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Translocation t(8;16)(p11;p13) in acute nonlymphoblastic leukemia (M4) possibly secondary to Hodgkin's disease
SHORT COMMUNICATIONS Translocation t(8;16)(p11;p13) in Acute Nonlymphoblastic Leukemia (M4) Possibly Secondary to Hodgkin's Disease G. Barbata, P. Carbone, S. Mirto, A. Santoro, M. C. Giglio, and G. Granata
ABSTRACT: Simultaneous involvement of bands 8 p l l and 16p13 in a primary, even though rare, chromosomal translacation recentlx described in acute nanlymphocytic leukemia may be of crucial interest in some subtypes at" tbis acute leukemia, particularly in the manacytic farm. In the present report we describe this translacation in acute nonlymphoblustic leukemia FAB M4, passiblv secondary R) Hodgkin's disease, though it is also possible that the leukemia ma 5' have developed de nova. The aberration t(8:16)(pll:p13) was present in 100% of direct and cultured bone marrow cell preparutians. A v e r 5 high frequency of cells with nonclanal structural chromosome aberratians was also observed in peripheral blood eulhlres (more than 53%). Rundam translocatians and deletions constituted most of the. observed alteratians. These findings are discussed wilh regard to the relatianships between secondary lcukemias and intensive polychemotherapeutic treatments of primary neaplasias.
INTRODUCTION
Some chromosomal rearrangements are consistently associated with FAB subtypes of acute n o n l y m p h o b l a s t i c leukemia (ANLL) [1]. N o n r a n d o m associations with M4 or M5 ANLL are the rearrangements of 11q [2]. In acute monocytic leukemia, chromosomes 7 and 8 are also frequently involved (see Juneja et al. [3]). Recently, a rearrangement involving chromosomes 8 and 16 was described; these chromosomes are, in fact, involved in a reciprocal translocation with breakpoints localized at bands 8 p l l and 16p13. The t(8;16) mutation has been detected in different ANLL subtypes (M1, M2, M4, and M5) [2-8]. In some of these reports it has been suggested that the t(8;16) could be associated with monoblastic leukemia [2] and/or with acute myelomonocytic leukemia [7]. According to Juneja et al. [3], this abnormality may be of primary importance in the process of leukemogenesis of histiocytic/monocytic malignancies. In the recent Second MIC Cooperative Study Group 19], the cytogenetic abnormality t(8;16){p11;p13) was reported as associated with the M5b type of acute monocytic leukemia. We found this primary karyotypic change in acute leukemia secondary to Hodgkin's disease (HD). Our cytogenetic findings also show a striking presence (more than 53%) of random translocations and deletions. From tile Dipartimentodi BiologiaCc[lulare e della Sviluppo. A. Monrov.Sezimmdi Genetica, [lniw~rsilv of Palermo and the Divisionedi Ematologiadell'()spedale, V. (]ervello (S. M.), l'alermo. Italy. Address requests for reprints to Dr. Paolo Carbone, Dipartimenta di Biologia Cellulare e della Sviluppo, A. Monroy, Sezione di Genelica. via Archirafi 22, 90123 Palermo, Italy. Received April 29, 1988; accepted August 5, 1988.
