APL-The Age-Old Harlequin: Do We See it All?

Abstract

Dear Sir, Acute promyelocytic leukemia (APL) is a unique type of acute myeloid leukemia characterized by distinct cytomorphological features, immunophenotype, molecular rearrangement t(15;17) involving the PML and RARa genes and a very good response to all-trans retinoic acid (ATRA) [1]. However in rarity of cases, no evidence for rearrangement of RARa is found indicating that alternative mechanisms could mediate the differentiation block that typifies this disease. Here we describe a case of APL, with classical morphological and immunophenotypic features, which was of interest because of presence of isochromosome(17) along with the absence of rearrangement of RARa. APL hence always proves to be a harlequin that takes various molecular and morphological masquerades. An 11-year-old male child presented at our centre with high grade fever and cervical lymphadenopathy for 2 months duration. Baseline laboratory investigations showed TLC of 14,800/lL with 85 % abnormal promyelocytes with hemoglobin of 7.7 gm% and platelet count of 20,000/lL (Fig. 1). On flow cytometry, abnormal promyelocytes were positive for cMPO, CD117, CD13, CD33, CD9, CD64 and CD65. These cells were negative for CD34, CD2, cCD79a, CD3, CD11b, CD18, CD14, CD38, CD56, CD4 and HLA-DR. A diagnosis of APL was made and genetic studies performed. RT-PCR was negative for PML–RARa fusion transcript. Metaphase karyotyping revealed 45–48,XY,i(17)(q10), -6, ?8, -14, -21, ?21[cp10] (Fig. 2). ATRA based combination chemotherapy with Daunomycin was given. Patient was in morphological remission at day 28 of induction and at the end of first consolidation cycle. After completion of consolidation phase, patient received maintenance therapy and is doing well at a follow up of 4 months. APL can have varied clinical and morphogenetic presentation. Besides the conventional reciprocal translocation t(15;17)(q22;q21) disrupting the PML and RARa genes, other chromosomal abnormalities such as t(11;17) (q23;q21), t(5;17)(q35;q12–21), t(11;17)(q13;q21) and der(17) are also observed in APL whereby RARa is fused to the PLZF, NPM, NuMA, and STAT5b genes, respectively. An isochromosome of the long arm of the derivative chromosome 17 is rarely observed in APL patients. However our case is further rare as no evidence for rearrangement of RARa was found. Only 3 such cases have been reported previously in literature [2–4]. Two of these three patients responded poorly to therapy and died within a year [2, 4]. The prognosis of third cases is not known [3]. Our case responded to standard doses of ATRA and BM was in morphological remission at day 45. Consolidation and maintenance was uneventful and is doing well on maintenance. The present case hence highlights the importance of immune-morphological and genetic basis of APL. These cases can still be managed by ATRA which shows that differentiation block by any molecular mechanism in APL can still be overcome by its therapeutic doses as in our case. Management and prognosis of such patients remains unknown as there is not much literature on management of such patients. The lack of independent prognostic value of additional chromosomal abnormalities in APL does not support the use of alternative therapeutic strategies when such abnormalities are found [5]. ATRA however remains A. Misra S. Soni A. Dutta R. Kumar A. Chopra (&) Laboratory Oncology, BRA IRCH, AIIMS, New Delhi, India e-mail: chopraanita2005@gmail.com