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A novel t(3;17)(p25;q21) variant translocation of acute promyelocytic leukemia with rearrangement of the RARA locus

Leukemia volume 20, pages 376–379 (2006)Cite this article

The vast majority of patients with acute promyelocytic leukemia (APL, FAB M3) have the t(15;17)(q22;q21) chromosomal translocation (reviewed in Melnick and Licht1). This introduces the gene for PML into the retinoic acid receptor α (RARA) locus, which leads to expression of a PML-RARA fusion. There is convincing evidence that expression of PML-RARA underlies the APL phenotype.1 Yet, there have been rare cases of APL identified that do not manifest t(15;17). Many of these cases exhibit cryptic rearrangements of PML and RARA.2 However, in a number of cases a fusion protein different from PML-RARA is expressed. The RARA gene has been consistently involved in these variant translocations. These include the t(11;17)(q23;q21) that expresses a PLZF-RARA fusion; t(5;17)(q35;q21) that encodes NPM-RARA; t(11;17)(q13;q21) that encodes NUMA-RARA; and der(17) with duplication of 17q21.3-q23 that fuses STAT5b to RARA (reviewed in Redner3). These variant rearrangements are rare; fewer than 20 cases of the PLZF-RARA variant have been reported; only four cases of NPM-RARA; and one each of NUMA-RARA and STAT5b-RARA. Nevertheless, these variant translocations hold great importance as ‘experiments of nature’ and serve as tools to identify common biologic pathways that truly underlie development of the APL phenotype.

We here report a novel case of APL with fusion of RARA with a locus on 3p25. A 72-year-old man presented with a white blood cell count of 20.4 × 109/l, hemoglobin 10.3 g/l, and platelets 22 × 109/l. The peripheral blood white cell differential revealed 20% polymorphonuclear leukocytes, 4% bands, 15% lymphocytes, 19% monocytes, 34% blasts, 1% promyelocyte, 6% myelocytes, and 1% metamyelocytes. The majority of blasts demonstrated reniform or bilobed nuclear features. Auer rods were seen in many blasts along with prominent cytoplasmic granulation. The bone marrow biopsy was hypercellular (approximately 80%), with 88% blasts, 1.7% promyelocytes, 0.3% myelocytes, 0.3% polymorphonuclear leukocytes, 0.3% eosinophils, 3% monocytes, 0.3% pronormoblasts, 3.7% normoblasts, and 2.3% lymphocytes. The blasts were similar morphologically to those seen in the peripheral blood. The blasts were positive for chloroacetate esterase staining and were negative for staining with nonspecific esterase. Flow cytometry studies performed on the bone marrow showed the blasts to be positive for CD117, CD13 and/or CD33, partial CD15, CD33, and strongly myeloperoxidase positive. The blasts were negative for expression of CD34 and HLA-DR. The morphologic findings along with the flow cytometry results were consistent with a diagnosis of APL.

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Authors and Affiliations

  1. Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    R L Redner & C Evans

  2. Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA

    L C Contis, F Craig & S Shekhter-Levin

  3. Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA

    M E Sherer & S Shekhter-Levin

  4. Pittsburgh Cytogenetics Laboratory, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    M E Sherer & S Shekhter-Levin

  5. University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    R L Redner, L C Contis, F Craig, C Evans, M E Sherer & S Shekhter-Levin

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  1. R L Redner
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  2. L C Contis
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Correspondence to R L Redner.

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Redner, R., Contis, L., Craig, F. et al. A novel t(3;17)(p25;q21) variant translocation of acute promyelocytic leukemia with rearrangement of the RARA locus. Leukemia 20, 376–379 (2006). https://doi.org/10.1038/sj.leu.2404062

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