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CASE REPORT A N D CYTOGENETIC STUDIES
M. F. A., a 38-year-old female, was first a d m i t t e d to the hospital in March 1986 because of a left laterocervical l y m p h o n o d a l mass present for 4 months. No other palpable masses or systemic s y m p t o m s were present. A surgical biopsy was diagnostic for HD, l y m p h o c y t e - d e p l e t e d form. The patient u n d e r w e n t complete clinical staging, including hepatic, splenic, and bilateral posterior iliac crest biopsies. Final sites of involvement were found in nodes of the mesentery and in retroperitoneal sites with both c o m p u t e d tomography (CT) scanning and LAG. According to the Ann Arbor criteria the patient was recorded as III2A stage. A c o m b i n e d modality treatment was started with four cycles of alternating MOPP/ABVD regimen and TLI including inverted Y and mantle fields. Radiotherapy (RT) was frequently deferred because of profound cytopenia, and mantle fields were not completed. In October 1986, 7 months after the diagnosis of HD and 37 days from the last RT dose, the patient was readmitted owing to diffuse bone pain and purpura. Physical examination was negative except for pallor and purpura; palpable masses were absent. The PB cell counts disclosed: hemoglobin [Hb) of 10.3 g/dl; hematocrit (Hot) of 29.7%; white blood cell count (WBC) of 8.7 x 10~'/L with 8% neutrophils, 4% lymphocytes, 2% myelocytes, and 86% blast cells; the platelet count was 20.0 x 10~/L. On morphologic examination the bone marrow a p p e a r e d infiltrated by blast cells heterogeneous in size, which presented irregular nuclear outline, dispersed chromatin, some prominent nucleoli, and a variable amount of basophilic and sometimes granular cytoplasm. The Sudan Black B stain was strongly positive in 80% of blast cells. The NASDCAE reaction was also positive with partial NaF inhibition. A diagnosis of ANLL, FAB-M4 subtype, was made. No h u m a n leukocyte antigen (HLA) identical donors were found, and the patient was treated with high doses of cytarabine (3 g/m 2 every 12 hours for 4 days). On day + 20 the patient died, during aplastic phase without bone marrow (BM) blasts, from Enterobacter cloacae septicemia. Cytogenetic studies were performed in November 1986 on direct and 24-hour cultured bone marrow cell preparations. Peripheral blood cells were cultured for 72 hours in the presence of p h y t o h e m a g g l u t i n i n (PHA) for constitutional karyotype analysis. Methods and techniques were those used routinely in our laboratory [10, 11]. Chromosomal abnormalities were referred to according to the ISCN [12]. RESULTS AND DISCUSSION
A]I 34 karyotyped cells from direct bone marrow preparations showed the t(8;16)(p11;p13) (Fig. 1). The same abnormality was present in all 16 cells from cultured bone marrow cell preparations. Only one of 15 cells from stimulated blood culture was found to have the t(8;16). A normal 46,XX karotype was seen in only six cells. Most (53.3%) of the stimulated l y m p h o c y t e s showed r a n d o m translocations and deletions. Cases with t(8;16) have been seen in hematologic neoplasias, though one or both breakpoints may be different from those u n d e r discussion here [5]. There have been several reports of t(8;16) with breakpoints at 8 p l l and 16p13, mainly seen in ANLL (Table 1 ). Both chromosomes 8 and 16 undergo rearrangements and are involved in aneuploidies ill hematologic neoplasias [5]. The long arms of c h r o m o s o m e 8 are specifically involved both in Burkitt l y m p h o m a and in acute l y m p h o c y t i c leukemia (ALL) L3 at band q24 and in ANLL M2 at band q22. Also, the short arms are involved in myelopr6liferative disorders at band p l l [1]. Total trisomies of c h r o m o s o m e 8 have been reported in p r e l e u k e m i c states, in blastic crisis of chronic myelocytic leukemia
t(8;16)(pll:p13) in ANLL (M4) Secondary to HD
129
m
-
.o
a . s
8
8p-
_
16p+16
Figure 1 Partial karyotype from four bone marrow cells showing the t(8;16)(p11;p13).
