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ider(17)(q10)t(15;17) associated with relapse and poor prognosis in a pediatric patient with acute promyelocytic leukemia

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Abstract

Although acute promyelocytic leukemia (APL) has been regarded as a serious medical emergency associated with disseminated intravascular coagulopathy or subsequent mortality, it is now considered a curable leukemia that is particularly sensitive to treatment with all-trans retinoic acid combined with chemotherapy. However, it is not clear whether additional chromosomal abnormalities in APL patients directly influence the prognosis or treatment response. ider(17)(q10)t(15;17)(q22;q21) has mostly been reported in adult APL patients, and only three cases of pediatric APL associated with ider(17)(q10)t(15;17) showing poor prognosis have been described in the literature. Here, we report the close follow-up (clinical and laboratory) data of a pediatric APL case associated with ider(17)(q10)t(15;17). This patient had APL relapse from the same clone 15 months after morphological remission. Furthermore, despite subsequent chemotherapy, the patient died 16 months after the initial APL diagnosis. Although based on a limited amount of data (four pediatric APL cases), such results in pediatric APL patients may provide important insight into the relationship between ider(17)(q10)t(15;17) and poor prognosis. However, further well-designed case-control studies are necessary to determine the treatment response and prognosis in pediatric or adult APL patients with ider(17)(q10)t(15;17).

Introduction

Acute promyelocytic leukemia (APL) is a well-defined subtype of acute myeloid leukemia characterized by unique morphology of leukemic cells and the specific t(15;17), which is present in approximately 80% of APL cases [1], [2], [3]. The t(15;17) chromosomal translocation fuses the PML gene on chromosome 15 encoding a transcription factor with the retinoic acid receptor alpha (RARA) gene on chromosome 17, which is a member of a steroid hormone nuclear receptor family that is important for the regulation and control of both normal and malignant cellular differentiation and proliferation [3]. ider(17)(q10)t(15;17)(q22;q21), a variant cytogenetic abnormality among APL patients, has been reported only rarely in the literature. To our knowledge, 61 APL cases associated with ider(17)(q10)t(15;17) have been described to date [4], [5], [6], [7], [8], [9]. Despite several case series that assessed the influence of ider(17)(q10)t(15;17) on the clinical outcome of APL, conclusions remain unclear [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17]. Furthermore, most of the reported ider(17)(q10)t(15;17) cases were in adult APL patients.

Here, we describe a rare case of pediatric APL with ider(17)(q10)t(15;17) and trisomy 8, identified by both conventional cytogenetics and fluorescence in situ hybridization (FISH) analyses. We discuss the clinical course and close follow-up data of this patient, and we present a brief review of the literature for pediatric APL cases with ider(17)(q10)t(15;17).

Section snippets

Clinical presentation

A 13-year-old Korean boy who had previously been in good health was brought to Kyung Hee University Medical Center with easy bruising in June 2008. The initial complete blood count showed hemoglobin level of 8.2 g/dL (reference range 12–16 g/dL), platelet count of 26,000/μL (reference range 150,000–350,000/μL), and white blood cell count of 1,670/μL (reference range 4,000–10,000/μL) with 4% segmental neutrophils, 57% lymphocytes, and 39% promyelocytes. Analysis of bone marrow aspirate showed

Discussion

The ider(17)(q10)t(15;17) is a relatively rare type of an additional recurrent cytogenetic abnormality that has been reported in 61 APL patients worldwide [4], [5], [6], [7], [8], [9]. It is an isochromosomal abnormality that occurs on the long arm of der(17)t(15;17) after reciprocal translocation of t(15;17), and it shows three characteristic abnormal fusion signals with PML-RARA dual-color, dual-fusion translocation FISH probes. Generally, the cutoff level of commercially available

Acknowledgment

This research was supported by a grant KHU-20091411 from the Kyung Hee University Program for the Young Researcher in Medical Science.

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These authors contributed equally to this work and each is considered first author.

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