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Translocation t(3;21)(q26;q22) in acute myeloblastic leukemia secondary to polycythemia vera
Translocation t(3;21)(q26;q22) in Acute Myeloblastic Leukemia Secondary to Polycythemia Vera Nicole Dastugue, Jacques Pris, and Pierre Colombies
ABSTRACT: A case of acute myeloblastic leukemia secondary to polycythemia vera suggests that the
t(3;21) translocation is not restricted to blastic phases of chronic myelocytic leukemia (CML) but can be associated with blastic phases occurring after other myeloproliferative syndromes. All published cases were in myeloid crises. Furthermore. this translocation may have been induced by mutagenic effects of either :~2por various chemotherapies administered in this case. In the nine cases reported (including ours), hydroxyurea and busulfan were most frequently used (each drug was used separately in six cases and in association in three cases). Even if the t(3;21) translocation is partly therapy induced, this chromosomal abnormality appears to characterize myelaid crises of myeloproliferative syndromes (often CML. seldom polycythemia vera).
T r a n s l o c a t i o n t(3;21)(q26;q22) has b e e n r e p o r t e d so far in the blastic phase of c h r o n i c m y e l o i d l e u k e m i a (CML) [1 5]. H o w e v e r , R u b i n et al. [1] d e s c r i b e d two u n p u b l i s h e d cases in w h i c h the t(3;21) was a s s o c i a t e d w i t h a s e c o n d a r y m y e l o d y s p l a s t i c s y n d r o m e after c h e m o t h e r a p y for p r e v i o u s m a l i g n a n c y . We report a case of p o l y c y t h e m i a vera (PV) t r a n s f o r m e d into acute m y e l o b l a s t i c l e u k e m i a (AML) w i t h a t(3;21)(q26;q22). A 47-year-old man was d i a g n o s e d as h a v i n g PV in January 1978. He had s p l e n o m e g aly and laboratory data of typical PV. His h e m o g l o b i n level was 22 g/dL, his red blood cell c o u n t was 7.4 x 10~/L, his platelet c o u n t was 100 x 10~/L, and his w h i t e blood cell c o u n t was 7.8 x 109/L w i t h 68% n e u t r o p h i l s , 1% e o s i n o p h i l s , 27% l y m p h o c y t e s , and 4% m o n o c y t e s . His e r y t h r o c y t e s e d i m e n t a t i o n rate was 0, his total blood v o l u m e was 140 ml/kg, and his total e r y t h r o c y t e v o l u m e was 102 ml/kg. A b o n e m a r r o w aspirate s h o w e d n o r m a l c e l l u l a r i t y w i t h 45% g r a n u l o c y t e s and 48% erythroblasts. Bone m a r r o w b i o p s y c o n f i r m e d the d i a g n o s i s of PV, and the patient was treated w i t h c h l o r a m b u c i l for I year, f o l l o w e d by two injections of :~2P (7/xCi), one in 1979 and the s e c o n d in 1982; h y d r o x y u r e a was t h e n a d m i n i s t e r e d for 2 m o r e years and, finally, a n o t h e r alkylating agent, p i p o b r o m a n , was a d m i n i s t e r e d for 2 years. In S e p t e m b e r 1988, he d e v e l o p e d an A M L t y p e M2 a c c o r d i n g to the FAB classification, w i t h o u t a p r e v i o u s d e t e c t a b l e m y e l o d y s p l a s t i c s y n d r o m e . C y t o g e n e t i c analysis p e r f o r m e d at this stage r e v e a l e d the k a r y o t y p e 4 6 , X Y , t ( 3 ; 2 1 ) ( q 2 6 ; q 2 2 ) ( 3 7 ) / 4 7 , X Y ,
From the Laboratoire Central d'Hematologie et de G6n6tique C. R. T. S (N. D.. P. C.), and Service d'Hdmato logie, H6pital Purpan (J. P.), Toulouse, France. Address reprint requests to: Dr. N. Dastugue at Laboratoire Central d'H~matologie el de G6n6tique, Centre R~gional de Transfusion Sanguine, Chu Purpan. 31052 Toulouse. Cedex France. Received June 8, 1989; accepted June 28, 1989.