(CML), and in ANLL. As for c h r o m o s o m e 16, bands p13 and p22 have been found to be rearranged in ANLL [1, 91. According to Mitelman and Helm [13], five of 83 bands involved in primary cancer-associated rearrangements are localized on the long arms of c h r o m o s o m e 8 and two bands on c h r o m o s o m e 16 (16p13 and 16q22). Hitherto, no oncogene has been localized at bands 8 p l l or 16p13; however, because these bands are involved in changes associated with ANLL M5b [9], molecular investigations could better clarify this question. In a recent report Bernstein et al. [2] postulated that some genes involved in the monocytic differentiation may be localized at bands 8 p l l and 16p13 as well as at specific regions of 11q. According to the recent MIC classification [91, a form of M5b with leukemic cells demonstrating erythrophagocytosis is associated with t(8;16)(p11;p13). No erythrophagocytosis was present in our patient. On the basis of the literature dealing with leukemias secondary to HD [14-161, the case reported here is atypical both because of the brief period of time for the occurrence of the secondary ANLL, and because this last n e o p l a s m was not preceded by a p r e l e u k e m i c state. In the present paper we also report a high frequency of translocations and other structural c h r o m o s o m e aberrations in the peripheral blood, probably correlated with intensive chemotherapy. Chromosomal markers,
130
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Table 1 Cases reported 1 2 3 4 5 6
7 8 9 10 11 12 13
T r a n s l o c a t i o n t ( 8 : 1 6 ) ( p 1 1 ; p 1 3 ) in ANLL
Sex/age
Disease
t~'AB subtype
References
M/14 days M/5 days F/? F/34 years F/19 months F/15 years M/17 years M/10 months F/13.5 years F/29 years F/59 years F/32 years F/38 years
Histioeytosis/ANLI~ ANLL ANLL ANLL ANLL ANL1, ANLL ANI,L ANLL ANLL ANLL ANLL ANLL (secondary to HD)
M5b? MSa M1 M2 M5a M5b M5 M5b Unusual M4 Unusual M4 Unusual M4 M5 M4
Schoutell e,t a[. [21 I Be,rnstein et al, [4J Mitehnan [5] Ritter and Wei{len [8j Bernstein et al. J2] Heim el al. J6] Helm et al. [6] Heim et al. [6] Lai et al. [7] Lai et al. I7] Lai et al. [7] Juneja et al. [3] Present report
b a l a n c e d or u n b a l a n c e d t r a n s l o c a t i o n s , m i n u t e s , rings, a n d c h r o i n o s o m e r e a r r a n g e m e n t s h a v e b e e n r e p o r t e d in a b o u t 5 0 % of l e u k e m i a s s e c o n d a r y to HD [17]. In s e c o n d a r y l e u k e m i a s , t h e p r e s e n c e of t h e t(15;17) in t w o cases w i t h APL M3, of t h e t[8;21) in a case w i t h A N L L M2 [18], a n d of t h e t(9:22)(q34;q11) in a case w i t h ANLL M1 [19] is of p a r t i c u l a r i n t e r e s t . In a g r e e m e n t w i t h O h y a s h i k i et al. [19], w e t h i n k t h a t t h e e x p o s u r e to i n t e n s i v e c h e m o t h e r a p y m a y also be t h e c a u s e of primary chromosome mutations. In t h e case r e p o r t e d here, t h e t(8:16) c o u l d be a c o n s e q u e n c e of t h e c h e m o t h e r a p e u t i c t r e a t m e n t , to w h i c h t h e p a t i e n t w a s s u b m i t t e d b e c a u s e of t h e p r i m a r y neop l a s m . U n f o r t u n a t e l y , n o c y t o g e n e t i c s t u d y w a s c a r r i e d o u t d u r i n g t h e p r i m a r y neop l a s m p h a s e . We s u s p e c t , t h o u g h , t h a t t h e a b n o r m a l i t y o n t w o b a n d s i n v o l v e d in p r i m a r y c a n c e r - s p e c i f i c r e a r r a n g e i n e n t s ( 8 p l l a n d 16p13) [20] m i g h t h a v e determ i n e d t h e o c c u r r e n c e of t h e s e c o n d a r y n e o p l a s i a b y c o n f e r r i n g a s e l e c t i w ~, a d v a n tage o n t h e cells. This work was supported by Ministero Pubblic:a lstruzione (60%) and Progetto Finalizzato (372/M), Regione Sicilia. The authors are grate, ful to Mr. M. Noto for his technical assistance.
REFERENCES 1. Berger R, BIc~omfield CD, Sutherland GR (1985): Report of the committee on chromosome rearrangements in aeoplasia and on fragile sites. Human Gene Mapping 8. Cytogenet Cell Genet 40:490-535. 2. Bernstein R, Pinto MR, Spector I, Macdougall LG (1987): A unique 8;16 translocation in two infants with poorly differentiated monoblastic leukemia. Cancer Genet Cytogenet 24:213-220. 3. Juneja HS, Elder FEB. Rajaraman S (1987): Acute monoblastic leukemia with a single chromosomal rearrangement involving breakpoints on chromosome 8 and 16, 46,XX,t(8;16)(pll ;pl 3). Acta Haematol 78:1-5. 4. Bernstein R, Macdougall LG, Pinto MR (1984): Chromosome patterns in 26 South African children with acute nonlymphocytic leukemia (ANLL). Cancer Genet Cytogenet l 1:'199214. 5. Mitehnan F (1985): Catalog of Chromosome Aberrations in Cancer, 2od gd. Alan R. Liss, New York.
