quantities.
Leukemia = cancer of the white blood cells. Leukemia literally
means "white blood" (leukos = white, and emia.)
Leukocyte = white blood cell (leukos = white; cytos = cell in
Greek). The main types of leukocytes are neutrophils, lymphocytes,
monocytes, basophils, and eosinophils.
LLS = Leukemia & Lymphoma Society
Lymphocyte = a type of white blood cell generally not involved in
CML. Two main types of lymphocytes are B-Cells and T-Cells.
Mini-transplant = non-myeloablative stem cell transplant (mini-
transplant) - a type of stem cell transplant in which the patient's
marrow (myelo-) is not destroyed (ablated) prior to the transplant
procedure
Minimal residual disease = a term used where bcr-abl is still
detectable by PCR, but cytogenetics are negative, or nearly so.
Molecular response (aka PCRU) = defined as a negative PCR or other
negative molecular test.
Myelofibrosis = replacement of blood stem cells in the bone marrow
with fibrous tissue. Myelofibrosis occurs as a complication of CML
and of its treatments, especially interferon.
Myeloproliferative disorder (MPD) = a family of diseases involving
the overproduction of one or another marrow cell types. CML is a
myeloproliferative disorder.
Neutrophils = the type of myeloid white blood cell which is most
increased in CML. Also referred to as polys (polymorphoneuclear
neutrophils); granulocytes (though this term also includes other
types of white cells, such as basophils and eosinophils); and neuts.
PEG-IFN = pegyllated interferon: interferon (IFN) that has PEG
(PolyEthylene Glycol) molecules attached to it. PEG gives IFN a
longer half-life in the body, and may reduce the drug's toxicity and
increase its effectiveness.
Ph = Philadelphia Chromosome.
Ph+ and Ph- refer to the presence and absence, respectively, of the
Philadelphia chromosome in white blood cells of CML patients. The
proportion of Ph+ to Ph- cells is used to track progress in treating
the disease: anything less than you started with is called a
Cytogenetic Response (CR); 35% or less Ph+ is a Major Cytogenetic
Response (MCR), and 0% Ph+ is a Complete Cytogenetic Response (CCR).
Philadelphia chromosome (Ph) is a term used to describe the abnormal
appearance certain chromosomes (chromosome #22), in dividing white
blood cells found in 95% of people who have CML. The Philadelphia
chromosome results from a mutation that involves the swapping of
genetic material between chromosome # 9 and chromosome #22 (see bcr-
abl)
Phillies = abbreviation for philadephia chromosome positive (Ph+)