Document qk2xQ1XvRnLV0qYrXX4JrQjVE

Chromosome Studies in a Case of Benzme-Induced Erythroleukaemia* ALESS.LYDRI FORSI and L. LIOREO Clinica ale1 Lauoro '* L. Druoto", L*nicrrnty cf .iliim, .\fiim, IrOry CASE REPORT S.Y., female,aqe 37. Xothinq important in the family hitory. One normal pmpancy at the age of 29. one slantancan abortion at the ape of 31. T h e patient had been working from 1959 to 1966 in a small factory of bepugowr;rhe usually worked at packing, but she was a b often enqagcd in the mounting of the C ~ K S with 8 glue containing l a t a and para rubber, which was diluted with benzene and applied directly on the lining with a finger. The wholc ptocminq of the beauty c a s a waa a n i e d out by 4 5 persons in a smail mom. T h e patient reported that, apeciaUv during winter, there waa a m ~ n agmell of benzene in the room. Since 1965 the patient had suffered from frequent m c u o w In JuIV 1966 the patient started complaining d w u k n a s , anomia. pallor, irmgular fever (up to W C ) . In Augurt 1966. following a #ym meawrtugia,the patient waa admined to a g y n z m o l ~ c department to have a cumtcage and, due to the finding ofanacmk, she WIU truucemdto the Clinica del Lavoro on I Scptuaber 1966. At . d m k i o n the blood findinp were: Hgb 8 g/lW ml, RBC 3,000,000/mm3, WBC 4500/mmJ with ncutrophih 38%, eosinophih ,?:! lymphocyta 1404, mwa 6%. metamyeloqto 1% mydocyta 2604. buophilic Submitted for publication I 1 April 1969. Acecpted 14 May 1969. *% invatiqation was supported in whole by Public Health Scrvice Rucarch Grant No. UI-00465 from the Sational G n t a for Urban and Industrial Health. readmitted in emerqency due to mere mctrorrhaqia, thrombopblcbirir of the left leq, hiqh fever. The blood findinqs were: Hqb 6 . 1 e'100 mi. RBC O,ooO.OOO!mm', WBC 30,000!mma with neutrophds be's. lymphocvta 4 9 ~ .meramvelccvus 19O;, mvclocvta 2 O , , mveloblasu lye, h3cmoqtoblasa 5'%, ; audophilic m z h r o b h o IS. polichromatophdic cr)rthmblasrt 7 , bwphilic e+ b l u u 1, prccrvrhroblasu I . IW \\'BC. Some oi the immature elemmu of the ervthrord ria were P.4S pmitive. T h e leucocyte alkaline phosphatase wore was high (262). At this time a direct chromosome prcpua- tion of peripheral blood was madc From 22 October-1 Sovembcr 1966 the patient was given a .hwc cotme of 6-mmptopunnc 12.5 mqjkgl day), t o p h e r with corricoluroib d transfusions. T h e patient had a partial dinicai and hacmatologd rcmisioo and w1s kept under check for a while. On 23 December 1966 a new bone m w w m p k WI obtained, on which q t o q a e t i c studia were pcrfonnca The panm was similar to that prrviowry daaibal, but tltc bizarre and +at elementr were more numaour T h e mycloid-crvrhroid ratio w i ~0.46. Out of IO00 imcnarurr cell, of bob stria. 2 mima d the myeioid and 6 of the erythroid p m u n ~ nwere found. In the next month the patient became incrrariagly ill, had high i& f m , complained of w e r e joint piim. and praented subcutu~ola and submucous h.rmOrrhqa and liver and spicen enlarganmt T h e patient died on 16 Febntlvy 1967. T h e autopsy findings were: bmchopneumonh. diffuw rubcutaneou and submucous haernorrh;lqa, liver and spleen enlarge- 459 ; ., , . '1 * I. . 