A woman in her 20s presented with menorrhagia, bleeding gums, and frank hematurea. Her hemoglobulin was 9.2 g/ dL and white cell count was 3.1 3 10 9 /L, with neutrophils amounting to 0.6 3 10 9 /L. Her platelets measured 12 3 10 9 /L. She also had deranged clotting with prolonged prothrombin time, normal activated partial thromboplastin time, and low fibrinogen. The blood film showed abnormal promyelocytes. The bone marrow aspirate showed shift to left in granulocytic cells with maturation arrest at promyelocyte stage. There were excess blasts (18%) and abnormal hypergranular promyelocytes (67%). Faggot cells-blasts and promyelocytes with multiple Auer rods-were also seen (a-h; Giemsa 10003). Flow cytometric analysis showed an abnormal population of cells expressing CD13, CD33, myeloperoxidase, and CD38, along with weak expression of CD11b, CD10, CD117, and CD2. These cells did not express CD34, HLA-DR, CD15, CD16, or any B lineage markers. The immunophenotypic and the morphological features on peripheral blood and bone marrow aspirate were most typical of acute promyelocytic leukemia (APL). Bone marrow trephine biopsy showed hypercellular marrow with a cellularity of nearly 100%. The myeloid:erythroid ratio was >10:1 (i; H&E 1003). Marrow showed sheets of abnormal promyelocytes with abundant granular cytoplasm (j; H&E 6003). These abnormal cells expressed myeloperoxidase (k; 6003), CD99, CD43, CD68 (l; 6003), and CD117 (weak) (m; 6003) and were negative for CD34 (n; 6003), HLA-DR (o; 6003), CD68R, and CD10. Megacaryocytes were rare. Marrow reticulin was minimally increased (Grade 1). The trephine features were characteristic of APL. Karyotypic analysis showed reciprocal translocation between the long arms of chromosomes 15 and 17 in four of ten metaphases (p). Interphase FISH analysis on cultured bone marrow cells using a probe for PML/RARA (Kreatech Diagnostics) revealed a fusion signal, consistent with a PML-RARA [t(15;17)] fusion gene, in 94 of the 100 cells analyzed (q). This finding is consistent with a diagnosis of APL.
Acute promyelocytic leukemia (APL) compromises 5-8% of acute myeloid leukemias and is characterized by its distinct morphological, immunophenotypic, cytogenetic, and clinical features. The balanced chromosomal translocation