Definition of Acute promyelocytic leukemia
Acute promyelocytic leukemia definition - medical term Commonly called APL, a malignancy of the
bone marrow in which there is a deficiency of mature blood cells in the myeloid
line of cells and an excess of immature cells called promyelocytes. APL is due to
a translocation (an exchange of chromosome material) between chromosomes 15 and
17 which is symbolized t(15;17). This translocation is not a mere marker of APL.
It is the cause of APL.
APL was first recognized as a distinct disease entity in 1957. It accounts for
5-10% of cases of acute myeloid leukemia (AML). The peak incidence of APL is in
young adults. APL is considered a type of AML and is classified as the M3 variant
of AML in the internationally accepted French-American-British (FAB) Classification.
The signs and symptoms of APL are nonspecific and include fatigue (feeling tired),
minor infections, or a tendency to bleed (hemorrhagic diathesis). There is usually
pancytopenia with low levels of red blood cells (anemia), low levels of the granulocytes
and monocytes (types of white blood cells that fight infections), and low levels
of platelets (that are needed for blood to clot normally). Patients with APL may
therefore receive transfusions.
APL is consistently associated with a disorder that resembles (but is not identical
to) disseminated intravascular coagulation (DIC). There is in APL a pronounced tendency
to hemorrhage (bleeding). The bleeding can manifest itself as petechiae (little
bleeding spots in the skin or elsewhere), small ecchymosis (bruises), epistaxis
(nose bleeds), bleeding in the mouth, hematuria (blood in the urine), bleeding from
venipuncture and bone marrow sites and in girls and women who are menstruating may
have menometrorrhagia (excessive irregular menstrual bleeding). The hemorrhagic
diathesis (bleeding condition) may precede the diagnosis of leukemia by 2-8 weeks.
The t(15;17) translocation in APL is the result of two chromosome breaks: one
in chromosome 15 and the other in chromosome 17. The break in chromosome 15 disrupts
the promyelocytic leukemia (PML) gene which encodes a growth suppressing transcription
factor. And the break in chromosome 17 interrupts the retinoic acid receptor alpha
(RARa) gene which regulates myeloid differentiation. The translocation creates a
PML/RARa fusion gene. It produces a chimeric protein that arrests the maturation
of myeloid cells at the promyelocytic stage. (It reduces terminal cell differentiation.)
And this leads to the increased proliferation of promyelocytes.
The treatment of APL differs from that for all other forms of AML. Most APL patients
are now treated with all-trans-retinoic acid (ATRA). ATRA is a form of "differentiation
therapy." It activates the retinoid receptor RAR and causes the promyeloctes to
differentiate (to mature) and this deters them from proliferating.
ATRA can induce a complete remission in most patients with APL by causing the
APL-blasts to mature. However, ATRA cannot eliminate the leukemic clone. ATRA is
therefore used in combination with chemotherapy including an anthracycline drug.
Survival is better with the combination of ATRA and chemotherapy than chemotherapy
alone in newly diagnosed APL, because ATRA + chemotherapy makes for a slightly higher
rate of complete remissions while allowing significantly fewer relapses. Maintenance
treatment with ATRA, and possibly with low-dose chemotherapy, further reduces the
incidence of relapse.
The prognosis for APL depends on a number of factors including the white blood
cell (WBC) count at the time of diagnosis, etc. Overall, more than 90% of patients
with newly diagnosed APL today can achieve complete remission, and about 75% can
be cured by the combination of ATRA and chemotherapy. In patients who relapse after
remission, treatment may include arsenic trioxide.
The advent of ATRA therapy revolutionized the treatment of APL and markedly improved
the prognosis (the outlook). ATRA syndrome is a serious side effect of ATRA treatment
and includes fever, respiratory distress, and hypotension (abnormally low blood
pressure). The ATRA syndrome can be prevented by the addition of chemotherapy and/or
dexamethasone if the WBC is increasing.
In sum, APL is a form of acute myeloid leukemia caused by a specific chromosome
translocation t(15;17). APL is associated with a characteristic cellular picture
classified as M3 in the FAB Classification and responds favorably to treatments
including retinoids, chemotherapy and, most recently, arsenicals.
Common Misspellings: acute promyelocytic leukaemia, acute promyelocytic lukemeya,
acute promyelocytic lukemia, acute promyelocytic luekemia, acute promyelocytic leukimia
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