275 c~2~1990 Elsevier Science Publishing Co.. Inc. 655 Avenue of the Americas, New York, NY 10010
Cancer Genet Cytogenet 44:275 276 (1990) 0165-4608/90/$03.50
276
N. D a s t u g u e et al.
¢ RHG
GTG
Figure 1
Partial karyotype showing t(3:21)(q26:q22).
+ 8(2)/46,XY, del(20q)(2). In t h e t e r m i n a l p h a s e , c l o n a l e v o l u t i o n o c c u r r e d 47,XY, + 9,t(3;21)(q26;q22) {two cells)/48,XY, + 9, + 12,t(3;21)(q26;q22) (28 cells).
REFERENCES 1. Rubin CM, Larson RA, Bitter MA, Carrino JJ, Le Beau MM, l)iaz MO, Rowle, y ll) (1987): Association of a chromosomal 3;21 translocation with the blast phase of chronic myelogenous leukemia. Blood 70:1338 1348. 2. Diez-Martin )L, Dewald GW, Pierre RV (1988): Possible cytogenetic distinction between lymphoid and myeloid blast crisis in chronic granulocytic leukemia. Am l llematol 27:194 203. 3. Aventin A, Mecucci C, Van Den Berghe H (1988): Blastic phase of Ph'-positive chronic myeloid leukemia and t(3;21). Blood 72:369. 4. Coyle T, Najfeld V (1988): Translocalion (3;21) in Philadelphia chromosome-positive chronic myelogenous leukemia prior to the onset of blastic crisis. Am ] tlematol 27:56 59. 5. Aventin A, Viaplana ], Zuazu 1, Brunet S, Pujol-Moix N (1988): Philadelphia-pnsitiw.~chronic myeloid leukemia with translocation t(3;21 ). Cancer Genet Cytogenet 35:133- 134.
ABSTRACT: A case of acute myeloblastic leukemia secondary to polycythemia vera suggests that the
t(3;21) translocation is not restricted to blastic phases of chronic myelocytic leukemia (CML) but can be associated with blastic phases occurring after other myeloproliferative syndromes. All published cases were in myeloid crises. Furthermore. this translocation may have been induced by mutagenic effects of either :~2por various chemotherapies administered in this case. In the nine cases reported (including ours), hydroxyurea and busulfan were most frequently used (each drug was used separately in six cases and in association in three cases). Even if the t(3;21) translocation is partly therapy induced, this chromosomal abnormality appears to characterize myelaid crises of myeloproliferative syndromes (often CML. seldom polycythemia vera).
