Acute Promyelocytic Leukemia with Cryptic PML-RARA Translocation and Del(9q) with CD56 Positivity: A Case Report

Case Report

Ann Hematol Oncol. 2017; 4(1): 1129.

Acute Promyelocytic Leukemia with Cryptic PML-RARA Translocation and Del(9q) with CD56 Positivity: A Case Report

El Jabbour TS, Dalvi SD*, Subik MK, Homan SM and Nazeer T

Department of Pathology, Albany Medical Center, USA

*Corresponding author: Dalvi SD, Department of Pathology, Albany Medical Center, 47 New Scotland Avenue, Albany, NY 12208, USA

Received: December 22, 2016; Accepted: January 24, 2017; Published: January 27, 2017


Acute promyelocytic leukemia (APL) is classically associated with t (15;17) and has a favorable prognosis upon immediate recognition and treatment. However, a small minority of APL cases shows cryptic translocations that are detected only by polymerase chain reaction (PCR). A high index of suspicion, based on peripheral blood or bone marrow morphology, flow cytometric data, and clinical features, is essential for the diagnosis of these cases. We suggest that in such cases with a high index of suspicion, a negative karyotype or FISH should be reflexed to PCR confirmation for detection of PML-RARA transcript. We present here a rare case of APL that is positive for PML-RARA only by PCR, hasdel(9q) as the sole cytogenetic abnormality, and is positive for CD56 on flow cytometry.

Keywords: Acute myeloid leukemia; Acute promyelocytic leukemia; PMLRARA; t(15;17)


Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML), which has been designated as AML-M3 in the old French-American-British (FAB) classification, and is currently classified by the WHO as AML with recurring genetic abnormalities (APL with PML-RARA). It makes up about 5-8% of cases of de novo AML [1], with roughly 600-800 cases seen yearly in the United States [2]. The disease is rapidly fatal if untreated, with death resulting from disseminated iintravascular coagulation (DIC) and hemorrhagic or thrombotic complications.

The presence of a specific reciprocal translocation t(15;17) (q22;q12) is the defining feature of this leukemia, that results in fusion of the promyelocytic leukemia (PML) gene on chromosome 15q22 with the retinoic acid receptor-α (RARα or RARA) gene on chromosome 17q12, resulting in a PML-RARA transcript. The translated protein product functions as a novel oncoprotein and leads to maturation arrest at the promyelocyte stage of myeloid differentiation, leading to accumulation of blasts and promyelocytes in the bone marrow. This t(15;17) is seen in approximately 98% cases of APL (classical APL) [3] and is detected by either conventional karyotyping or fluorescence in situ hybridization (FISH). A rapid response to all-trans retinoic acid (ATRA) that relieves the promyelocyte maturation arrest is a feature of these classical cases.

The vast majority of the remaining cases is negative by conventional karyotyping or FISH, but is positive for the presence of the PML-RARA transcript by RT-PCR. These cases are said to have a “cryptic” or “masked” translocation, and are still responsive to ATRA. Three isoforms of PML-RARA transcript have been described [2]:

However, a minority of cases are negative for PML-RARA translocation. Rather, these cases show variant translocations involving RARA with other partner genes including PLZF, NPM, NUMA, STAT5B, ZBTB16, PRKAR1A, FIP1L1, and BCOR. These cases are referred to as APL with variant RARA translocations and are often unresponsive to ATRA [1,4].

In addition to t(15;17), other chromosomal aberrations are detected in up to 50% of APL cases [2,5]. The clinical significance of these additional aberrations is controversial, with some studies demonstrating a poorer prognosis. The most frequent aberration described is trisomy 8, seen in 17% to 46% of cases [6-8]. Other anomalies described include del(9q), del(7q), abnormalities of chromosomes 1, 3, 6, trisomy 21, and isochromosome of long arm of derivative chromosome 17 originating from the t(15;17).

Case Presentation

MS is a 45-year old lady who was admitted to our hospital after falling from a chair due to pain and weakness in her lower extremities for the preceding 2 to 3 weeks. She also complained of menorrhagia and dizziness and noticed extensive bruising on the day of admission.

Complete blood count revealed hemoglobin of 8.1 g/dL; white blood cell count of 9.7x109/L; Platelet count of 9x 109/L. Her activated partial thromboplastin time was within normal limits on presentation (25 seconds; lab control 24-32 s), but gradually increased to 47 seconds during her 4-week hospital stay. Her prothrombin time was elevated on presentation (15.6 seconds; lab control: 9.8-11.8 seconds). Her fibrinogen was markedly decreased (62 mg/dL; lab normal range: 180-350 mg/dL). Examination of the peripheral smear revealed increased immature myeloid precursors with irregular cleaved nuclei, fine chromatin, inconspicuous nucleoli and moderate cytoplasmic granularity, with only occasional Auer rods detected. Bone marrow examination revealed 87% blasts and blast equivalents with similar morphology (Figures 1,2,3 and 4).