Coexistence of t(15;17) and t(15;16;17) detected by fluorescence in situ hybridization in a patient with acute promyelocytic leukemia: A case report and literature review

Abstract

Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q21), which results in the fusion of the promyelocytic leukemia (PML) gene at 15q22 with the retinoic acid α-receptor (RARA) gene at 17q21. The current study presents the case of a 54-year-old female with APL carrying the atypical PML/RARA fusion signal due to a novel complex variant translocation t(15;16;17)(q22;q24;q21), as well as the classical PML/RARA fusion signal. Subsequent array comparative genomic hybridization revealed somatic, cryptic deletions on 3p25.3, 8q23.1 and 12p13.2-p13.1, and a duplication on 8q11.2; however, no genetic material loss or gain was observed in the breakpoint regions of chromosomes 15, 16 or 17. To the best of our knowledge, this is the first report of the coexistence of two abnormal clones, one classical and one variant, presenting simultaneously in addition to cryptic chromosome segmental imbalances in an adult APL patient.

Treatment Outcome and the Genetic Characteristics of Acute Promyelocytic Leukemia in Children in Poland From 2005 to 2018

“…There are a number of studies concerning the alternate translocation in APL; however, little is still known about the complex variant translocations in APL (22,23). Both 4, 15, 17, and 15, 16, 17 translocations have been described by other authors (4,6,22,23), but the translocation found in our patient involving four chromosomes 4, 15, 16, and 17 has not been reported before.…”

“…Variant translocation described as simple translocation involving chromosome 15 or 17 with any other chromosomes or complex translocations characterized by the involvement of additional chromosomes in addition to chromosomes 15 and 17 (4)(5)(6)(20)(21)(22)(23)(24) was found in two patients in the analyzed group. In one of them, t(11;17) (q23;q12) was identified, and in the second complex, translocation involving chromosomes 4, 15, 16, and 17 was found.…”

“…Two different variant APL translocations involving chromosomes 11 and 17 were described before, t(11;17)(q23;q21) producing ZBTB16-RARA (formerly PLZF-RARA) fusion gene and t(11;17)(q13;q21) generating NUMA/RARA (20,22). In cases of APL with t(11;17)(q23q21), there is evidence of resistance to ATRA and ATO both in vivo and in vitro, particularly in those patients who have the reverse rearrangement RARα-PLZF (20), while patients with t(11;17)(q13;q21) have better prognosis (22).…”

Genetic Pathway in the Pathogenesis of Therapy-Related Myeloid Neoplasms: A Literature Review

“…They share breakpoints between the PML and RARA genes and form a reciprocal translocation, PML–RARA and RARA–PML. This fusion induces further development of t-MN [ 61 ].…”

A simple surface plasmon resonance biosensor for detection of PML/RARα based on heterogeneous fusion gene-triggered nonlinear hybridization chain reaction

“…Some conventional methods have been reported for detection of PML/RARα, such as flow cytometry 4 , real-time quantitative reverse transcription PCR 5 , chromosome analysis 6 , fluorescence in situ hybridization 7 , 8 and microarray-based techniques 9 , etc. However, these techniques suffer from the intrinsic limitations of complicated preparation, low specificity and expensive reagent 10 , 11 .…”