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Isochromosome 14q in chronic myelomonocytic leukemia
Isochromosome 14q in Chronic Myelomonocytic Leukemia
Meloni-Bailliet et al. I11 publishe(I flu'ee cases ol a(:uI, n(mlymphc)(:yli(: leukemia (ANLL) with t r i s o m v 14 as the sole (:llrom()s(..e al)normality, and s u , ~ e s t e d th.t su~:h a(] a b n o r n l a l i t v , either as a l l (,~Xtl'~l ( h r o l ] l O S O l l / e OF Sill i s o ( ; h r ( H l l ( ) S ( H l l e , (',OH I(I I'(~t)lefi(,Hit a n e w (:ytogeaeti(: enlitv w i t h i n ANIJ.. We report herein . ps~tient with uhr(miu myelom(mo(:yti¢: l e u k e m i a (CMMoI3 in w h i c h the (:ylogeneti(: siu(Iv (lisclos.d an isoul~romos(mm 14( I in a d d i t i o n to the h~ss (fl the Y (:hr(mlos(m/e. A 77-year-old male was referred to our hospital because of lewd,r, anemi(; s y n d r o m e , and a r n a c u l o p a p u l a r skin rash i n v o l v i n g thorax, a b d o m e n , and l o w e r extremities. At a d m i s s i o n , the h e m o g l o b i n (Hb) v a l u e was 5.6 F,/dL, hemato(:riI 17(;', M C V ~V fI., w h i t e blood cell (WBC) (:ount 3.6 :x: 10'/L, w i t h 27% n e u t r o p h i l s , 1'",,. e o s i n o p h i l s . 58% l y m p h o c y t e s , an(114% mono(:ytes. T h e t)latelet (:ou nt v,,as 42 x 10"/L. T h e HamDacie and sucrose tests w e r e negative. S e r u m ferritin levels w e r e of 922 ng/ml, and l e u c o c y t e a l k a l i n e p h o s p h a t a s e score was 100 (normal range: 20 401. The b(mc marn)w was hyper(:ellular w i t h (lyshem(q)()ittli(: fr, att~res, mainly afle(:lill~ the ervthr(d(I imd megakaryo(:yti(: series, witlmul blast (:ells. l'erls stain sh()w¢~(t im:r~ased mac:r()t)hagi(: iron with 28",,~, si(ler(d)lasts [)ill with(ml ringed [()FillS. []lille Illilrl'oW biops~ s h o w e d hyper(:elhflarity, (lyshem(q)(deti(; features, sis well as (tiftuse reti(:ulin fibrosis. T h e biopsy of skin lesions s h o w e d a dermal and hyl.,(h~rmal intiltrati(.i by ilnmattlre (:ells ()f m(m(~(:vti(: al)t)eal-anue. Nat)hlh(d-ASl)-a(:elate esterase stain was l)ositive, this rea(:tion bein~ inldlfite(t bv s o d i u m fluoride. The imnuln¢)¢:vt.(:hemi(:al stu(ty (immunot)h(~st)llatase meth(,(t) dist:h~se(t t)ositivitv ()t m(..~(:vt i(: u.lls t ( . m . . ( ) (:lonal antibo(ties (]DI4 and (;I)33. T h e patient o n l y r e c e i v e d supl~ortive therat)y w i t h pa(:ked red bh)od (:ells. Three m o n t h s after the a d m i s s i o n , the n u m b e r of skin lesions in(:reased and the i)eril)heral bh~od s t u d y revealed: Hb 6.2 g/alL, hemato(:rit 20%, and WBC (:oun! 20 x 10"/I. with an a b s o l u t e m o n o c v t e ( : o u n t of 16 x 10"/L. A s e ( : o n d b o n e m a r r o w aspirate s h o w e d dyshelnopoieti(: features, i n c r e a s e d