A case of acute promyelocytic leukemia variant with derivative chromosome 3 der(3)t(3;8) associated with 8q partial gain

Filomena Nozza,Luciana De Luca,Luciana Possidente,Francesco La Rocca,Stefania Trino,Vitina Grieco,Fiorella D’Auria,Pellegrino Musto,Gabriella Vona

doi:10.1186/s13039-019-0445-1

Abstract

BackgroundAcute promyelocytic leukemia (APL) is characterized by fusion of PML/RARα genes as a result of t(15;17)(q24;q21). APL is now one of the curable hematological malignancies thanks to molecularly targeted therapies based on all-trans retinoic acid (ATRA) and arsenic trioxide (ATX). Extramedullary (EM) relapse is a rare event in APL, ear involvement being even more infrequent, with only six cases so far described. About 30–35% of patients with newly diagnosed APL have additional cytogenetics abnormalities, whose prognostic significance is still controversial. The most common additional aberration is trisomy 8 or partial gain 8q.Case presentationWe describe here a novel unbalanced translocation der(3)t(3;8)(q29;q23.3-q24.3) associated with 8q partial gain in a 41 year-old man affected by APL in molecular remission after first line treatment, who had a responsive EM relapse in the auditory canal.ConclusionsEM relapse is a rare event in APL and ear involvement is even more infrequent. To our knowledge, this is the first reported case of APL with a new der(3)t(3;8)(q29;q23.3-q24.3) and 8q partial gain associated with t(15;17)(q24;q21). Despite the recurrence of the disease at EM level, the clinical outcome of this patients was favorable.

Highlights

Acute promyelocytic leukemia (APL) is characterized by fusion of Promyelocytic Leukemia (PML)/RARα genes as a result of t(15; 17)(q24;q21)
EM relapse is a rare event in APL and ear involvement is even more infrequent
At time of EM relapse, bone marrow (BM) karyotype was 46,XY and both fluorescence in situ hybridization (FISH) and quantitative PCR analyses were negative for PML/RARα fusion gene

Summary

Introduction

Acute promyelocytic leukemia (APL) is characterized by fusion of PML/RARα genes as a result of t(15; 17)(q24;q21). About 30–35% of patients with newly diagnosed APL have additional cytogenetics abnormalities, whose prognostic significance is still controversial. Acute Promyelocytic Leukemia (APL) is a subtype of Acute Myeloid Leukemia (AML), characterized by fusion of Promyelocytic Leukemia (PML) and Retinoic Acid Receptor Alpha (RARα) genes as a result of t(15;17)(q24.1; q21.2), which can be seen in up to 90% of APL cases [1]; in a minority of patients, it may be cryptic or results from complex cytogenetic rearrangements other than t(15;17) [2]. About 30–35% of patients with newly diagnosed APL harbor additional cytogenetics abnormalities, whose prognostic significance is still controversial [6]. In APL the most common additional aberration is trisomy 8 or partial gain 8q, which could induce a c-myc gene dosage effect [7, 8]. Among the EM sites, ear involvement is infrequent and small case series have been described [18,19,20,21,22]

Methods

Results

Conclusion