Leukemia is a malignant neoplasm of hematopoietic
tissue originating in and infiltrating the bone
Leukemia generally involves the peripheral blood, and
often infiltrates the spleen, liver, and lymph nodes.
Leukemia is classified into the major categories of acute
and chronic leukemia.
Acute leukemia is characterized
byproliferation of immature cells or blasts.
If untreated, death usually occurs within 6 months
in most patients.
Chronic leukemia is a proliferation of
mature appearing cells, again in the marrow,
peripheral blood, and various organs. The clinical
course is relatively indolent, compared with acute
leukemia, and ranges from 2-6 years depending on
the subtype of the proliferating cell.
A few common chromosomal
M3 - rx retinoic acid
inv, del, t(16q)
M5 (particularly M5a); M4
t(9;22) - Philadelphia chromosome
t(8;14), t(2;8), t(8;22)
** Most common type of AML
The acute and chronic leukemias are further classified
according to their cell lineage into two major
categories: myeloid and lymphoid.
Thus there are acute leukemias, either acute myeloblastic
leukemia (AML) or acute lymphoblastic leukemia (ALL) and
there are chronic leukemias, either chronic myelocytic
leukemia (CML) or chronic lymphocytic leukemia (CLL).
The acute leukemias are classified using the FAB*
Classification (1975;1985 revision).
While classification of the acute leukemias is fairly
straight forward, the classification of chronic bone
marrow neoplasms is less clear. A classification scheme
based on our current knowledge, is presented on the next
*French, American, British Classification
Neoplastic clonal proliferations of pluripotent and
multipotent myeloid stem cells result in one of the
chronic myeloproliferative disorders: chronic
myelocytic leukemia (CML), polycythemia vera (PV),
myelofibrosis (MF), or essential thrombocytosis (ET).
The chronic lymphoproliferative disorders or
leukemias are a diverse group, being of T, B, and
natural killer (NK) origin and having variable
Leukemia: Introduction -
Approximately 10% of all malignant neoplasms are
leukemias for about 27,800 new cases/year and 18,100
deaths/year (1990). The incidence rate is almost 10 new
cases /100,000 people in the US. The number of new cases is
split evenly between acute and chronic leukemia.
Of the 27,800 new cases, 2,500 are in children (<15
years). Leukemia occurring in children is almost always
acute with a 4:1 ratio of lymphoid to myeloid leukemia. This
is the reverse of that seen in adult leukemia.
The incidence of acute myeloblastic leukemia (AML) rises
with increasing age and is the most common (80-90%) adult
leukemia and 45% of all leukemias.
Acute lymphoblastic leukemia (ALL) peaks at age 4,10% of
Chronic lymphocytic leukemia (CLL) also increases in
incidence with rising age, but is rare before the age of 40
and almost never seen in childhood,30% of all leukemias.
Chronic myelocytic leukemia (CML) peaks at age 30-50, but
can occur at any age, 15% of all leukemias.
Leukemia: Introduction -
The incidence of ALL is almost twice (1.8:1) as high in
white as in nonwhite children. There is no apparent
predilection for race or sex among the myeloid
In the 1st 10 years of life siblings of patients with
leukemia have a 4-fold increased risk of leukemia with
identical twins having a 20% chance of developing
There is approximately a 20 fold increase incidence of
leukemia in children with Down's syndrome.
Other disorders (autosomal recessive) associated with
leukemia include Bloom's syndrome, Fanconi's anemia, and
ataxia telangiectasia (all disorders with defective DNA
excision &/or repair).
Immunodeficiency diseases (ataxia telangiectasia;
agammaglobulinemia) may also be associated with
Etiology is unknown in most cases of leukemia.
There are several animal models for a posssible viral
etiology involving retroviruses with oncogene (e.g.
Avian Erythroblastosis virus) and without oncogene (e.g.
Avian Leukosis virus) involvement. In humans there is strong
evidence of a viral etiology for Adult T cell
Leukemia/lymphoma associated with HTLV-I (geographically
isolated to SW Japan, the Caribbean, and some sections of
Africa). African Burkitt's lymphoma/leukemia is associated
with the Epstein-Barr virus.
Environmental factors such as irradiation (e.g.
increased incidence of leukemia in survivors of the atomic
bomb explosions in Japan); early radiologists (9 fold
increased risk); patients who have received therapeutic
irradiation), chemical toxins (e.g. benzene, ), and
drugs (e.g. chloramphenical, phenylbutazone, and
especially alkalating agent chemotherapy) have been
associated with leukemia.
Leukemia: Introduction -
From a morphologic and kinetic stand-point, there is a
failure to differentiate and mature into functional
hematopoietic cells. There is a loss of feed-back
control, resulting in an over proliferation of immature and
often functionally abnormal hematopoietic cells. Such cells
may lack certain surface/cytoplasmic proteins and enzymes,
ie. myeloperoxidase deficient, or produce aberant products,
ie. hemoglobin F. It is likely that leukemic cells produce
cytokines or growth factors that inhibit normal
In most instances the leukemic cells remain
functionally immature. Thus while retaining the
capability to proliferate, they remain, for the
most part, in the marrow space, replacing normal
The doubling time of leukemic cells can be as
short as 4 days because of an espicially large growth
fraction. Otherwise these cells divide more slowly than
normal cells (an S-phase almost 3 times normal) and have a
high rate of cell death
In acute leukemia doubling times may be on the order of 4
days, a newly transformed neoplastic cell can undergo 30
doublings to yield
10 cells (the limit of current standard detection) and 10
additional doublings to get to 10 cells (displacement of
normal marrow elements). Thus it might take 40 days or less
to evolve from the initial event to fully symptomatic
Doubling times are much lower in CLL which has a paucity
of cells in division.
Ineffective hematopoiesis and chemotherapy result in cell
death and turnover of nucleic acids, increasing uric
acid levels and causing hyperkalemia.
Metabolically active leukemic blasts consume large
amounts of oxygen.
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