t(8;16)(p11;p13) in ANLL (M4) S e c o n d a r y to HD
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6. Helm S, Avanzi GC, Billstrom R, Kristoffersson U, Mandahl N, Bekassy AN, Garwicz S, Wiebe T, Pegoraro L, Falda M, Resegotti L, Mitelman F (1987): A new specific chromosomal rearrangement--t(8;16)(p11;p13)-- in acute monocytic leukaemia. Br ] Haematol 66:323-326. 7. Lai JL, Zandecki M, Jouet JP, Savary B, Lambiliotte A, Bauters 17, Cosson A, Deminatti M {1987): Three cases of translocation (8;16)(p11;p13] observed in acute myelomonocytic leukemia: A new specific subgroup? Cancer Genet Cytogenet 27:101-109. 8. Ritter HL Jr, Weiden PL (1987): Unusual association of bone marrow necrosis, disseminated intravascular coagulation, and a rare 8:16 chromosomal translocation in an adult patient with acute nonlymphocytic leukemia. Cancer Genet Cytogenet 24:243- 250. 9. Second MIC Cooperative Study Group (1988): Morphologic, Immunologic and Cytogenetic {MIC) working classification of the acute myeloid leukemias. Cancer Genel Cytogenet 30:1 15. 10. Carbone P, Granata G, Margiotta G, Barbata G, Majolino 1 (1982]: Ph' duplication, t(13q-;14q+) and trisomy 19 in a case with chronic nweloid leukemia in lymphoid blast crisis at presentation. Haematologica 67:595-604, 11. Carbone P, Barbata G, Mirto S, Marcen6 R, Leone S, Granata G (1984): Cytogenetic studies in five patients with myelofibrosis and myeloid metaplasia. Cancer Genet Cytogenet 12:209-215. 12. ISCN (19781: An International System for Human Cytogenetic Nomenclature {1978). Birth Defects: Original Article Series, Vol. XIV, No. 8 (The National Foundation, New York, 1978): also in Cytogenet Cell Genet 21:309-404 11978). 13. Heim S, Mitelman F (1987): Nineteen of 26 cellular oncogenes precisely localized in the human genoma map to one of the 83 bands involw~d in primary cancer-specific rearrangements. Hum Genet 75:70 72. 14. Pedersen-Bjergaard I, Larsen SO (1982): Incidence of acute nonlymphocytic leukemia, preleukemia, and acute myeloproliferative syndrome up to 10 years after treatment of Hodgkin's disease. N Eugl J Med 3(17:965 971. 15. Miche, ls SD, McKenna RW, Arthur DC, Brunning RD (1985): Therapy-related acute myeloid leukemia and myelodisplastic syndrome: A clinical and morphologic study of 65 cases. Blood 65:1364-1372. 16. Brusamoliuo E, Pagnucco G, Bernasconi C (1986): Acute leukemia occurring in a primary neoplasia (secondary leukemia). A review on biological, epidemiological and clinical aspects. Haematologica 71:60 83. 17. Papa G, Anselmo P, Cimino G, Mauro FR, Mandelli F (1985): Le leucemie, secondarie. Haematologica 70:199-204. 18. Fourth International Workshop on Chromosomes in Leukemia, 1982 (1984): Secondary leukemias associated with nenplasia: Treated and untreated. Cancer Genet Cytogenet 11:319-321. 19. Ohyashiki K, Kocova M, Ryan DH, Rowe JM, Sandberg AA (1986): Secondary acute myeloblastic leukemia with a Pb translocation in a treated Wegener's Granulomatosis. Cancer Genet Cytogenet 19:331-333. 20. Mitehnan F {1986): Clustering of breakpnints to specific chromosomal regions in human neoplasia. A survey of 5,345 cases. Hereditas 104:113 119. 21. Schouten TI, Hustinix TWJ, Scheres JMJC, Holland R, De Vaan GAM (1983]: Malignant histsocytosis. Clinical and cytogenetic studies in a newborn and a child. Cancer 52:12291236.
