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Downloaded from http://journals.tums.ac.ir/ on Friday, April 27, 2012 ©201 Address: Corresponding * Author; E Original Article Original Iranian Hydrochemistry Key Words: - mail: olbrt wt ec ohr o mrv te rgoi o cidod AMLL childhood of prognosis results the of applications the improve to other each with collaborate problems many still are there Conclusion: treatment. remission complete T+B cases 14 the In visit. patients the of most in count cell blood of 7.57% for accounted immunology, morphology, Findings characteristics. University. Huazhong of Technology acute childhood of cases ad 185 from methods immunophenotyping and morphological Methods: study of childre for researches reported are some present, Only common. more At are adults in cells. AMLL myeloid and lymphoid misdiagnosed with involved easily character is dual AMLL a The of time. because same the at cells lymphoid and cells myeloid acute with Objective Abstract 2 1 1 . . by Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Medical of TehranUniversity Center, Medical Children’s Excellence, of Center Pediatrics by mitted to the Department of Pediatrics, Tongji Hospital, Tongji Pediatrics, of Department the to mitted ClinicalStudy [email protected] - TongjiHospital, Tongji Medical College, Huazhong University of Science Technology, and Wuhan 430 Technology,Wuhan ofHospital,Medic Tongji Pediatrics,Department ZhengzhouChildren y/y. mn te, ie ae rcie tetet Cneunl, css reached cases 6 Consequently, treatment. received cases nine them, Among Ly+/My+. Journal clinical characteristics of the childhood AMLL. childhood of the characteristics clinical Yao : : rm aur 20 t Jl 20, 4 ae o AL cide wr slce by selected were children AMLL of cases 14 2009, July to 2000 January From Acute mixed Acute oren ae o AL wr sree f screened were AMLL of cases Fourteen d of ong The Acute Pediatrics Received: Zhang diagnosis of AMLL should depend on the comprehensive evaluation of MICM. As MICM. of evaluation comprehensive the on depend should AMLL of diagnosis Mixed C) 1 case 1 (CR); of AMLL, 8 cases were B were cases 8 AMLL, of , , ′ s Hospital s 1 Volume - China , of Acute of Mixed lineage leukemia (AMLL) is characterized as the acute leukemia involved leukemia acute the as characterized is (AMLL) leukemia lineage Nov MD; LinaMD; pediatric - Lineage Leukemia Lineage are yoeeis n mlclr ( molecular and 18 2 that they are they that ,20 1 , ( Number concerning Zhengzhou 1 Tan 0 ct luei (L dansd n h rsac pro; white period; research the in diagnosed (AL) leukemia acute had ; FinalRevision: ; Medical 1 ; was normal, the average value average the normal, was Xiao 4 o cmlt rmsin 2 ae did cases 2 remission; complete not ), December , only based on based only China l ; ing ML i i vr ncsay ht h rese the that necessary very is it AMLL, Immunophenotyping records of all of records - lineage Leukemia - Zhang Ly+/ May 20 My+, 2 cases were T were cases 2 My+, 1 al College,and al ofScienceHuazhong University 2 1 28 , , PhD; Pages , 20 o 15 ae o aue ekma by leukemia acute of cases 185 rom the patients of one of patients the IM. h rt of rate The MICM). AMLL Tongji Medical College of Science and Science of College Medical Tongji 11 Haiyan : 5 ; ; Accepted: 2 Dec 1 - 5 cases were reviewed for clinical for reviewed were cases ; 25 Bone Wei 20 being n. 11 1 All rights reserved. rights All Therefore, Jul , Marrow Morphology Marrow ; Vol ; and - in Ly+/My+B, and 4 were 4 and Ly+/My+B, 1 Iran J Pediatr J Iran 31.0×10 hospital 0,20 . Qun 14Children h lmttos and limitations The 21 n 11 childhood (No o 030, China Hu* cmlt the complete t our . 