Introduction
Acute promyelocytic leukemia (APL) is a subtype of acute myeloid
leukemia (AML) that has a distinctive molecular pathophysiology and
clinical manifestations. It is cytogenetically characterized by
reciprocal translocation of promyelocytic leukemia (PML) gene at
chromosome 15 and retinoic acid receptor alpha (RARα) gene at chromosome
17 that leads to the termination of maturation at the promyelocyte stage
[1,2]. Prior to the introduction of all-trans retinoic acid (ATRA)
and arsenic trioxide (ATO), APL was the most fatal subtype.
Subsequently, therapy with ATRA and ATO has remarkably improved the
outcome of APL patients [1,2]. The long-term survival rate is ≥95%,
yet refractory/relapsed disease is still seen in around 5% of patients
[1].
FLT3 (fms-like tyrosine kinase 3), located on human chromosome 13q12-q13
is a cell membrane-expressed proto-oncogene that belongs to the tyrosine
kinase receptor family. The most common activating mutation in FLT3 gene
that occur in leukemia is internal tandem duplication (ITD) in exon 14
and 15 of the gene [3]. FLT3-ITD mutations have a significant
incidence rate in cases with APL ranging from 12 to 38% [4]. The
role of FLT3-ITDs in APL as a prognostic factor for long-term outcome
has not yet been clarified and the significance of these genetic
alterations remains controversial. FLT3-ITDs have been associated to a
variety of characteristics in APL including high while blood cell (WBC)
count, short bcr-3, or microgranular morphology (M3v) [1].
Here, we present a rare case of short isoform of PML-RARα and FLT3-ITD
with characteristics of variant APL in terms of elevated WBC count,
morphology and immunophenotype.