ABSTRACT: Simultaneous involvement of bands 8 p l l and 16p13 in a primary, even though rare, chromosomal translacation recentlx described in acute nanlymphocytic leukemia may be of crucial interest in some subtypes at" tbis acute leukemia, particularly in the manacytic farm. In the present report we describe this translacation in acute nonlymphoblustic leukemia FAB M4, passiblv secondary R) Hodgkin's disease, though it is also possible that the leukemia ma 5' have developed de nova. The aberration t(8:16)(pll:p13) was present in 100% of direct and cultured bone marrow cell preparutians. A v e r 5 high frequency of cells with nonclanal structural chromosome aberratians was also observed in peripheral blood eulhlres (more than 53%). Rundam translocatians and deletions constituted most of the. observed alteratians. These findings are discussed wilh regard to the relatianships between secondary lcukemias and intensive polychemotherapeutic treatments of primary neaplasias.
INTRODUCTION
Some chromosomal rearrangements are consistently associated with FAB subtypes of acute n o n l y m p h o b l a s t i c leukemia (ANLL) [1]. N o n r a n d o m associations with M4 or M5 ANLL are the rearrangements of 11q [2]. In acute monocytic leukemia, chromosomes 7 and 8 are also frequently involved (see Juneja et al. [3]). Recently, a rearrangement involving chromosomes 8 and 16 was described; these chromosomes are, in fact, involved in a reciprocal translocation with breakpoints localized at bands 8 p l l and 16p13. The t(8;16) mutation has been detected in different ANLL subtypes (M1, M2, M4, and M5) [2-8]. In some of these reports it has been suggested that the t(8;16) could be associated with monoblastic leukemia [2] and/or with acute myelomonocytic leukemia [7]. According to Juneja et al. [3], this abnormality may be of primary importance in the process of leukemogenesis of histiocytic/monocytic malignancies. In the recent Second MIC Cooperative Study Group 19], the cytogenetic abnormality t(8;16){p11;p13) was reported as associated with the M5b type of acute monocytic leukemia. We found this primary karyotypic change in acute leukemia secondary to Hodgkin's disease (HD). Our cytogenetic findings also show a striking presence (more than 53%) of random translocations and deletions. From tile Dipartimentodi BiologiaCc[lulare e della Sviluppo. A. Monrov.Sezimmdi Genetica, [lniw~rsilv of Palermo and the Divisionedi Ematologiadell'()spedale, V. (]ervello (S. M.), l'alermo. Italy. Address requests for reprints to Dr. Paolo Carbone, Dipartimenta di Biologia Cellulare e della Sviluppo, A. Monroy, Sezione di Genelica. via Archirafi 22, 90123 Palermo, Italy. Received April 29, 1988; accepted August 5, 1988.
127
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CASE REPORT A N D CYTOGENETIC STUDIES
M. F. A., a 38-year-old female, was first a d m i t t e d to the hospital in March 1986 because of a left laterocervical l y m p h o n o d a l mass present for 4 months. No other palpable masses or systemic s y m p t o m s were present. A surgical biopsy was diagnostic for HD, l y m p h o c y t e - d e p l e t e d form. The patient u n d e r w e n t complete clinical staging, including hepatic, splenic, and bilateral posterior iliac crest biopsies. Final sites of involvement were found in nodes of the mesentery and in retroperitoneal sites with both c o m p u t e d tomography (CT) scanning and LAG. According to the Ann Arbor criteria the patient was recorded as III2A stage. A c o m b i n e d modality treatment was started with four cycles of alternating MOPP/ABVD regimen and TLI including inverted Y and mantle fields. Radiotherapy (RT) was frequently deferred because of profound cytopenia, and mantle fields were not completed. In October 1986, 7 months after the diagnosis of HD and 37 days from the last RT dose, the patient was readmitted owing