n u m b e r of mono(:ytes and l)romono(:ytes, as well as 8% blast (:ells. Diagnosis (fi ( ] M M o L a(:(:or(ling t(~ the trAB ¢:riterisi [2[ was eslablishe(t. The, bone m a r r o w (:yt()geneti(: SiLl(h: (sh()rl teI'iII (:ulture without stimnlati()n) r e v e a l e d a loss of the Y (;hrolnosome in a(t(lition t(i an is()(:hr()m()s()me 14( 1. The t)erit)lmral bh)od (:yt()~ene, ti(: stLl(h' (72 h()tH's (:ulture w i l h i)hytohema,u,~lutinill) was normal. The patient received ($-mer(:al)tOl)Urine (50 mg/(lay), but re|use(I stfl)se(lu(~nt therat)y and die(I tw() months after the (tia~nosis of (]MNhd~. The patient rel)orted herein was (lia~nosed as having CMMol~ be(:ause of m()no(;ytosis in ad(lition to dyshem()poieti(: fealures and an increase ()f m()n()(:vti(: t)re(:ur sors in the bone m a r r o w [2]. ()nlv 8% blast (:ells were seen sit (tiagn()sis. ,'-;kin infiltration, althou,qh infr(;(lue, nI in myelodysplasti(: s3 n(h'omes (MI)S), can I)e (d)serve(I in (]MMoL, either at diagnosis or w h e n the disease e ~ o l v . s to a(:ut~ l e u k e m i a [3]. The most o u t s t a n d i n g feature in this patient was the (:yt~),4eneti(: stu(tv, whi(:h revealed. in a(htition to the loss of the Y ( : h r o m o s ( . n e [4]. an iso(:hrom()s()me 14( t. T h i s fin(ling has been p r e v i o u s l y r e p o r t e d in some hematoh)gi(: disorders [5]. n a m e l y ANLL [1] and myeloproliferative syndromes [1,6], but. to our knowledge, has not been reported in MDS. In addition, isochromosome 14q has not been recognized by the MIC group
1 39 I ( l ! t g l I':IsI~viI~I" ':'l:ilu~:(t P u t ) l i s h i n ? C(I., I n ( . (j~)r) AV(tllll(t O] t[/(! ,'\lll(!l"i(:aS, N(tw Y t l r k . NY h i { I l l )
(](lIl(:ltI" ('J(!lll!l (:VIO:AI!IHtt 5221 ~!) l']() l l g ! ) l j () 1(15- t(i((l~ !11 ${13.51(
140
1. bd. Riberu et ~tl. a m o n g t h e (:ytogeneti(: a b n o r m a l i t i e s in MDS. e i t h e r p r i m a r y or se(:on(tary [7}. It is of n o t e that all i s o c h r o l n o s o m e 14 h a s b e e n o b s e r v e d in cases of P h i l a ( l e l p h i a (:hrotnos o m e n e g a t i v e c h r o n i c n r v e l o g e n o u s l e u k e m i a , a n d it h a s b e e n s u g g e s t e d that sut:h a h e m o l ) u t h y is simih+r t() (2vl:'vh)l, iSl. eSl)e(:iallY w h e n t h e b(:r,'obl rearrmt~,ement is m)t present. T h e i l l c r e a s i n g frequen(:y o[ trisollly 14 w o u h t suggest t h a t su(:h a (:ytoget]eti(: a b n o r n m l i t y (:ould c o n s t i t u t e a p r i m a r y (:hrom(Jsomal c h a n g e in s o m e henlatologi(: d i s o r d e r s , a l t h o u g h f u r t h e r o b s e r v a t i o t l s are neede(t to e s t a b l i s h d e f i n i t i v e l y its role, in the, p a t h o p h y s i o l o g y of m a l i g m m t (tiseases of blood.