9 /L 4 2 ), Pp: ), , MD, aim was to was aim rh units arch in the first the AMLL 5 ; 2 1 - 5 25 Downloaded from http://journals.tums.ac.ir/ on Friday, April 27, 2012 522 arw mas ee nlzd y Wright's by analyzed were cla smears marrow examinations morphology marrow Bone signed had hospital. our in Committee Ethics Institutional guardians the by or approved was study The consent. informed parents their after 12.0 male 12 University. Huazhong of Technology Hospital, Tongji Pediatrics, of by Department the to admitted selected were fr children methods immunophenotyping AMLL and morphological of cases Subjects: Subject infollowing. the reported are results the and analyzed were years admitt children clear. entirely not is prognosis and significance clinical of diagnosis the My+ALL or Ly+ANLL calling AMLL char types chemistry cell and biclonal morphological advised have researchers and conversion the into (including bilinear divided further be biphenotypic, can phenotype AMLL l of regarding characteristics to leuke According the acute for of system classification scoring immunological Leukemia a proposed of has the (EGIL) for Characterization Group European Immunological 1995. in established character. dual a cri as cells myeloid and lymphoid with involved and leukemia, acute the in time same the at cells lymphoid and myeloid recent recogni in years leukemia of type gradually rare a as been established immunophenotyping has of (AMLL) use mixed acute wide clinic, in technology the With Introduction om 185 cases of childhood acute leukemia (AL) leukemia acute childhood of cases 185 om Therefore, the clinical data of 14 cases of AMLL of cases 14 of data clinical the Therefore, ei fr h danss of diagnosis the for teria sfcto cut, and counts, ssification ma 7 (mean [1] s . t s hrceie by characterized is It and 2 female 2 and ogi eia Clee f cec and Science of College Medical Tongji s rm aur 20 t Jl 20, 14 2009, July to 2000 January From nie epeso ad el source, cell and expression antigen and ) ed to our hospital during nearly 10 nearly during hospital our to ed yea ceitc t spot NL of ANLL support to acteristics AMLL Methods rs. s ains nee te study the entered Patients ; ages of patients were 1.5 were patients of ages ; s very is - type) had AMLL xsec of existence - lineage leukemia lineage ifcl, n its and difficult, tiig exami staining [2] [1] uei cells eukemia As, other Also, . . hr were There u i fact in But ae been have Consensus e and zed : acute Bone mia. - - , 00 cls i te tnad airto of calibration standard the via cells 10000 tube Each light. cytometer flow usi measured were were PBS. ml samples 0.5 PBS added then room staining; times, 3 at washed after lysine, 10min erythrocyte ml temperature 2 added then μ Becto from Company) Dickinson purchased (all antibodies, labeled (PE) (50uL fluorescent blood peripheral Immunophenotyping types. to referenced (PAS) staining glycogen and (NAP) staining phosphate fluoride, sodium and (POX) non of increase for includi nations, ML rm 8 A css cone fr 7. for accounted cases AL 185 from AMLL features Clinical Findings (RT reaction chain polymerase gene cells take was gene Fusion human by analyzed was karyotype the (87.5 of method heated h. 24 for cultured heparin with Chromosome ( expression antigen positive is includ HLA markers antigen cell stem while CD15; CD14, CD33, CD13, include antigens CD include lineage T CD22; CD20, CD19, CD10, include monoclonal lineage B of antibodies The cells. immature the calculate to analyzed was antigens cell hematopoietic of rate calibration discerning by virt In analysis. sphere