T r a n s l o c a t i o n t(3;21)(q26;q22) has b e e n r e p o r t e d so far in the blastic phase of c h r o n i c m y e l o i d l e u k e m i a (CML) [1 5]. H o w e v e r , R u b i n et al. [1] d e s c r i b e d two u n p u b l i s h e d cases in w h i c h the t(3;21) was a s s o c i a t e d w i t h a s e c o n d a r y m y e l o d y s p l a s t i c s y n d r o m e after c h e m o t h e r a p y for p r e v i o u s m a l i g n a n c y . We report a case of p o l y c y t h e m i a vera (PV) t r a n s f o r m e d into acute m y e l o b l a s t i c l e u k e m i a (AML) w i t h a t(3;21)(q26;q22). A 47-year-old man was d i a g n o s e d as h a v i n g PV in January 1978. He had s p l e n o m e g aly and laboratory data of typical PV. His h e m o g l o b i n level was 22 g/dL, his red blood cell c o u n t was 7.4 x 10~/L, his platelet c o u n t was 100 x 10~/L, and his w h i t e blood cell c o u n t was 7.8 x 109/L w i t h 68% n e u t r o p h i l s , 1% e o s i n o p h i l s , 27% l y m p h o c y t e s , and 4% m o n o c y t e s . His e r y t h r o c y t e s e d i m e n t a t i o n rate was 0, his total blood v o l u m e was 140 ml/kg, and his total e r y t h r o c y t e v o l u m e was 102 ml/kg. A b o n e m a r r o w aspirate s h o w e d n o r m a l c e l l u l a r i t y w i t h 45% g r a n u l o c y t e s and 48% erythroblasts. Bone m a r r o w b i o p s y c o n f i r m e d the d i a g n o s i s of PV, and the patient was treated w i t h c h l o r a m b u c i l for I year, f o l l o w e d by two injections of :~2P (7/xCi), one in 1979 and the s e c o n d in 1982; h y d r o x y u r e a was t h e n a d m i n i s t e r e d for 2 m o r e years and, finally, a n o t h e r alkylating agent, p i p o b r o m a n , was a d m i n i s t e r e d for 2 years. In S e p t e m b e r 1988, he d e v e l o p e d an A M L t y p e M2 a c c o r d i n g to the FAB classification, w i t h o u t a p r e v i o u s d e t e c t a b l e m y e l o d y s p l a s t i c s y n d r o m e . C y t o g e n e t i c analysis p e r f o r m e d at this stage r e v e a l e d the k a r y o t y p e 4 6 , X Y , t ( 3 ; 2 1 ) ( q 2 6 ; q 2 2 ) ( 3 7 ) / 4 7 , X Y ,
From the Laboratoire Central d'Hematologie et de G6n6tique C. R. T. S (N. D.. P. C.), and Service d'Hdmato logie, H6pital Purpan (J. P.), Toulouse, France. Address reprint requests to: Dr. N. Dastugue at Laboratoire Central d'H~matologie el de G6n6tique, Centre R~gional de Transfusion Sanguine, Chu Purpan. 31052 Toulouse. Cedex France. Received June 8, 1989; accepted June 28, 1989.
275 c~2~1990 Elsevier Science Publishing Co.. Inc. 655 Avenue of the Americas, New York, NY 10010
Cancer Genet Cytogenet 44:275 276 (1990) 0165-4608/90/$03.50
276
N. D a s t u g u e et al.
¢ RHG
GTG
Figure 1
Partial karyotype showing t(3:21)(q26:q22).
+ 8(2)/46,XY, del(20q)(2). In t h e t e r m i n a l p h a s e , c l o n a l e v o l u t i o n o c c u r r e d 47,XY, + 9,t(3;21)(q26;q22) {two cells)/48,XY, + 9, + 12,t(3;21)(q26;q22) (28 cells).
REFERENCES 1. Rubin CM, Larson RA, Bitter MA, Carrino JJ, Le Beau MM, l)iaz MO, Rowle, y ll) (1987): Association of a chromosomal 3;21 translocation with the blast phase of chronic myelogenous leukemia. Blood 70:1338 1348. 2. Diez-Martin )L, Dewald GW, Pierre RV (1988): Possible cytogenetic distinction between lymphoid and myeloid blast crisis in chronic granulocytic leukemia. Am l llematol 27:194 203. 3. Aventin A, Mecucci C, Van Den Berghe H (1988): Blastic phase of Ph'-positive chronic myeloid leukemia and t(3;21). Blood 72:369. 4. Coyle T, Najfeld V (1988): Translocalion (3;21) in Philadelphia chromosome-positive chronic myelogenous leukemia prior to the onset of blastic crisis. Am ] tlematol 27:56 59. 5. Aventin A, Viaplana ], Zuazu 1, Brunet S, Pujol-Moix N (1988): Philadelphia-pnsitiw.~chronic myeloid leukemia with translocation t(3;21 ). Cancer Genet Cytogenet 35:133- 134.