8.'-.-1. .- 460 dlrcsandra Farni and L. .Vmm TabL 1. Chromosome count^ in direr! prepmaiumr of pmpheral blood and bow mmmw Date swrcc 14 Oct. 1966 Blood 23 Dec. 1966 Bone marrow . ~mouunccouno <43 44 45 46. 57 335 6 2141 Toul sur- ctflr 73 tetraploid counted ~~ 2 15 ~~~ 13 29 *PseudodlpIoidcuk wth 2 d e n . m t due to m v e mfiltrauoo with aychrold and myclod elemmo. MATCKW, AND METHODS T h e chromosome studies were performed on ...-. ..--- . _- .olrcci prepalatiuiis ui p r i i p k r d Liuuci an; LA-- _.IC _. TL- ".>. * . r r r..,.---L"---rI LIIPi -_-I- .. .A , ... --.--I L L .3.. UlIbLLU .- __--._1 - - ...._.C_ r--- ? .-- 1 1.. 1. .**..L1 y.... C-..4 -_.--- ---h--e.t .". . i -oA (3:I ), and chromosome prcparatiom were made by the a x - d q i n r : method. wth slqht d,tcrmined according to Kaplow's y o chemical score [IO]. RESULTS The direct prcparabon of peripheral b l c d was performed at a time when the patient had k e n treated onlv with corticosteroids and transfusions. T h e chromosome studv of the bone marrow was made 1i month after a short course of 6 r n e r c a p t o p u ~ e ;unfortunatelv no chromosome stuchcs had been performed at the m e of the fmt bone marrow biopsy in September 1966. The results of the chromosome counts art summanzed in Table 1. Complete chromosome analysu was performed on 11 metaphases from the penphcral blood [Table 9) and on !? meraphases trom the bone marrow 'Table 3' Both simples were charactenzed by a stm- line ~ l t ahchromosnrnr niirnhrr nf 46, hirt W+ a pscuaodiploid pattern. Tn all pzeudodiDlold mctaohaxs 2 chromosorncs of the E ~ T O L G [l7-18! were m s i n g and 2 marker chrome cnmm were nrrwnt ' F I ~1 and 21 T h e . -. -.L-1- JLCA.*-U-C. *aa ~ ~ C ~ U UTUl, C rndr I nldr 2 dccoralfiz to ice ure or m e Ctucaeo comerencc I i 11. Marker I was a smaii ring chromosome. appeanng most or the urn= cbvlclcd into the chromarids ,Figs. 1 and 2'. Marker 2 was a m n u t e trapment, whose centromere was cw- dent onlv I E ~some metaphases. Both marlien were quite r c c o p z a b l c and were observed also in some other metaphases which were noc nutable for counune. The markers, and cpeaallv marker 1, occupied prdercnuallv a pcnpherai poution in the metaphase spreads (Fiq. 1 and 2). hs shown in Table 1 quite a few rnetaphasa were near-tetraploid ;in these celIs each marLcr was gcnerallv represented m c e or mom (Tables 2 and 3). In some of the best metaphases a Bp- chromosome was also somewhat cnldent; thls chromosome was intermediate between c h e mosomes of pa= 3 and chromosome 4 !Fig 1 and 2 . However, due to the quaiitv of man' metaphase spreads, it 1s difficult to s t m whether this chromosome abnormality WY conslstent. T a b k 2. Chromosorm d - v m r of 11 m e t a p b f r o m Bmt prepmaswon ofpmpiural blood N a d a l h chNo. of A B C D E F Gwlmu2 (17-18) 1 44 - 1 -2 1 44 - 1 - 2 -1 1 43 -1 -1 -1 1 45 -1 - 2 1 45 -2 5 46 -2 1 86. - I - 9 -.I -2 1 I1 11 I1 I 11 43 *In the nur-tetraplod mctaphrra rowng and atra-zhnxnaoma arc r d e m d to h e tetraploid karyotype. (2 r. Chromosome Studits in a Cart of Bm;nclnduccd