instruments micro fluorescent l reaction tube, and 4 and tube, reaction l - Clinical Study of Acute Mixed Acute of Study Clinical DR. The standard of leukemia cells diagnosis cells leukemia of standard The DR. prtnu chl peritoneum / ee eaae by separated were genet detected n. leukemia cells, the positive expression positive the cells, leukemia isothiocyanate T . ics : e oe arw li mononuclear fluid marrow bone he Cellquest 2 analysis: g niiin et NE n NAF and (NSE test inhibition ng - nomenclature. B UA o b te 8n laser 488nm the by Co) USA (BD e f D5SC aig av to naive gating CD45/SSC of ue m bn mro wt heparin with marrow bone ml 3 and was : The - y ees transcription reverse by specific esterase by peroxides by esterase specific oren ae o childhood of cases Fourteen FAB criteria to determine the determine to criteria FAB which were added to the 20 the to added were which eie to revised : phytohemagglutinin R ℃ rpyl rti ( protein orophyll ℃ - otae a ue for used was software band specimens marrow Bone response for 20 for response - ) (Wright stain (Wright ) ficoll lineage Leukemia lineage ) (FITC) Bon , D, D; myeloid CD7; CD5, 3, ee eetd by detected were ing ng - etohl alkaline neutrophil ≥20%). marrow e PCR). liquid h international the comdt to accommodate was ASa model FACScan / ed phycoerythrin used and ; D4 and CD34 Y ing - Zhang 30 min; 30 Pre l the All by the by fusion ) 57%. , and , were - , et al ,et CP) or n ) - Downloaded from http://journals.tums.ac.ir/ on Friday, April 27, 2012 hoooe raae n 1 ae f mixed of examined case were cases 1 Five anomalies. and centric breakage of case chromosome 1 translocation, chromosome of cases cases 4 2 abnormalities, structural diploid. with found were hyper of case 1 chromosomes, were cases 2 gene. fusion and chromosomes AMLL in analyzed gene fusion and Chromosomes HLA and 2 cases was expression positive CD34 expression. positive CD15 of cases 2 and expression, positive antigen C of cases 5 expression, positive CD14 of cases Myeloid 6 expression, positive CD13 of cases 7 were there expression. which in cases, 14 the in CD5 positive was expression of 3 expression, cases positive CD3 of cases 4 and cases, w CD7 of expression Positive co and cases 2 in was lineage T and myeloid of expression and positive, cases cases and lineage B and myeloid of expression double T+B T of cases cases 8 that Th cases. 14 the all for performed was Immunophenotype cells blast consisted the on only. AMLL as morphology diagnosed were cases 4 Other myeloid acute of case of cases 2 (M2), leukemia myeloid acute of cases 3 including non 1 cases, 4 In cells marrow bone of typing morphology FAB ×10 80.14×10 was count average (37 g/L 68.27 was hemoglobin 31.0×10 count mean a and normal, was cases 14 in or gum cases hepatomegaly nodes fever of (64.29%) manifestation clinical had cases male were cases Twelve Iran J Pediatr; Vol 2 Vol IranJPediatr; - 9 - lymphoblastic leukemia ( leukemia lymphoblastic /L, while /L, y/y biphenotypic Ly+/My+ T had - +B xrsin f T+B of expression a found was . - - cases CD19 positive CD19 of Ly+/My+ biphenotypic. In B antigens B In biphenotypic. Ly+/My+ acute monotypic leukemia (M5), and 1 and (M5), leukemia monotypic acute y/y bpeoyi, n 4 ae of cases 4 and biphenotypic, Ly+/My+ in were skin 68 t 99.9% to 36.8% ae a L, n 3 ae L2; cases 3 and L1, was case , in 1 2 cases more than 100×109 than more cases 2 5 (No - nagmn of enlargement 7 cases on anra i nme of number in abnormal found cases 2 DR positive expression in 7 cases. in expression positive DR (35.71%) bleedi ( 4 f B of 166.5 ); , n 4 ae b cases 14 In : Dec Immunophenot 12 - 9 - 20 it oatc ekma (M4). leukemia monastic L Te vrg vle of value average The /L. y/y bpeoyi, 2 biphenotypic, Ly+/My+ ng. ± expression s 11 was below 50×10 was 1.34 Two . - (85.71%) cases W D2 oiie The positive. CD22 y/y i 4 cases. 