acute promyelocytic leukemia ( apl ) is one of the most characteristic subtypes of aml in which abnormal promyelocytes predominate within peripheral blood or bone marrow .
also , t(15;17)(q22;q21 ) shows a characteristic chromosomal translocation in apl , observable in 70 - 90% of apl patients .
owing to all trans - retinoic acid ( atra ) combined with chemotherapy , apl has one of the highest cure rates of all types of aml .
seventy to eighty percent of newly diagnosed apl patients with the pml - rara rearrangement are cured or under long - term remission , yet some of them have a poor prognosis [ 2 - 5 ] . because cytogenetics is one of the most powerful prognostic factors for the outcome of aml , cytogenetic abnormalities can cause change in treatment response , relapse , and clinicopathological characteristics .
incidence of secondary cytogenetic abnormalities has been observed in ~40% of apl cases , but their prognostic significance is still unclear [ 5 - 7 ] .
about 1% of the reported secondary cytogenetic abnormalities in apl patients are ider(17)(q10)t(15;17)(q22;q12 ) , an infrequent type of additional recurrent chromosomal abnormality , according to a recent study . however , ider(17)(q10)t(15;17 ) associated with the pml - rara rearrangement in microgranular variant apl is even more rare . as far as we know ,
only 2 cases of the ider(17)(q10)t(15;17 ) abnormality in microgranular apl have been previously reported [ 8 , 9 ] . here
, we describe an unusual microgranular apl case associated with ider(17)(q10)t(15;17 ) , identified by both conventional cytogenetics and fish analyses at the initial diagnosis .
a 59-yr - old woman who had previously been diagnosed with cerebral infarction was brought to our hospital due to right side weakness in november 2007 .
the initial complete blood count showed pancytopenia , hb level of 9.9 g / dl ( reference range 12 - 16 g / dl ) , platelet count of 83,000/l ( reference range 150,000 - 350,000/l ) , and white blood cell count of 1,000/l ( reference range 4,000 - 10,000/l ) .
bone marrow aspiration showed a hypercellular marrow replaced by increased promyelocytes with a paucity or absence of granules , accounting for 36% of all nucleated cells ( fig .
the results of special staining of bone marrow specimens were as follows : myeloperoxidase , positive ; periodic acid schiff , negative ; nonspecific esterase , negative .
flow cytometric analysis was conducted and showed that the blasts were positive for cd13 ( 91.1% ) , cd33 ( 83.9% ) , cd117 ( 59.2% ) , cd2 ( 43.9% ) , and cd45 ( 25.4% ) , and negative for hla - dr ( 3.4% ) , cd3 ( 1.3% ) , cd7 ( 0.6% ) , cd10 ( 1.8% ) , cd14 ( 2.4% ) , cd19 ( 5.1% ) , cd34 ( 1.4% ) , cd41 ( 2.9% ) , cd56 ( 1.2% ) , and tdt ( 0.9% ) .
fish signals from pml - rara probes ( abbott molecular / vysis , des plaines , il , usa ) yielded the results of nuc ish(pml , rara)4(rara con pml3)[24/138 ] , ( pml , rara)6(rara con pml5)[14/138 ] , ( pml , rara)3(rara con pml2)[13/138 ] , consistent with the abnormal fusion signal patterns seen in 37% of the nuclei examined ( fig .
the patient was diagnosed with apl and treated with induction chemotherapy consisting of daunorubicin , cytosine arabinoside , and atra . after completing induction chemotherapy ,
follow up bone marrow examination in january 2008 showed no evidence of morphologically visible residual leukemia .
the concurrent karyotype analysis result was 46,xx in all analyzed cells ; and pml - rara fish showed " nuc ish ( pml , rara)2 " in which the abnormal signal pattern was not observed .
there was no evidence of a pml - rara fusion gene in the reverse transcriptase - pcr ( rt - pcr ) analysis .
as indicated by follow - up bone marrow biopsies conducted until september 2008 , the patient remained in complete remission . during this period
, the rt - pcr analysis did not show any signs of the pml - rara fusion gene while other cytogenetic studies also indicated normal findings .