E~rhroicukarmlo Tobit 3. Chomosomc anairns of I2 mtabkces-from direct prrparolton of bone marrow No.o i so. of chromo- cch soma --~ 1 45 1 45 AB C DE 17-18 -1 - 2 -2 1 46 I 46 5 46 -2 1 57 4-1 +4 +l I 87' -2 -5 I 93. -3 ~~ ~ *See note below Table 2 F G m a r 1 mu:! + I +I -2 11 I 1 11 I1 2I 22 13 DISCUSSION The capa .ity of benzene to induce leukacT i s is we;i known (12, 131. -Us0 cases of acute cnihrolcvk cmia due to benzene are repo:.ted the illness started after 7 also in the same case the almost constant presence of a small acentric fragment in the metaphases with the marker ring chromosome. In our case the minute chromosome seemed actually to be centric. ikming orp;ans were alreadv present. For this ;cmn we can assume that this case of erythro- icukaemja :/as induced by benzene. group suggests however a loss of qcile~':i material, even though a translocation 0; par of d in the acute trans- chromosome patterns STC different from case to case. In the prcsent case, consistent structural chromosome abnormalities were demonitrated in all m e t a p h m , both in the sample of peripheral blood taken before anablastic treatment and in the sample of bone marrow of 2 chromosomes 117-181 was a constant feature of the stem-line of the case d ~ b e d , m e n though in occasional hypodiploid cclh only one J!? chromosome was miaing togetha with chromasoma of other groups. to bclong to the neoplastic stem-Line. In two casu of acute erythroleukaunia rrported in the literature a ring chromosome wiu observed [2, 61. In the case of Di Grado .- rf d [2] the ring chromosome was the size of T h e tetraploid or near-tetraploid metaphases found in the direct preparation both of peripheral blood and of bone marrow qrcseat probably mi- of the abnormal giant el* ments, often binudeated, which were prucnt in Cue of Krogh J e w n [6]. This author reports made at the h e of the chromosome prrparr- '. . .- a.I' ,- .I . 4 a- .. ,, . .. ..,*I; p;; *,.*:.: I; ;2t, : :'.t .,:'.':,'*. I .y.4 -+ . *. ' ',. .i , :.i. ( . 3. : !a A:.& . . .~ . i .. I -cc*% 462 Aiumndra Furni and L. .\fore0 tion mitoses both of the erythroid and of the mydoid series were present, the abnormal mctaphases observed seem to belong to both series. This fact, observed in acute Ieukaemias ais0 by Kroqh Jemen 16, 20, 211, seem to demonstrate that the abnormal cells derive from a common stem-ctll with anomalous chromosome pattern. Regarding the formation of the abnormal complement, it is noteworthy that some of the reponed patients with acute leukaemia or erythrolcukaemia had a history of exposure to S-ra!-s [ I , SJ. The patient with erythm- leukaemia observed by us had been for some ycan exposed to benzene during her work. Benzene exposure is known to be ab]? produce chromosome c h a n e a simiIar to tho%. induced bv X-rays, both in 1)rnphoc)m in bone marrow cclls [22-26.1 The hypothc.;, can thercfore be suggc& that in our cay WTZ-, nht have induced stem-cd chromosome chanea iprobablv brrnt vape-of c h m o s o r n e s of the c group), .I!:< t m o n s e-men1 mlqht ha:, -resulted in a cell with a p s e oumplrr. ment, which gave rise to the abnormal clonr The leiikaemic process might have her:! initiated bv the proliferation of such clone ail,] by its ditTerentiarron into cells both of ulr erythroid and of the mveloid series. 