4 in Ly+/My+ ANLL) were 6 cases, 6 were ANLL) hite count cell blood hite type )×10 s en n l the all in seen as - aeae 73.73%) (average 0 gL ad the and g/L) 102 uefca lymph superficial (71.43%) : splenomegaly . 9 i cases Six , /L css had cases 8 n marrow one 3 cases 3 ypic analysis ypic 9 in , cases L (0 /L is for showed /L cases 8 seen 9 female , fusi /L. - CD10 acute were 318) in with D33 had 5 ; on , 8 , in 9 4 : didn't complete (after T case 1 B were cases 5 the complete not CR, of cases 6 did In CR. missing case 1 , cases 2 and CR achieved cour first the After and (all ARTA etoposide), cytarabine, (daunorubicin, DAE L Ara (daunorubicin, DA received cases 3 course. daunorubicin, (vincristine, asparagine VDLP received chemotherapy receive parent their of income enough sequelae and Chemotherapy rearrangements. gene ETO, MLL cases 3 gene, our and c kidney nodes, of lymph and infiltration enlarged , pain, obvious cell, blood white of count we AMLL of characteristics the with account L2, account M2, AML leukemia observed most the was L2 cellular ALL, was the AMLL When of performance rare. were M5 and M4 while AML and AML was AMLL of morphology cellular The literature. series 20% than more leukemia acute of 7% not is clear mechanism the now, to up But cells. stem hematopoietic pluripotent from arise may it that characteristics biological was which My+ALL, and Ly+AML lines. as same cell the not was lymphoid AMLL and lines cell myeloid with AMLL Discussion series [4] achieve 2 was 7.57%, which 7.57%, was [7] . The incidence of AMLL of incidence The . i a ae id f ct luei involved leukemia acute of kind rare a s - 9 . hmteay and chemotherapy, - However, the clinical features of AMLL in AMLL of features clinical the However, - Ly+/My+ remission trans retinoic acid) + DAE + acid) retinoic trans years ee o cnitn wt te above the with consistent not were ing literature n dxmtaoe i te first the in dexamethasone) and rdcd with produced - complete had M2 was the most the was M2 - s h ol treatment only the as o 7% which 75%, for Ly+/My + biphenotypic leukemia, biphenotypic + Ly+/My Te niec o AL i our in AMLL of incidence The . olw up follow ing nrl evu sse and system nervous entral I our In . boml Me5EO AML AMLex5/ETO, abnormal e f hmteay 6 cases 6 chemotherapy, of se biphenotypic are o 5% 3 ae wr ALL were cases 3 50%; for [6] [5 . remission ] [3] and , i lv. But alive. s T ) . Some scholars believe scholars Some . patients e omn clinical common he i 6 n agreement with agreement n e le ae higher age, older re nqe lncl and clinical unique cases css received cases 9 oe report some s is reported is encountered type encountered : , i s css did cases 5 died. eas o no of Because leukemia. 3 ae were cases 3 , n accordance in who cases 3 respectively Fv cases Five . achieved 1% to 1% bone even Now who - n the C), o t - - - , . 523 Downloaded from http://journals.tums.ac.ir/ on Friday, April 27, 2012 524 factors prognostic poor two the are rearrangements gene MLL and chromosome Ph gene. ABL of expression is chromosome the of changes. genetic cases AMLL abnormal many are There located is gene MLL know, we As cases. q22), 21)(q2, t(8, q13), 22)(q44, t(1, inv(16), this in 11 structures abnormal t(9; and 22) t(9; t 11), t(9; 9), t(l; 22), t(9; Structural separately. diploid hyper cases 2 chromosome abnormal were body hy diploid, Sub AMLL. in abnormalities chromosomal cases of 