J. M. RIBERA
A. A V E N T I N F. MILL.~ G. LAS HERAS
l ) e p a r t m e n t of H e m a t o l o g y t t o s p i t a l ( ; e r n l a n s T r i a s i Pujol Barcelona, Spain t t o s p i t a l de la S a n t a Creu i S a n t Pau Bar(:elona, S p a i n l ) e p a r t m e n t of H e m a t o l o g y l t o s p i t a l G e r m a n s Trias i Pujol B a r c e l o n a , St)ain
REFERENCES 1. Mdoni-Builliet ,,\, Mor,-,,un R. Forth IL. Kingsh!v I'](], S~mdher,~ AA {I!)fi!}): Trisomv 14: ~Lnew entity will+in a(:tlt(t IlO]| lyn+l)l.)tfl.sti(: hmkemi.. (:unut+r (hme+t (]vlogt+ncl 43:35 3ft. 2. Bennett JM. C~flovsky l), Daniel MT, Flandrin (;, (;-alton I)A(;, (;ralni(:k ttR, Sultan (] (1982): Proposals for the (:lassit'iuatiml of the myelodysplast ic synd rmnes. BrJ Hacmatol 51:18!) 1!)9. 3. Copph+stone JA, Oscier 1)(;. Mufti GJ. Hamblin TJ {19~~61: Monocytiu skin infiltrati~m in chronic myelomonocyti¢: hmkae.mia. Clin l,ab Haematol 8:115 119. 4. (;roupe Fran(:ais (te, Cytogenetiqtm H e m a t o l o g i q u e (1986): (:yto~clmti(:s of (:hrotfi(: myelonl(> nouyti~:leuketnia. Cant:er(](met (]ytogenttt 21:11 3(). 5. Labal de Vinuesa M, Shivutsky 1, Larripa I ( 1987]: I)resent:e ()t isot:hromosomtts in httnlatolo,~i t:al disorders. Cai~t:er (;(;net (]ylogenel 25:47 54. 6, Shashady (;(;, Baumilhtr R(:( 1980): Philadelphia chrolnos(mle negative (:hr.ni. myeh)glm()us leukemia with lrisomy 1). Arch Pathol Lab Med 104:336 378. 7. Third M[(] Cooperative Stu(ly (;l'Otlp {1!}88}: Re(:omnmndalions [or a morphoh)gic, illllntlnologic and (:ytogenetic (MIC} working .lassifi(:ation of the primary and therapy-related my(dodyspUasti(: disorders. (]~ln(:er (;ene, t (]yto~4ent;t 32:1 10. 8. Pugh W(], Person M. Vardiman IW, Rowley II) {1,q85}: Philadelphia t:hromosomc negaliw! chronic myelogenous Icukaemia: a morphologi~:al reassessme, nt, Br I Hacmatol 50:457-457.
Meloni-Bailliet et al. I11 publishe(I flu'ee cases ol a(:uI, n(mlymphc)(:yli(: leukemia (ANLL) with t r i s o m v 14 as the sole (:llrom()s(..e al)normality, and s u , ~ e s t e d th.t su~:h a(] a b n o r n l a l i t v , either as a l l (,~Xtl'~l ( h r o l ] l O S O l l / e OF Sill i s o ( ; h r ( H l l ( ) S ( H l l e , (',OH I(I I'(~t)lefi(,Hit a n e w (:ytogeaeti(: enlitv w i t h i n ANIJ.. We report herein . ps~tient with uhr(miu myelom(mo(:yti¢: l e u k e m i a (CMMoI3 in w h i c h the (:ylogeneti(: siu(Iv (lisclos.d an isoul~romos(mm 14( I in a d d i t i o n to the h~ss (fl the Y (:hr(mlos(m/e. A 77-year-old male was referred to our hospital because of lewd,r, anemi(; s y n d r o m e , and a r n a c u l o p a p u l a r skin rash i n v o l v i n g thorax, a b d o m e n , and l o w e r extremities. At a d m i s s i o n , the h e m o g l o b i n (Hb) v a l u e was 5.6 F,/dL, hemato(:riI 17(;', M C V ~V fI., w h i t e blood cell (WBC) (:ount 3.6 :x: 10'/L, w i t h 27% n e u t r o p h i l s , 1'",,. e o s i n o p h i l s . 