biphenotypic acute leukemias ( bal ) are rare and account for less than 4% of all cases of acute leukemia . in 1995 , the european group for the immunological classification of leukemias ( egil ) proposed immunological criteria for the classification of acute leukemias , including a scoring system for the definition of bal . the most frequent cytogenetic abnormalities described in bal patients include the philadelphia chromosome and the presence of 11q23 rearrangement . the t(15;17)(q22;q12 ) is almost always associated with the morphological picture of acute promyelocytic leukemia ( apl ) . at the genetic level , this translocation creates the promyelocytic ( pml)-retinoid acid receptor  ( rar ) and rar-pml fusion genes . in clinical practice , the identification of the t(15;17 ) translocation predicts sensitivity to all - trans - retinoic acid ( atra ) . we encountered an extremely rare case of bal with t(15;17 ) lacking pml / rar rearrangement . the treatment was effective with chemotherapy for all and gemtuzumab ozogamicin ( go ) without atra . a 55-year old japanese woman was referred to our hospital with elevated white blood cell ( wbc ) counts with blasts . her laboratory data on admission showed rising wbc counts ( 13.410/l ; 76% blasts , 1% band , 6% segmented , 16% lymphocytes , 1% monocytes ) with anemia and thrombocytopenia ( hemoglobin 9.3 g / dl and platelets 11010/l ) . lactate dehydrogenase was slightly raised to 367 iu / l ( normal range 120 - 245 ) . we detected differences in the size of the blasts , corresponding to an abnormal lymphocyte - like cell population with a high nuclear / cytoplasmic ( n / c ) ratio , but without granules in the cytoplasm ( figure 1 ) . morphological findings were compatible with acute lymphoblastic leukemia ( all - l2 , fab classification ) . immunophenotype with double - color flow cytometry showed positivity ( > 30% ) for cd19 ( 90.8% ) , cd22 ( 45.4% ) , cd79a ( 92.4% ) , cd13 ( 40.9% ) , cd33 ( 94.6% ) , cd34 ( 95.8% ) and hla - dr ( 93.8% ) . the use of the egil scoring system revealed 5 points for b - lymphoid lineage and 2 points for myeloid lineage . chromosomal analysis with g - banded karyotype of the bone marrow cells showed 46 , xx , t(4;12)(q21;p11 ) , t(15;17)(q22;q12 ) in all 24 metaphase spreads ( figure 2a ) . fluorescence in situ hybridization ( fish ) performed on interphase nuclei using an lsi pml / rar dual color , dual fusion translocation probe ( vysis , usa ) showed two separate pml and rar signals ( figure 2b ) in 1000 interphase nuclei and all metaphases analyzed . the patient was initially treated with the japan adult leukemia study group ( jalsg)-all202 chemotherapy protocol ( table 1 ) and induction for all treatment was completed . the bone marrow aspirate at the end of the induction phase revealed hematologic complete remission ( cr ) . after the consolidation phase i ( with a high dose of cytarabine ) , thereafter , we administered a single dose ( 9 mg / m ) of gemtuzumab ozogamicin ( go ) , an anti - cd33 antibody conjugate , independent of the jalsg protocol , and subsequently , completed the course until consolidation phase v. furthermore , we continued maintenance phase therapy using the jalsg protocol until two years after the onset of disease , during which time we administered go ( 6 mg / m ) twice . at present , 1.7 years after the end of chemotherapy , the patient has remained in hematologic first cr during the over 3.7 years follow up . immunophenotype with double - color flow cytometry showed positivity ( > 30% ) for cd19 ( 90.8% ) , cd22 ( 45.4% ) , cd79a ( 92.4% ) , cd13 ( 40.9% ) , cd33 ( 94.6% ) , cd34 ( 95.8% ) and hla - dr ( 93.8% ) . the use of the egil scoring system revealed 5 points for b - lymphoid lineage and 2 points for myeloid lineage . chromosomal analysis with g - banded karyotype of the bone marrow cells showed 46 , xx , t(4;12)(q21;p11 ) , t(15;17)(q22;q12 ) in all 24 metaphase spreads ( figure 2a ) . fluorescence in situ hybridization ( fish ) performed on interphase nuclei using an lsi pml / rar dual color , dual fusion translocation probe ( vysis , usa ) showed two separate pml and rar signals ( figure 2b ) in 1000 interphase nuclei and all metaphases analyzed . the patient was initially treated with the japan adult leukemia study group ( jalsg)-all202 chemotherapy protocol ( table 1 ) and induction for all treatment was completed . the bone marrow aspirate at the end of the induction phase revealed hematologic complete remission ( cr ) . after the consolidation phase i ( with a high dose of cytarabine ) , the patient experienced the complication of septic shock with acute phlegmonous gastritis . thereafter , we administered a single dose ( 9 mg / m ) of gemtuzumab ozogamicin ( go ) , an anti - cd33 antibody conjugate , independent of the jalsg protocol , and subsequently , completed the course until consolidation phase v. furthermore , we continued maintenance phase therapy using the jalsg protocol until two years after the onset of disease , during which time we administered go ( 6 mg / m ) twice . at present , 1.7 years after the end of