80% to 60% that confirmed childhood cytogene AMLL studied have researches recent more so factor, prognostic independent an as recognized literature. the in reported HLA of cell cases 7 and stem antigen CD34 marker hematopoietic of expression positive expression. lineage of expression highest the were CD10 and CD19 phenotype. immune myeloid of expression highest 14 In cases. in biphenotypic our HLA and expression antigen CD13, and CD33 CD7, CD3, CD2, T/M reported type biclonal (2) marrow; bone in antigen lymphoid and antigen biphenotypic (1) types: three into divided be AMLL. can AMLL lineages, the diagnose to fac principal the recent been has immunophenotyping In ALL. or cytometry, flow AML of application wide the with years, as misdiagnosed be to patients our age of re ot, which ports, e dpod pril rsm ad h monomer the and trisomy partial diploid, per Cytogene illegible, mostly was AMLL of morphology The css ad T+B and cases, 2 series in [11] 3, - - had R which DR, 18 DR were also expressed also were DR Fr th For . and were all pairs o pairs all were hoooe tutrs asn MLL causing structures chromosome tic AMLL cases of AMLL, with AMLL, of cases boml chromosome abnormal in (3) ; T/B type s changes of childhood le childhood of changes t , c i 8 cases, T cases, 8 c ud be ould In addition, the emergence of Ph of emergence the addition, In on t affect to bound with . characteristics in te xrsin f myeloid of expression the : cases, CD13 and CD14 and CD13 cases, hge poaiiy f Ph of probability higher e hl ery antigen early while Of bilineal - 1 case. 1 y/y biphenotypic Ly+/My+ ) is chromosome h 1 css 2 cases 2 cases, 14 the are e (5 i each in (15) del (6; 14), t(8; 21), inv(16) 21), t(8; 14), (6; eas of because osset with consistent f phenotype f - codn t different to According Ly+/My+ biphenotypic Ly+/My+ series CyCD22, CD10, CD19, CD10, CyCD22, oe common more type [ B/M . The children in children The . 10] [8] a t had s had were t (9; 22), (9; t were . In this In . . h abnormal the . The majority The . abnormalities h younger the Lee numbers in ukemia B had expression he s o - Ly+/My+ 14 cases, 14 n 11q23. n f CD34 of had highest t al et cloned 11q23 series The . those in in had one are the tor as [9] B 4 3 , , Zheng CR; treatme of course first cases 5 and cases 4 AMLL, article, this In significantly. period same the at (82%) (62%) ALL and AML of rate CR the than lower were both Legrand while 16.67%, was and outcomes. various with AMLL of treatment rearrangements. AML AMLex5/ETO, were results positive the and cases, 5 in detected In found. been not have abnormalities genetic and chromosomes in AMLL of biomarkers the But AMLL. of prognosis poorer the explain also could genetics molecular and cytogenesis AMLL, in MLL and chromosome hospital. our in Committee Ethics Institutional the and labs, of Technology University and Science Huazhong College, Medical Tongji Hospital, Hem Tongji of laboratory Pediatric Clinical and Group the and of doctors all nurses to gratitude and thanks sincere my show to opportunity this take to like would I Acknowledgment and collaborate should views. their exchange researchers more that necessary is it AMLL, of treatment and and diagnosis prevention for basis of treatment a provide study the AMLL, of treatment and diagnosis A Conclusion follow and no T of numbers relate e l he tog tee ee ay usin i the in questions many were there lthough t rsn, ay tde have studies many present, At R ae a 6.7, hc was which 66.67%, was rate CR Armstrong Mixed Acute of Study Clinical mtto o te td is study the of imitation d ′ s [14] to younger to 9 cases have received the