58% l y m p h o c y t e s , an(114% mono(:ytes. T h e t)latelet (:ou nt v,,as 42 x 10"/L. T h e HamDacie and sucrose tests w e r e negative. S e r u m ferritin levels w e r e of 922 ng/ml, and l e u c o c y t e a l k a l i n e p h o s p h a t a s e score was 100 (normal range: 20 401. The b(mc marn)w was hyper(:ellular w i t h (lyshem(q)()ittli(: fr, att~res, mainly afle(:lill~ the ervthr(d(I imd megakaryo(:yti(: series, witlmul blast (:ells. l'erls stain sh()w¢~(t im:r~ased mac:r()t)hagi(: iron with 28",,~, si(ler(d)lasts [)ill with(ml ringed [()FillS. []lille Illilrl'oW biops~ s h o w e d hyper(:elhflarity, (lyshem(q)(deti(; features, sis well as (tiftuse reti(:ulin fibrosis. T h e biopsy of skin lesions s h o w e d a dermal and hyl.,(h~rmal intiltrati(.i by ilnmattlre (:ells ()f m(m(~(:vti(: al)t)eal-anue. Nat)hlh(d-ASl)-a(:elate esterase stain was l)ositive, this rea(:tion bein~ inldlfite(t bv s o d i u m fluoride. The imnuln¢)¢:vt.(:hemi(:al stu(ty (immunot)h(~st)llatase meth(,(t) dist:h~se(t t)ositivitv ()t m(..~(:vt i(: u.lls t ( . m . . ( ) (:lonal antibo(ties (]DI4 and (;I)33. T h e patient o n l y r e c e i v e d supl~ortive therat)y w i t h pa(:ked red bh)od (:ells. Three m o n t h s after the a d m i s s i o n , the n u m b e r of skin lesions in(:reased and the i)eril)heral bh~od s t u d y revealed: Hb 6.2 g/alL, hemato(:rit 20%, and WBC (:oun! 20 x 10"/I. with an a b s o l u t e m o n o c v t e ( : o u n t of 16 x 10"/L. A s e ( : o n d b o n e m a r r o w aspirate s h o w e d dyshelnopoieti(: features, i n c r e a s e d n u m b e r of mono(:ytes and l)romono(:ytes, as well as 8% blast (:ells. Diagnosis (fi ( ] M M o L a(:(:or(ling t(~ the trAB ¢:riterisi [2[ was eslablishe(t. The, bone m a r r o w (:yt()geneti(: SiLl(h: (sh()rl teI'iII (:ulture without stimnlati()n) r e v e a l e d a loss of the Y (;hrolnosome in a(t(lition t(i an is()(:hr()m()s()me 14( 1. The t)erit)lmral bh)od (:yt()~ene, ti(: stLl(h' (72 h()tH's (:ulture w i l h i)hytohema,u,~lutinill) was normal. The patient received ($-mer(:al)tOl)Urine (50 mg/(lay), but re|use(I stfl)se(lu(~nt therat)y and die(I tw() months after the (tia~nosis of (]MNhd~. The patient rel)orted herein was (lia~nosed as having CMMol~ be(:ause of m()no(;ytosis in ad(lition to dyshem()poieti(: fealures and an increase ()f m()n()(:vti(: t)re(:ur sors in the bone m a r r o w [2]. ()nlv 8% blast (:ells were seen sit (tiagn()sis. ,'-;kin infiltration, althou,qh infr(;(lue, nI in myelodysplasti(: s3 n(h'omes (MI)S), can I)e (d)serve(I in (]MMoL, either at diagnosis or w h e n the disease e ~ o l v . s to a(:ut~ l e u k e m i a [3]. The most o u t s t a n d i n g feature in this patient was the (:yt~),4eneti(: stu(tv, whi(:h revealed. in a(htition to the loss of the Y ( : h r o m o s ( . n e [4]. an iso(:hrom()s()me 14( t. T h i s fin(ling has been p r e v i o u s l y r e p o r t e d in some hematoh)gi(: disorders [5]. n a m e l y ANLL [1] and myeloproliferative syndromes [1,6], but. to our knowledge, has not been reported in MDS. In addition, isochromosome 14q has not been recognized by the MIC group