chemotherapy , the patient has remained in hematologic first cr during the over 3.7 years follow up . according to the 2001 who classification and egil scores , which are the established diagnostic criteria for bal , a diagnosis of bal in our patient was confirmed . this is due to scoring ( > 2 points ) that includes blasts of b - lymphoid lineage consistent with morphological all , as well as myeloid lineages such as cd13 and cd33 . however , in the 2008 who classification , the criteria for myeloid lineage were revised so that mpo or monocytic differentiation was a necessary condition . acute leukemia with dual phenotype was classified in a new category called mixed phenotype acute leukemia ( mpal ) . according to these diagnostic criteria , about one - third of cases of bal have the philadelphia chromosome , and some cases are associated with the t(4;11)(q21;q23 ) or other 11q23 abnormalities . we observed 4q21 abnormalities ( af4 gene ) in our patient , but could not confirm 11q23 abnormalities . although a case of apl by the g - banding method with the insertion of pml - rar fusion gene in 4q21 was previously reported , we could find no evidence of a relationship between 4q21 abnormalities and t(15;17 ) in our patient . although t(15;17 ) and pml / rar fusion are regarded as highly specific for apl , they have only been reported in rare cases of aml that were neither morphologically nor immunophenotypically consistent with apl . moreover , scolnik et al . reported a case of a 7-year old girl who received a combined therapy ; she was first treated with all protocols , changing to aml protocols in combination with atra in a second instance . the localization of breakpoints at pml / rar had not been clearly defined , being variously identified as 15q22-q24 and 17q11-q21 . more exactly , the precise location of the rar breakpoint had been the subject of variable reports in the literature . the pml / rar breakpoint was unified to 15q22 and 17q12 according to the 2001 who classification . before 2001 , 3 other cases of t(15;17 ) translocations similar to our case had been described , where the pml / rara rearrangement was absent by fish , although the chromosomal breakpoints were 15q22-q24 and 17q11-q21 . in these cases ( including ours ) , the break- points are considered to be subtly different from pml / rar. the previously reported 3 cases were non - apl ( m2 , m2 , m5a ) , with low sensitivity to chemotherapy ( atra was administered in 2 cases without effect ) , and all the patients had died within 1.5 years . recently , chemotherapy for all has been shown to be effective for mpal . the prognosis appears to be unfavorable , particularly in adults ; the occurrence of the t(4;11 ) or the philadelphia chromosome are particularly unfavorable prognostic findings . on the other hand , noted cr rates of 78% and an overall survival probability at two years of 60% in 31 adult bal patients , excluding t(9;22)(q34;q11)-positive cases , undergoing mainly hyper - cvad therapy ( hyperfractionated cyclophosphamide , vincristine , doxorubicin , and dexamethasone combined with high - dose cytarabine and methotrexate ) . on the basis of the morphology and immunophenotype of the blasts at onset , we determined our case to be bal , also consistent with cd33 strongly positive all . as such , we initially managed the patient with induction chemotherapy for all and achieved cr . we considered cd33-positive minimal residual disease and added go to the standard jalsg - all protocol as consolidation and maintenance treatment . there was no evidence of recurrence , and this management approach achieved and maintained a first cr of over 3.7 years . we believe that not only chemotherapy for all , but also a low , divided dose of go , was effective in treatment . in conclusion , we report an extremely rare case of bal with t(15;17 ) lacking pml / rar rearrangement . the clinical course of this patient is proceeding satisfactorily with chemotherapy as for all and go .
biphenotypic acute leukemias ( bal ) account for less than 4% of all cases of acute leukemia . 
 philadelphia chromosome and 11q23 rearrangement are the most frequently found cytogenetic abnormalities . since t(15;17 ) is almost always associated with acute promyelocytic leukemia , t(15;17 ) in bal cases is extremely uncommon . 
 we report here a rare and instructive case of bal with t(15;17 ) and the successful treatment approach adopted . 
 a 55-year old woman was referred to our hospital for an examination of elevated white blood cell ( wbc ) counts with blasts ( wbc 13.4109/l ; 76% blasts ) . 
 the blasts with acute lymphoblastic leukemia ( all - l2 , fab ) morphology co - expressed b - lymphoid and myeloid lineages , and a cytogenetic study revealed 4q21 abnormalities and t(15;17 ) . 
 however , promyelocytic - retinoid acid receptor  rearrangement was not detected by fluorescence in situ hybridization on interphase nuclei . 
 our patient was treated with chemotherapy for all and gemtuzumab ozogamicin without all - trans - retinoic acid , and has remained in hematologic first complete remission for more than 3.7 years .