CML Glossary

[Guest guest]

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

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a patient's bone marrow are withdrawn (aspirated) through a needle.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+)

cells, coined by members of the CML list.

Polymerase Chain Reaction (PCR) test = a very sensitive test which

can be used to detect the presence of very low levels of specific

genetic material (DNA). It is used to detect, and sometimes to

quantify, bcr-abl in bone marrow cells of patients with CML. The

most sensitive PCR tests can detect as few as on in 100,000,000

cells. For an explanation of how PCR works, see

http://www.scientific.org/tutorials/articles/riley/riley.html

Procrit = a brand name for artifically produced erythropoietin, a

hormone that stimulates red blood cell production.

Stem Cell Transplant (SCT; previously known as bone marrow transplant

or BMT - these terms and abbreviations are used interchangeably, but

SCT is technically more correct) = a procedure in which the patient's

marrow cells are replaced with a donor's marrow cells in hopes of

curing a disease.

Translocation = where a bit of genetic material from one chromosome

(humans have a total of 46 chromosomes) is swapped with a bit from

another chromosome. In CML, a piece (called " abl " ) from chromosome #

9 is swapped onto a segment (called " bcr " ) on chromosome #22 to

create the " bcr-abl oncogene " that causes this disease.

Tyrosine Kinase = an enzymes involved in many kinds of communication

within cells. The bcr-abl gene codes for an abnormal tyrosine kinase

that causes much of the mischief in CML.

WBC = white blood count – the number of white blood cells in a sample

of blood.

Zero Club = a term coined by members of the CML list-serve (Zavie

, actually) to refer to patients who have achieved 0% PH+