Dear Sir, Acute promyelocytic leukemia (APL) is characterized by the translocation of chromosomal (15;17)(q22;q21) involving the fusion of the promyelocytic leukemia (PML) and RARA genes, resulting in a PML/RARA fusion gene on derivative chromosome 15 and reciprocal RARA/PML fusion gene on derivative chromosome 17 [1]. Variant rearrangements have been reported in 5% to 10% of APL patients [2]. We report a case of APL associated with a novel variant translocation. The patient is a 67-year-old male presented with epistaxis. He was found to have pancytopenia and rare abnormally hypergranular, bilobed, immature cells consistent with leukemic promyelocytes on peripheral blood smear. No definite Auer rods were seen. Additional laboratory tests show a prolonged prothrombin time (PT) and elevated D-dimer. Bone marrow aspirate smear showed replacement by the same type of cells noted on the peripheral blood smear. Flow cytometric analysis of the marrow aspirate indicated the presence of a large-sized, immature, hypergranular myeloid population. This population brightly expressed CD33, CD13, CD117, and MPO, dimly expressed CD64, and was negative for CD34, HLA-DR, and CD11b. Cytogenetic G-banded analysis of 20 metaphase cells from bone marrow revealed a karyotype of 46,XY, del (17) (q12q21.1), ins(15;17)(q22;q21.2q25.3)[18]/46,XY[2] (Figs. 1 and 2). FISH analysis using the dual-color, dual-fusion PML (15q22-red)/RARA (17q21-green) probe showed a variant abnormal pattern (Fig. 2). Typical APL patients have 1R (red):1G (green):2F (fusion) signals, indicating the presence of two fusion genes. In our case, this typical abnormal pattern (Fig. 3A) was seen in only 1.5% of the cells. On the other hand, 85% of the cells had 2R:1G:1F (Fig. 3B). PML gene remained on the der (15), and PML/RARA was inserted into or translocated to the der (15) (Fig. 2). This indicated an absence of the RARA/PML fusion gene on the derivative (der) chromosome 17 and the insertion or translocation of the PML/RARA fusion gene to the der (15). The remainder of the nuclei (3.5%) demonstrated a normal signal pattern (2R:2G) (data not shown). Metaphase FISH on ten cells using the TelVysion 17q probe showed that the subtelomeric region of the long arm of chromosome 17 was present on both 17 homologs (data not shown). Reverse transcription polymerase chain reaction performed on the RNA extracted from peripheral blood is positive for PML–RARA transcripts. This case was presented at the 2011 annual meeting of the College of American Pathology in Grapevine (Dallas/Ft. Worth), Texas. M. Bellone : T. Ahmed :Y. Hu Department of Anatomic Pathology, Stony Brook University Medical Center, Stony Brook, NY 11794, USA
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