A 50 year old female presents with lethargy, bruising and bleeding gums. A full blood count is performed and the following results noted:
Hb 74 g/L WBC 2.3 x 109/L Platelet count 28 x 109/L.
The coagulation results are:
PT 16.9 sec INR 1.3 APTT 27.1 sec.
The blood film is leucoerythroblastic with 48% promyelocytes. Many of the promyelocytes are abnormal with bilobed and reniform shaped nuclei. The cytoplasm is densely packed with large azurophilic granules as well as Auer rods and bundles of Auer rods (faggots).
A provisional diagnosis of acute promyelocytic leukaemia (APL) is made.
Acute promyelocytic leukaemia may occur at any age although it predominantly occurs in adults. There are two types: the hypergranular or ‘typical type’ and the hypogranular or ‘microgranular’ type. Both are characterized by the presence of abnormal promyelocytes in the peripheral blood and bone marrow. The promyelocytes in the hypergranular type have nuclei, which vary greatly in both size and shape. They are often bilobed and reniform or kidney shaped. The cytoplasm is densely packed with large azurophilic granules, which may obscure the nucleus. Auer rods and bundles of Auer rods (faggots) are invariably present. The promyelocytes in the microgranular type have the same characteristic nuclear shape however the cytoplasm shows a paucity or absence of granules. This is due to the submicroscopic size of the azurophilic granules. Auer rods and bundles of Auer rods may also be seen in the cytoplasm.
The bone marrow in APL is hypercellular.
The promyelocytes of APL contain procoagulant material which, when released into the circulation, causes disseminated intravascular coagulation (DIC). Coagulation studies should always be performed when a case of APL is suspected from the blood film.
Flow cytometry performed on APL shows expression of the myeloid markers CD 33 (homogeneous and bright) and CD 13 (heterogeneous). HLA-DR and CD 34 are both negative, demonstrating the presence of a differentiating population of cells.
The myeloperoxidase (MPO) reaction is strongly positive in both the hypergranular and hypogranular type. The reaction product often masks the nucleus as well as the cytoplasm.
Acute promyelocytic leukaemia shows the characteristic t(15;17)(q22;q12). This translocation results from the breakage and reunion of bands 15q22 and 17q12. It is a balanced translocation, which is both specific and diagnostic for acute promyelocytic leukaemia. The standard 15;17 translocation has been analysed in considerable molecular detail. It has been shown that, as a result of this translocation, the truncated retinoic acid receptor alpha gene (RARα) on chromosome17q12 has moved to chromosome 15q22, where it has fused with a gene called PML, giving rise to a new hybrid gene called PML-RARα.
Acute promyelocytic leukaemia stands alone when it comes to treatment. It responds to all-trans-retinoic acid (ATRA) which induces remission by differentiating the leukaemic promyelocytes. This remarkable response to ATRA is directly related to the PML-RARα rearrangement in APL patients.
Treatment with ATRA is combined with cytotoxic chemotherapy.
The World Health Organization (WHO) describes three variant translocations associated with APL. They are t(11;17)(q23;q21), t(5;17)(q32;q12) and t(11;17)(q13;q21).
t(11;17)(q23;q21) is morphologically different from the other variant translocations in that the promyelocytes resemble the shape of normal promyelocytes. The nuclei are round. The cytoplasm is hypergranular and usually lacks Auer rods. There may be increased numbers of pelgeroid forms present. It also does not respond to treatment with ATRA.