4 RESUME On a itudii Ies chromosomes d'un w d'i@hroleucimu aiguc une m& qui avd Lti exposh au bm;m. A l'rxamen direct tan# du sang que de la modle ossme. iiy avuit une iignie cellulaire CMCC 46 clironwsonaes, Oljcc un ca?o!vpc pstudodipioiak par absence de deux rhmnosoma & .<roup E CL f i c s m e dr deux chromosomrs marqururs !un chronwsawu en anncau rt BE petit f r a p e n t centnpe). Lc caTo!rpe a m a l parausatt itre conynun aux d a x series, puirgue 1 ~cshromosomes marprurs itairnt prrsntis dam touks lu mitasc etudiirs et appartmaient p r o b a b h m f tmt Ci la sine iylhroblastiyue qu'a La sirir. mriloide. Ls auteurs imcttent l'hjpothke que i'exposition au bex& pad amir induii du jragmmtutiow et de-s r i m a n p u n t s chromosomigues dam UIV celluic southe p i , m proitfiration, produismt le clone jri5rolnrchniquc a n o d . b 'TMMARY Cytojmic studies were c&d out in r of acute qthroleukatmia, mhich w m e d in a paticnt who had been exposed to bmient. In direct preparatiohs both of pm$herai blood and of bone marrow, a stem-line of 46 chronwsomcs uas prcseni, u& a pseudodiplaid karTogpe, due to the absencr of 2 dwomasonus of group E and to the presence of 2 d l markers (a ring chromosome c J a minute centricfragment!. As tke marks w e pa& in d the mitoses obscnd, most pobab(v beionging boih to the qthroid and to the mJveioidseries, the a b n o d thromosc, 1c c o m p i m t s c m d to characterize a shficrll common to both srrirs. Tk h_vpothcsi~s .wgpted that the exfisure to bnvm might have induced chromosome breakqgcs and remangmvnlr in a stem-celL, and that p:oiifnatim, pf such a b n d elmvnt mgAl hane resuited in the 9lrolnrknnnic c h . m5A;rlMEMFAs5mc Bei r i m &P m't akuter Eg'lvDleukamie, wekchzr dn Einm'rkq mm B e n d muguctzt wm,unua'en die Chontosm.m untermcht. Sowohl in dcr d i r e k h PrcTpmohbn a h str6menden 3lt~te.saLs a u h in dn du Knochmmarkr war tin <eLLtMn mir 46 Chnnnosomm Omhandcn. Durch die Abwrsenheit von 2 Chromosomm ah Cmpp E und a h Vorhandnrrcinwn 2 klrinm Mar+erchromosomen (ein Ringchromosom und rin k l k ZmtriCches F r a m ) mfrtand &ne ps-udodjpioides Bild. Da die .\larkcrchromasonm bei a i h beobachtetol Mitom vorhando waren, wek-he omutlich sowohl der m_tcloischm ab w h der eyrboblartischen Sctic urgehen, sclvint der pathoiogisck Clrr0marr;nm- bcriond b&&n Senin MzugehiTren. Die Autoren kommen a der &othetkden F o l g m n f , dai3 rs durch die tt'ilkwq du B ~ o ;uh cinem B m h und riner It'iederanardnunq der Chromosomen in einrr Stmnnqelle gdommm war, wobei die Prolifcratinn diem <e& <UT Bildung etnes anomalnr Klow fdlrtc. REFERENCES 1. .4. G . BMKIE,P.JACOBS, J. A. hfCBRlDE and I. hf. TOUGH,Cytogenetic itudia in acute leukaemia. Brit. med. 3. i,1564 (1961). .- ^ * -.. C .:- '.I 7 t.( 1 -A? p;-. .< , .., -.I;; ,- .!. 5'::;.. '.'.i . . L .:.. .' - .- . ,;.; 1 -' 'y-'; "{. .,+'.,-.$:...: ::;: ' 8 . : .~ &+:q.