1 39 I ( l ! t g l I':IsI~viI~I" ':'l:ilu~:(t P u t ) l i s h i n ? C(I., I n ( . (j~)r) AV(tllll(t O] t[/(! ,'\lll(!l"i(:aS, N(tw Y t l r k . NY h i { I l l )
(](lIl(:ltI" ('J(!lll!l (:VIO:AI!IHtt 5221 ~!) l']() l l g ! ) l j () 1(15- t(i((l~ !11 ${13.51(
140
1. bd. Riberu et ~tl. a m o n g t h e (:ytogeneti(: a b n o r m a l i t i e s in MDS. e i t h e r p r i m a r y or se(:on(tary [7}. It is of n o t e that all i s o c h r o l n o s o m e 14 h a s b e e n o b s e r v e d in cases of P h i l a ( l e l p h i a (:hrotnos o m e n e g a t i v e c h r o n i c n r v e l o g e n o u s l e u k e m i a , a n d it h a s b e e n s u g g e s t e d that sut:h a h e m o l ) u t h y is simih+r t() (2vl:'vh)l, iSl. eSl)e(:iallY w h e n t h e b(:r,'obl rearrmt~,ement is m)t present. T h e i l l c r e a s i n g frequen(:y o[ trisollly 14 w o u h t suggest t h a t su(:h a (:ytoget]eti(: a b n o r n m l i t y (:ould c o n s t i t u t e a p r i m a r y (:hrom(Jsomal c h a n g e in s o m e henlatologi(: d i s o r d e r s , a l t h o u g h f u r t h e r o b s e r v a t i o t l s are neede(t to e s t a b l i s h d e f i n i t i v e l y its role, in the, p a t h o p h y s i o l o g y of m a l i g m m t (tiseases of blood.
J. M. RIBERA
A. A V E N T I N F. MILL.~ G. LAS HERAS
l ) e p a r t m e n t of H e m a t o l o g y t t o s p i t a l ( ; e r n l a n s T r i a s i Pujol Barcelona, Spain t t o s p i t a l de la S a n t a Creu i S a n t Pau Bar(:elona, S p a i n l ) e p a r t m e n t of H e m a t o l o g y l t o s p i t a l G e r m a n s Trias i Pujol B a r c e l o n a , St)ain
REFERENCES 1. Mdoni-Builliet ,,\, Mor,-,,un R. Forth IL. Kingsh!v I'](], S~mdher,~ AA {I!)fi!}): Trisomv 14: ~Lnew entity will+in a(:tlt(t IlO]| lyn+l)l.)tfl.sti(: hmkemi.. (:unut+r (hme+t (]vlogt+ncl 43:35 3ft. 2. Bennett JM. C~flovsky l), Daniel MT, Flandrin (;, (;-alton I)A(;, (;ralni(:k ttR, Sultan (] (1982): Proposals for the (:lassit'iuatiml of the myelodysplast ic synd rmnes. BrJ Hacmatol 51:18!) 1!)9. 3. Copph+stone JA, Oscier 1)(;. Mufti GJ. Hamblin TJ {19~~61: Monocytiu skin infiltrati~m in chronic myelomonocyti¢: hmkae.mia. Clin l,ab Haematol 8:115 119. 4. (;roupe Fran(:ais (te, Cytogenetiqtm H e m a t o l o g i q u e (1986): (:yto~clmti(:s of (:hrotfi(: myelonl(> nouyti~:leuketnia. Cant:er(](met (]ytogenttt 21:11 3(). 5. Labal de Vinuesa M, Shivutsky 1, Larripa I ( 1987]: I)resent:e ()t isot:hromosomtts in httnlatolo,~i t:al disorders. Cai~t:er (;(;net (]ylogenel 25:47 54. 6, Shashady (;(;, Baumilhtr R(:( 1980): Philadelphia chrolnos(mle negative (:hr.ni. myeh)glm()us leukemia with lrisomy 1). Arch Pathol Lab Med 104:336 378. 7. Third M[(] Cooperative Stu(ly (;l'Otlp {1!}88}: Re(:omnmndalions [or a morphoh)gic, illllntlnologic and (:ytogenetic (MIC} working .lassifi(:ation of the primary and therapy-related my(dodyspUasti(: disorders. (]~ln(:er (;ene, t (]yto~4ent;t 32:1 10. 8. Pugh W(], Person M. Vardiman IW, Rowley II) {1,q85}: Philadelphia t:hromosomc negaliw! chronic myelogenous Icukaemia: a morphologi~:al reassessme, nt, Br I Hacmatol 50:457-457.