to diffuse bone pain and purpura. Physical examination was negative except for pallor and purpura; palpable masses were absent. The PB cell counts disclosed: hemoglobin [Hb) of 10.3 g/dl; hematocrit (Hot) of 29.7%; white blood cell count (WBC) of 8.7 x 10~'/L with 8% neutrophils, 4% lymphocytes, 2% myelocytes, and 86% blast cells; the platelet count was 20.0 x 10~/L. On morphologic examination the bone marrow a p p e a r e d infiltrated by blast cells heterogeneous in size, which presented irregular nuclear outline, dispersed chromatin, some prominent nucleoli, and a variable amount of basophilic and sometimes granular cytoplasm. The Sudan Black B stain was strongly positive in 80% of blast cells. The NASDCAE reaction was also positive with partial NaF inhibition. A diagnosis of ANLL, FAB-M4 subtype, was made. No h u m a n leukocyte antigen (HLA) identical donors were found, and the patient was treated with high doses of cytarabine (3 g/m 2 every 12 hours for 4 days). On day + 20 the patient died, during aplastic phase without bone marrow (BM) blasts, from Enterobacter cloacae septicemia. Cytogenetic studies were performed in November 1986 on direct and 24-hour cultured bone marrow cell preparations. Peripheral blood cells were cultured for 72 hours in the presence of p h y t o h e m a g g l u t i n i n (PHA) for constitutional karyotype analysis. Methods and techniques were those used routinely in our laboratory [10, 11]. Chromosomal abnormalities were referred to according to the ISCN [12]. RESULTS AND DISCUSSION
A]I 34 karyotyped cells from direct bone marrow preparations showed the t(8;16)(p11;p13) (Fig. 1). The same abnormality was present in all 16 cells from cultured bone marrow cell preparations. Only one of 15 cells from stimulated blood culture was found to have the t(8;16). A normal 46,XX karotype was seen in only six cells. Most (53.3%) of the stimulated l y m p h o c y t e s showed r a n d o m translocations and deletions. Cases with t(8;16) have been seen in hematologic neoplasias, though one or both breakpoints may be different from those u n d e r discussion here [5]. There have been several reports of t(8;16) with breakpoints at 8 p l l and 16p13, mainly seen in ANLL (Table 1 ). Both chromosomes 8 and 16 undergo rearrangements and are involved in aneuploidies ill hematologic neoplasias [5]. The long arms of c h r o m o s o m e 8 are specifically involved both in Burkitt l y m p h o m a and in acute l y m p h o c y t i c leukemia (ALL) L3 at band q24 and in ANLL M2 at band q22. Also, the short arms are involved in myelopr6liferative disorders at band p l l [1]. Total trisomies of c h r o m o s o m e 8 have been reported in p r e l e u k e m i c states, in blastic crisis of chronic myelocytic leukemia
t(8;16)(pll:p13) in ANLL (M4) Secondary to HD
129
m
-
.o
a . s
8
8p-
_
16p+16
Figure 1 Partial karyotype from four bone marrow cells showing the t(8;16)(p11;p13).
(CML), and in ANLL. As for c h r o m o s o m e 16, bands p13 and p22 have been found to be rearranged in ANLL [1, 91. According to Mitelman and Helm [13], five of 83 bands involved in primary cancer-associated rearrangements are localized on the long arms of c h r o m o s o m e 8 and two bands on c h r o m o s o m e 16 (16p13 and 16q22). Hitherto, no oncogene has been localized at bands 8 p l l or 16p13; however, because these bands are involved in changes associated with ANLL M5b [9], molecular investigations could better clarify this question. In a recent report Bernstein et al. [2] postulated that some genes involved in the monocytic differentiation may be localized at bands 8 p l l and 16p13 as well as at specific regions of 11q. According to the recent MIC classification [91, a form of M5b with leukemic cells demonstrating erythrophagocytosis is associated with t(8;16)(p11;p13). No erythrophagocytosis was present in our patient. On the basis of the literature dealing with leukemias secondary to HD [14-161, the case reported here is atypical both because of the brief period of time for the occurrence of the secondary ANLL, and because this last n e o p l a s m was not preceded by a p r e l e u k e m i c state. In the present paper we also report a high frequency of translocations and other structural c h r o m o s o m e aberrations in the peripheral blood, probably correlated with intensive chemotherapy. Chromosomal markers,