& .; 9:.. .:+ \ ... c '.. _ .I I .. - - .P.. I I Chromosome Studies in a Case of ~~~~~~~Znducrd Eg&rolnrkaemia 2. F. DI GRADOF, . T. ~ I E X D E aSnd E. SCHROEDER, Rinq chromosome in a case of Di Cuqiielrno svndrome. Lonctf ii, 1?43 ;i964). 3. C. \%'.HEATH and it'. C. ~ I O L O X E Y , Cvtoeenctic observations in a ciuc of erythrcmic myelosis. Cnnirr ( P h h d . ) 18, 1 i 9 3 : 1965). 4. K.A. kossoc~oc1, %J'.. \ h r s and i v . D.LUTSHECKh,romosomal aberrations in acute leukaemia. Blood 26,610 (1963). 5. N. RICCI,Xnomalia cromorornica in un c ; w di aindromc eritroleucemica. Progrrsso mid. (.\hpoli) 21, 309 (1965). 6. M. KROCHJESSEN, Chromosomal findinqs in two cases of acute erythro- leukaemia. . i c h mcd. rcand. 180, 245 (1966). 7. E. ESGEL,L. C. ~ I C K EaEnd K. i V , BU.WNG,Chromoxoma 17-18 in leukae- m i a . Lnncef ii, 42 ( 1967'. 8. R. V. SMALLEYand B. S. BOUROXCE, Hyperdiploidy in a patient with Di Gugliclmo's syndrome. .Arch. i n f . .\fed. 120, 399 ' 1367). 9. G. CASTOLDIL,. T. YAY, \I*J. .M-rcs and W. H. CROSBYC. hromosomal studies in cr).throleukcmia and chronic cryrhremic myelosis. Bfood 31, 202 ( 1968). 10. L. S. %FLG-.~-, .\ k k : x ! x ~ : c ~ ! F r z d u r e for localizing and evaluatinq leucocyte alkaline phosphatase activity in smears of blood and bone marrow. RIMA 10: 1023 (i933'l. 11. Chicago Conference: Standardization in ~ U R Ucpt~ugcnrtics. Birth defefu: Original Article Sene Y (2).-1he Nauonai Foundauon-Xuch of Dirna,Sew York 9 14. B.GALAVO-ITaInd F M.TROWE.rythrolr.zacmic myelosis in benzene POLoning. Bnf. J Ind. .Wed. 7, 79 (1950). 15. T. PATERN.S. TEODOaRnId F D o n ) , I .mopaua benzolica: contributo dinico (criuomielopatia anentrermca~e corcc*tr g e n d Pohcl~n~coS,a. p r a t 61, 905 11954). 16. C. W.HEATH and J. Y. Beuhxn, C y t o p e u c findingsin aythrrrmc myelom (Abstract). Blood 26, 874 (1965). 17. A. S.D. SPIERS and A. G. BMKIEC, ytogeneuc evolution and clonal prolifemuon in acute traruformation of chronic granuloc).trc leukaemia. Bnt. J . Cancer 22, 192 (1968). 18. A. A. SANDBERTG., ISHUURAY, . KIKUWan8 L. H. CRO~WIXITCZh,romw s o d differcnca among the acute leukcmiar. Arm. N.T. Acad. SR. 113, 663 19. (1964). E.EvceL, L.c. M cG r an lomiqua dam la maladies dmSalfi.qEnNuGdCuLsa-DnMgE.OLKinN. OmLiLd~.P-CTM,.4Obdcorr9.a7-U,9o-n0-s1.ch(.1r.9o6m-1B-) . 20. M. K R ~ C HJEWEN and s. A. KILLMN~N,Chromosome studia in acute le&- d.Evidence for chromosomal abnormalitia common to crythroblasuand leukaemic white cells. A r b mrd. s c d . 181, 47 (1967). 21. M.KRWH JEWEN. Chromosome studies in potentially lelllarmic myeloid disorders. Acto mcd. s c a d . 183,535 (1968). 22. G. POLLINIand R. COLOMB1I1, danno cromommico midollan ncll'anemia 8phStiCa bcnsOhCa. hf8d. d. h!%, 241 (1%) 25. G. POLLIXand R. Co~orrsr,I1 danno c m m d c o dei linfodti nell'emoptk benzcnica M d . d. h r o 55, 641 (1%). 24. I. M. TOUGH and W. M. COL=TBROW, Chromosomeaberrationsand aponvc to ambient benzene. h c t i,684 (1965). 25. k Forwr, Chromosome changu due to chronic aposurf to benzene. Proc. XV In&.C w . Occutd. He&, Vienna, 1966. Wiener Meduinische Akadunic Vol. II/I, p i . 437-439 (1966). 26. A. Foam and L.MOREOC, vtogenetic studies in a case of benzene l e u k a d E*. 3. C- 3,251 (1967).