treatment of treatment the received have cases 9 eot 7%. h rao may reason The (75%). report observed received - AMLL up [12] were u patients our . eotd ht R ae f A of rate CR that reported g f the of age - ETO n children. in ALL cases nt, 6 patients have achieved have patients 6 nt, ie the given for collaboration with our with collaboration for - oiie n ML gene MLL and positive - chemotherapy. lineage Leukemia lineage during this short time. short this during ′ s fso gene fusion , [13] patients, and patients, little tlg Working atology eie of regimen o mrv the improve To a 4.% and 47.0% was these results of results these eotd the reported ae number case oe than lower ; Y After the After Zhang were s Faber fewer ANLL MLL , et al ,et be Downloaded from http://journals.tums.ac.ir/ on Friday, April 27, 2012 Refe of Conflict Iran J Pediatr; Vol 2 Vol IranJPediatr; 6 5 4 3 2 1 ...... rences hlrn te xeine f t ue Children’s Jude St Hospital Research of experience in the leukemia children: lineage mixed Acute SC. Raimondi 2009;94 strang lineage: mixed Biphenotypic MC. Béné lymphoblastic Haematologica population acute Chinese a of series case and a leukemia: leukemia myeloid acute of that with comparison in leukemia acute SQ, a Lü of characteristics M, biological Wang XQ, Xu leukemia 2009 with acute children of biphenotypic outcome and characteristics Al 185 adults two in (6 t a and leukemia lineage mixed CA, Griffina R, Yonescua M, Georgya leukemia 1997;82 biphenotypic acute MatutesE,Moril - Seraihy AS, Owaidah TM, Ayas M, Ayas TM, Owaidah AS, Seraihy (1) ; I 94 nterest: :28 (7) (12) (1) 1 - (No 31. :891 : 64 : 1682 4 ); . - 2009 - 6. None l Dec 3. a R, Farahat N Farahat R, a acr Genet . - Blood 90. 20 ;94 e . e 11 (7) , 2009 bilineal :919 t al. et ; ; 113 , al. et ut biphenotypic dult - . . 27. Cytogen abgos or ambiguous , ; 14 ; Haematologica Haematologica Haematologica (21) lncl and Clinical al et Definitionof ) (q25 ) t al. et :5083 et . Clinical ; q32 ; 2008 Acute - 9. ) ; . 12 11 10 14 13 9 8 7 ...... translocations and a leukemia stem cell program. cell stem leukemia a and translocations SA. Armstrong J, Faber 81. leukemia. lineage RK. Slany C, Bach signatures. Genomics specific lineage and lymphoblastic acute pediatric in rearrangements Dell'Orto A, Zangrando subtype. Assoc aggressive an be not may single a leukemia myeloid in acute biphenotypic AC. institution: leukemia myeloid Feng acute of TD, analysis Tan MY, Lee Cancer Entity. Clinical distinct a constitute leukemia CD10 and M, leukemia Konig lineage G, Mann A, Attarbaschi ra outcome a leukemia: bilineal Ansari EG, Weir ramn fr ihntpc ct leuke acute biphenotypic Haematologica, for treatment C Zheng HaematolJ Br P and cytogenetics whi prognosis poor with entity an leukemia: acute biphenotypic Legrand ResCancer ylbatc ekma ML pcfc and specific MLL leukemia: myeloblastic 2007;70(7):269 Res , . O Leukemia u J Wu 2009 - , 2006 2007 eaie pre negative ert JY Perrot 1998 , ; 2 h s eae t unfavorable to related is ch 2009; i X Liu ; ;67(18):8425 - :36. 12 ai A Btsa D, Batista MA, Lari Molecular pathology of mixed of pathology Molecular - uue Onco Future ; - (10) 2007 100 lcpoen overexpression glycoprotein eragd hlho pro childhood rearranged , 94(12):1778 - 73. , t al et MC, Kronnie G, Kronnie MC, (1):147 :2988 ioi G Simonin - ; ie lnae leukemia lineage Mixed 21 aue lymphoblastic acute B poor with disease re . (11) Wha - - 94. 8. l - 55. Clinicopathologic : 2009 2264 i te optimal the is t - M Medical BMC 80. e al. et , t al. et t al. et ; Ci Med Chin J - 5 70. et al et (8):1271 Mixed Acute . Adult mi MLL Clin - a? B - - . 525