130
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Table 1 Cases reported 1 2 3 4 5 6
7 8 9 10 11 12 13
T r a n s l o c a t i o n t ( 8 : 1 6 ) ( p 1 1 ; p 1 3 ) in ANLL
Sex/age
Disease
t~'AB subtype
References
M/14 days M/5 days F/? F/34 years F/19 months F/15 years M/17 years M/10 months F/13.5 years F/29 years F/59 years F/32 years F/38 years
Histioeytosis/ANLI~ ANLL ANLL ANLL ANLL ANL1, ANLL ANI,L ANLL ANLL ANLL ANLL ANLL (secondary to HD)
M5b? MSa M1 M2 M5a M5b M5 M5b Unusual M4 Unusual M4 Unusual M4 M5 M4
Schoutell e,t a[. [21 I Be,rnstein et al, [4J Mitehnan [5] Ritter and Wei{len [8j Bernstein et al. J2] Heim el al. J6] Helm et al. [6] Heim et al. [6] Lai et al. [7] Lai et al. I7] Lai et al. [7] Juneja et al. [3] Present report
b a l a n c e d or u n b a l a n c e d t r a n s l o c a t i o n s , m i n u t e s , rings, a n d c h r o i n o s o m e r e a r r a n g e m e n t s h a v e b e e n r e p o r t e d in a b o u t 5 0 % of l e u k e m i a s s e c o n d a r y to HD [17]. In s e c o n d a r y l e u k e m i a s , t h e p r e s e n c e of t h e t(15;17) in t w o cases w i t h APL M3, of t h e t[8;21) in a case w i t h A N L L M2 [18], a n d of t h e t(9:22)(q34;q11) in a case w i t h ANLL M1 [19] is of p a r t i c u l a r i n t e r e s t . In a g r e e m e n t w i t h O h y a s h i k i et al. [19], w e t h i n k t h a t t h e e x p o s u r e to i n t e n s i v e c h e m o t h e r a p y m a y also be t h e c a u s e of primary chromosome mutations. In t h e case r e p o r t e d here, t h e t(8:16) c o u l d be a c o n s e q u e n c e of t h e c h e m o t h e r a p e u t i c t r e a t m e n t , to w h i c h t h e p a t i e n t w a s s u b m i t t e d b e c a u s e of t h e p r i m a r y neop l a s m . U n f o r t u n a t e l y , n o c y t o g e n e t i c s t u d y w a s c a r r i e d o u t d u r i n g t h e p r i m a r y neop l a s m p h a s e . We s u s p e c t , t h o u g h , t h a t t h e a b n o r m a l i t y o n t w o b a n d s i n v o l v e d in p r i m a r y c a n c e r - s p e c i f i c r e a r r a n g e i n e n t s ( 8 p l l a n d 16p13) [20] m i g h t h a v e determ i n e d t h e o c c u r r e n c e of t h e s e c o n d a r y n e o p l a s i a b y c o n f e r r i n g a s e l e c t i w ~, a d v a n tage o n t h e cells. This work was supported by Ministero Pubblic:a lstruzione (60%) and Progetto Finalizzato (372/M), Regione Sicilia. The authors are grate, ful to Mr. M. Noto for his technical assistance.
REFERENCES 1. Berger R, BIc~omfield CD, Sutherland GR (1985): Report of the committee on chromosome rearrangements in aeoplasia and on fragile sites. Human Gene Mapping 8. Cytogenet Cell Genet 40:490-535. 2. Bernstein R, Pinto MR, Spector I, Macdougall LG (1987): A unique 8;16 translocation in two infants with poorly differentiated monoblastic leukemia. Cancer Genet Cytogenet 24:213-220. 3. Juneja HS, Elder FEB. Rajaraman S (1987): Acute monoblastic leukemia with a single chromosomal rearrangement involving breakpoints on chromosome 8 and 16, 46,XX,t(8;16)(pll ;pl 3). Acta Haematol 78:1-5. 4. Bernstein R, Macdougall LG, Pinto MR (1984): Chromosome patterns in 26 South African children with acute nonlymphocytic leukemia (ANLL). Cancer Genet Cytogenet l 1:'199214. 5. Mitehnan F (1985): Catalog of Chromosome Aberrations in Cancer, 2od gd. Alan R. Liss, New York.
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