Among acute leukaemias, Acute Promyelocytic Leukaemia (APL) was first recognized as a distinct disease entity in 1957. Acute Promyelocytic Leukaemia (APL) is classified as the M3 variant of Acute Myeloid Leukaemia (AML) in the internationally accepted French-American-British (FAB) Classification and accounts for 5-10% of cases of AML1 .
APL deserves special attention, for its characteristic chromosomal abnormality, a translocation (or cross link exchange of chromosome material) between chromosome 15 and 17. This joins two normally separated genes, the promyelocytic (PML) gene on chromosome 15 and the retinoic acid receptor-α (RAR-α) gene on chromosome 17. The new fused PML/RAR-α gene starts producing an abnormal protein which has proven to inhibit the differentiation of the myeloid precursor cells into more mature cells and lead to an abnormal malignant cell. Therefore this translocation written t(15;17) is not only a mere marker or the hallmark of APL, but is the cause of APL.
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) which can induce a complete remission in patients with APL by causing the APL-malignant cells (blasts) to mature.
APL Signs and Symptoms
The early symptoms of APL are nonspecific and include, for example, fatigue (feeling tired), minor infections, or a tendency to bleed (haemorrhagic diathesis). All signs and symptoms are directly linked to the usual blood cell defected called pancytopenia. Pancytopenia is a dramatic decrease in the 3 main blood cell lines, including the red blood cells (that carry oxygen to tissues, this is link to fatigue), white blood cells or granulocytes (that fight infections) and platelets (that are needed for blood to clot normally).
Furthermore, in APL there is a pronounced tendency for bleeding due not only to low platelet count, but also to several associated coagulation disorders. These disorders are close to disseminated intravascular coagulation (DIC). The bleeding tendency can manifest itself as petechiae (little bleeding spots in the skin or elsewhere), small ecchymoses (bruises), epistaxis (nose bleeds), bleeding in the mouth, haematuria (blood in the urine), and women, who are menstruating, may have excessive irregular menstrual bleeding.
Some molecular variants are also generally believed to be associated with a poorer prognosis or resistance to treatment with all-trans retinoic acid (ATRA). One such variant, characterized by a different translocation t(11;17), represents about 0.8% of APL.4 The presence of mutations called FLT 3 is also associated with a significant lower overall survival.5
Dr. Anne Bancillon
MSL European Director
Medical Affairs
Cephalon Europe
References
1 Bob Löwenberg, James D. Griffin and Martin S. Tallman Acute Myeloid Leukemia and Acute Promyelocytic Leukemia , Hamatology 2003, American Society of Hematology, pp 82-101
2 Http://www.medterms.com/script/main/art.asp?articlekey=19757 – last accessed on October 25, 2006
3 Lo Coco F, Diverio D, Falini B, et al. Genetic diagnosis and molecular monitoring in the management of acute promyelocytic leukemia. Blood. 1999;94:12–22
4 Licht JD, Chomienne C, Goy A, et al.: Clinical and molecular characterization of a rare syndrome of acute promyelocytic leukemia associated with translocation (11;17). Blood 85 (4): 1083-94, 1995
5 Kuchenbauer F and coll: Impact of FLT3 mutations and promyelocytic leukaemia-breakpoint on clinical characteristics and prognosis in acute promyelocytic leukaemia.Br J Haematol 2005 Jul;130(2):196-202.