apl is a distinct subtype of aml and constitutes about 5 - 8% of all cases of aml diagnosis . according to the 2008 who classification
, apl can be diagnosed when there is a t(15;17 ) or a pml - rara rearrangement , even if peripheral blood or bone marrow studies show less than 20% promyelocytes . as recently reported by manola et al .   and
our study group , the ider(17)(q10)t(15;17 ) , an isochromosomal abnormality that occurs on the long arm of ider(17)t(15;17 ) after reciprocal translocation of t(15;17 ) , is a relatively rare type of an additional recurrent cytogenetic abnormality that has been reported in 62 apl patients worldwide [ 8 - 13 ] . according to these studies , the influence of ider(17)(q10)t(15 ; 17 ) on the prognosis of adult apl patients
indeed , 4 previously reported apl cases in children were all related to poor prognosis [ 8 , 13 - 15 ] , inferring that a more close and careful interpretation is necessary for childhood apl cases .
what is interesting is that so far , reports of ider(17)(q10)t(15;17 ) from microgranular variant ( aml - m3v ) type are extremely rare .
out of 62 total cases , information on apl morphology type were available in 42 cases , and most of these cases ( 40/42 ) were of the hypergranular apl type , except for 2 cases that clearly indicated aml - m3v ( table 1 ) [ 8 , 9 ] .
therefore , further research is required to determine whether ider(17)(q10 ) and aml - m3v have a low association , and more careful observation should be conducted to prevent underestimating aml - m3v patients among ider(17)(q10)t(15;17 ) cases .
furthermore , double ider(17 ) ( q10)t(15;17 ) is so rare in the international public databases that only 2 cases of apl patients indicating double ider(17)(q10)t(15;17 ) chromosomal abnormalities have been reported ( table 2 ) [ 16 , 17 ] . in double ider(17)(q10)t(15;17 ) , a gene dosage effect is observed owing to chromosomal abnormalities such as the pml - rara fusion gene on chromosome 17 or the quadruplication of der(17q ) . in addition , since the deletion of the tumor suppressor gene tp53 occurs by the loss of 17p , further research is necessary to resolve the adverse prognosis of the apl group related to such copy number variations .
owing to the limited amount of clinical data in the literature , the relatedness between double ider(17)(q10)t(15;17 ) and an adverse prognosis is still unclear [ 16 , 17 ] . in the case of our patient
, it was hard to determine a strong association between the additional genetic aberration and prognosis because of the small clonal size of the " double ider(17)(q10)t(15;17 ) " abnormality .
nevertheless , at least from a diagnostic perspective and as indicated in the authors ' recent studies [ 13 , 18 ] , minimal residual disease detection using such multiple abnormal fusion signals through the pml - rara fish analysis in apl patients associated with ider(17)(q10)t(15;17 ) or double ider(17)(q10)t(15;17 ) would be considered to be a useful follow - up marker in clinical laboratories or hospitals .
additional study would contribute toward a better understanding of the influence of ider(17)(q10)t(15;17 ) on the prognosis , survival , and treatment response of such apl cases in adults or children . to the best of our knowledge
, however , this is the third case report of microgranular variant apl associated with ider(17)(q10)t(15;17 ) .
 we present a rare case of microgranular variant acute promyelocytic leukemia ( apl ) associated with ider(17)(q10)t(15;17)(q22;q12 ) of an old - age patient . 
 the initial chromosome study showed a 46,xx , del(6)(?q21q25),der(15)t(15;17)(q22;q12),ider(17)(q10)t(15;17)[10]/47,sl,+ider(17)(q10)t(15;17)[3]/46,xx[16 ] . 
 fish signals from a dual color dual fusion translocation pml - rara probe were consistent with the results of conventional cytogenetics . 
 because of the rarity of ider(17)(q10)t(15;17 ) in microgranular apl , further studies on both gene dosage effect of this chromosomal abnormality and the influence of ider(17)(q10)t(15;17 ) on clinical features such as prognosis , survival , and treatment response of apl cases are recommended . 