Transcript Bun**né základy medicíny D*di*nost

Acute promyelocytic leukemia (APL)
From the worst
to the best prognosis
MUDr. Petr Pavlíček
Internal Hematological Clinics
FNKV and 3LF UK in Prague
APL
• is a subtype of acute myelogenous leukemia
• Acute promyelocytic leukemia is the first
malignant disease highly curable with targeted
therapy directed at a unique molecular
abnormality
• The bleeding (due to coagulopathy) is the most
notorious manifestation of the disease
APL
• Most patients are young, present with
leukopenia, (leukocytosis in 20%)
• Abnormal cells from almost all patients have a
balanced reciprocal translocation between
chromosomes 15 and 17
• Defining abnormality is a translocation of
retinoic acid receptor alpha gene
t(15;17)
t(15;17)
APL
• t(15,17) generates a fusion transcript joining
the PML (promyelocyte) and RAR-α (retinoic
acid receptor-α) genes
Blood cell developement. A blood stem cell goes through several
steps to become a red cell, platelet or white blood cell
APL: Physiologic quantities of retinoic acid no
longer sufficient to allow for cell
differentiation
APL
• The fusion of PML and RARA results in
expression of a fusion protein with altered
functions
• It caused blocking differentiation of
granulocytes
APL
Physiologic level od retinoic acid
with
Pathological receptor (PML/RARa)
Doesn´t work (No differenciation)
APL
• APL is unique among leukemias due to its
sensitivity to all-trans retinoic acid (ATRA)
the acid form of vitamin A
ATRA allows differentiation of the immature
leukemic promyelocytes into mature
granulocytes
Therapeutic level of ATRA overcomes block of
differenciation
APL
• Unlike other chemotherapies, ATRA does not
directly kill the malignant cells
• ATRA induces the terminal differentiation of
the leukemic promyelocytes,
• these differentiated malignant cells undergo
spontaneous apoptosis on their own
APL
• The prognosis of APL was changed, from the
worst among AML as it used to be, to currently
the best.
• a cure rate of approximately 80% to 90% of
patients can be expected
• (all AML 30%)
Case report
• patient (M, 25) visited his GP for headache, flulike feeling, high temperatures over 38°C,
Sorethroat, bleeding from tonsilae
bleeding around incarnated foot-nails on
thumbs
no blood samples taken
ATB treatment was started
and … patient was sent home
Case report
• Treatment without effect, bleeding worsening, with new
localization (gingiva), 4 day later another meeting with GP
• Sent to Hospital
• Blood samples taken next day
• WBC 18,2 G/l
• PLT 16 G/l
• Coagulopathy
• Hematologist consulted, patient sent to hematology
department of faculty hospital
• Diagnose of high-risk APL established
•
• Succesful treatment started…
full recovery
Take Home Message
• Acute promyelocytic leukemia is highly curable malignant
disease
• The bleeding (due to coagulopathy) is the most notorious
manifestation of the disease
• The disease is characterized by a chromosomal
translocation involving Retinoic receptor alpha (RARα) gene
- t(15,17)
• ATRA treatment induces the terminal differentiation of the
leukemic promyelocytes
Thank you!