Medknow Publications on behalf of Indian Society of Human Genetics
Abstract
Acute promyelocytic leukemia (APL) is characterized by a reciprocal
translocation t(15;17)(q22;q21) leading to the disruption of
Promyelocytic leukemia (PML) and Retionic Acid Receptor Alpha (RARA)
followed by reciprocal PML-RARA fusion in 90% of the cases.
Fluorescence in situ hybridization (FISH) has overcome the hurdles of
unavailability of abnormal and/or lack of metaphase cells, and
detection of cryptic, submicroscopic rearrangements. In the present
study, besides diagnostic approach we sought to analyze these cases for
identification and characterization of cryptic rearrangements, deletion
variants and unknown RARA translocation variants by application of
D-FISH and RARA break-apart probe strategy on interphase and metaphase
cells in a large series of 200 cases of APL. Forty cases (20%) had
atypical PML-RARA and/or RARA variants. D-FISH with PML/RARA probe
helped identification of RARA insertion to PML. By application of
D-FISH on metaphase cells, we documented that translocation of 15 to 17
leads to 17q deletion which results in loss of reciprocal fusion and/or
residual RARA on der(17). Among the complex variants of t(15;17),
PML-RARA fusion followed by residual RARA insertion closed to PML-RARA
on der(15) was unique and unusual. FISH with break-apart RARA probe on
metaphase cells was found to be a very efficient strategy to detect
unknown RARA variant translocations like t(11;17)(q23;q21),
t(11;17)(q13;q21) and t(2;17)(p21;q21). These findings proved that
D-FISH and break-apart probe strategy has potential to detect primary
as well as secondary additional aberrations of PML, RARA and other
additional loci. The long-term clinical follow-up is essential to
evaluate the clinical importance of these findings