Document k6Vro9p3n5QEpwko0o6j6xLZn

Risk of acute myeloid leukaemia and multiple in workers exposed 10 benzene 3 c,, .q -7 /I i` .-_--..- - ....??%A.-. 381 stem cdls in leulraemogenesishas been inws- t i g a d . Smn crlls can bt classifid inb? two major megories: &e pluripordd stem cells, which ace resposihle Tor rhe productitin. of circulating elQ0enr.s; and heir dircct dcsccn: dam, rhe c o d u e d piecursor cells, which a m prograrnrncd to fdkw a single line c t f M- fcrcnriiidon. Both m vivo and in V~UQ srudics have hdkared char &e committed stem bre- hrr?imor pcMmiior) crlls ast capabk d self mcwd and mpliflcahn. Inthe posr, ~tpi:ml pmpo*d hypotheses hsve suggested rhlr che cfkcts of bcnzcnc rnctaholites on s t r m c d k have a major impacr on cell pmliindon and diffmtiation during rhr u r l y a w s of Icnkacmogcncsis.In most of thcse hypothcxs b d e or no discinccjan was made b e m a rhr pluriporcntisl and tbc commitrcd s m cclk. Recem research has indicamd dmr Ihc com- mirred s t e m cells or progaitor cdIs p1,y 10 important part not only in the mamtenancr*of nomal, soxdy smo;:hacmopoiesis but also in drr artialagy ofcell r y p rpec3.c leukaeniins. B a d on an invcsriguticm of imnsurm- globulin =ne organisadon and cxprcssiori in hscfiapoietic stem cell ledenria, Fard PI ut hwe shown that a dona1m t leading to blast crisis can occur in a cmmniaed B ccll ptccur- soc rarha than in thc pluripotrntid iten%cell Based on human DNA ulaly:rcs, Mahcr CL a?ccmciudcd char CLMLadd ClL do not arisc from a common progenitor and that these rnalgxm5es arise &om two distinct prrcuMrJ.'* Laboratory invcatigations of the c&cts of benzene m d in merabolb on stem and proga%torcs!l rcguktjon by h r u et d have offered a mcchanirdc -lanation for the sdenive increase in AMLI7 The i n v t d p - aons have shown &at -ne in vjvo imd hyhquinonc (a bcnzenc mmbolih) in vitm plrat chc recruitment or &ula&o of myeloid progenitor cells, &-by increasing the number of cells at risk of dcvcli*phg kakacmia. Furrhcmarr, vbcse invcstigadsns haw indicated that this cffccr is s c l ~ 5 . feor mxuicmear of myeloid cells &at respond IOJ specific myeloid growth factor, GM-CSF. This eEect, on tbe orher hand, is not h i n d For oehrr facmrs a-chted ai& rcauitmcnt or stimulnrion of lympb&d ~ r o p - minx 4 s . Thus, recent advances h orher dbdphcs confpm the qmicmiologacalobsemauon that ltuhemii is a group of disdnct malignancies rhpr shallid be analped scpwaocly. As corn- mmtcd prcriwsly,'"" very few i d t i d u l l studies have estimates of exposure to buw:nc sad cari provide cnougb caws far leukaemia cell m e specific anatgis. In term of MU. the possible exception k h r Pliofilm S K U ~ YIn h a c , I present sn m d y s i s specire to .WvlL based on tbc Pliofilm study, urhich s h i m rhu such a specific analysis proddcs more nppropciate estimates borh for a rhrcshdd and for risk ratios show the thrrskold &an analyses h s c d on all Icukacmia c d l ma combined Also, J prcsenr an analy+. far multiple myeloms by curnularive ~ P O S U Rto benzene. -- .I.I.+.. I ... - i and Georgia).': These rPrdics 5 u p p ~ mthe anaiysis in m y tcpmr. Bcforc closing, ir should be pomied our thar &e number of dcahs from AMI. nr rnul- ripk m4rlorna included in my analyses wps d.and therefore &e results should be hterprcced wirh caution md in conjunction with studies drcady mationed. Ncvtrrh&ss, pnViou8 analyses bared on che same yt of dau have k c n rdicd upon by scvcral regulatorp agencies for policy rnPhng These regula- Wry piiciCs should be r e - d c d m vit?naf ttrc n m analpcs for A M L and atulriplc myeloma presented in this rcport. Condusiom 73rer: decadrr ago, Hill sct hrth crjrcria for asscssmcnt of csusatian." The s a m e mrcria were used in evaluadag cancer nslu rclxtcd to ~ t h c t ain the Swan G m a l ' s rcpoit 00 smoking,Q iiud by chc Iorernarionai r+nry for b e a r c h un Gang= in eva1uatio.n of carcinogeniciv.'' Specificity is one of rhe majqr criteria rOF cwszcion anrlysi?. Thc analysis sp&c m AML presenrad r ~ l rhis cecporr shows the imperwncr d ?Acing?pa- fdty into cnnsidmtion. M a u s annl.wcs b e d on d Ieukaemra c t l cppe corikined have incorredy set &e esimvrcrd thrrshold mo luw bur undrrrstim3rrd.risk 3bOW h e threshoid. T h e rsdmared rhnshold spediic to AML was found m be at Iew 200 ppni-:tears byred un one set of exposure cstimarts; and much higher, had orher nposure earmiam (morr likely m m accurate) & e m used. Cumnt rcgulorory polides relying on previ- ous andyis based on dl leukaemia eel1 rypa -hind should bc nxxamincd. TX anS11gsi.s on mulupk mpetoma stwan *ax no si& cp~llincrease was found, md thwt no cxpo- --T+mnsc relation b m c n cxposwure to bcrmne and multiple mydoma was derccrrd. These results pre cansistcnt with findings from nthrr cpidcmiologicnlstudies. .--- .2 -- ! Correspondence and editofis - .. - .- -.. ... ...:.+.! - ..*.. .r.*.. ,. A.- ..