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Trisomy of chromosome 22 in acute myelomonocytic leukemia
SHORT COMMUNICATION Trisomy of Chromosome 22 in Acute Myelomonocytic Leukemia Menco M. G. Niemeyer, Hans L. Haak, Els Augustinus, Jos6 I. den Nijs-van Weert, and Christiaan H. W. Leeksma
A patient with acute myelomonocytic leukemia type M4, with a trisomy 22 as the only chromosomal abnormality is reported. All six previously published cases with this anomaly had acute myeloid leukemia. The subtype was AMMoL in five patients, and the subtype of the sixth one was not indicated.
ABSTRACT:
INTRODUCTION
During recent years a number of acquired clonal chromosomal abnormalities have been reported, correlating with particular subtypes of acute n o n l y m p h o c y t i c leukemia (ANLL) and characteristic morphologic and clinical features [1-5]. We have observed a patient with acute m y e l o m o n o c y t i c leukemia (AMMoL) who had trisomy of chromosome #22 as the only abnormality.
CASE REPORT
A 73 year old w o m a n was admitted because of severe d y s p n e a on exertion. Her past medical history was unremarkable. Physical examination revealed pallor with absence of organomegaly or l y m p h a d e n o p a t h y , and no leukemic infiltrates in the skin. The concentration of hemoglobin was 5.4 mmol/1, platelets 35 x 10 9, WBC count 97 x 109/1 with 14% blast cells, 4% segmented neutrophits, 15% lymphocytes, and 67% monocytes and m o n o c y t o i d myelocytes. Bone marrow smears revealed a hypercellular bone marrow with severe decreased erythropoiesis, few megakaryocytes, and about 80% blast cells, monocytes, promonocytes, and m o n o c y t o i d myelocytes (Fig. 1). Cytochemical studies confirmed the m y e l o m o n o c y t i c nature of the leukemia suggested by the M a y - G r i i n w a l d stain. In the Sudan black B stain, a coarse localized pattern was found in about 40% of the cells and a scattered granular pattern in about 60%. In a dual esterase stain, a large fraction of the cells showed a strong reaction for naphthol acetate esterase blocked by NaF, and another fraction of cells with a strong chloroacetate esterase reaction. The periodic a c i d - S c h i f f stain showed a diffuse finely granular pattern. Therefore, a diagnosis of AMMoL M4 was made. Combined c h e m o t h e r a p y (teniposide, cytosine arabinoside, vinblastine, and
From the Department of Hematology,Municipal Hospital Leyenburg,The Hague, The Netherlands. Address requests for reprints to Dr. C. H. W. Leeksma, Department of Hematology, Municipal Hospital Leyenburg, Leyweg 275, 2545 CH The Hague, The Netherlands. Received May 16, 1985; accepted August 12, 1985.
371 © 1986 Elsevier Science Publishing Co., Inc.
Cancer Genet Cytogenet 20:371-374 (1986}
52 Vanderbilt Ave., New York, NY 10017
0165-4608/86/$03.50
372
M.M.G.
N i e m e y e r et al.
F i g u r e 1 Bone marrow histology. Note numerous monocytoid cells and absence of erythropoiesis. Methyl-methacrylate, Gallamine-Giemsa x 600. Courtesy of J. te Velde. p r e d n i s o n e ) was a d m i n i s t e r e d , but the r e s p o n s e was p o o r and the patient had to be m a i n t a i n e d on b l o o d transfusions. She d i e d after 4.5 m o n t h s of s e p t i c e m i c and hemorrhagic complications.
CHROMOSOME STUDY C h r o m o s o m e slides of p e r i p h e r a l b l o o d cells w e r e p r e p a r e d by a hot b a n d i n g m e t h o d r e c e n t l y r e p o r t e d [6], and s t a i n e d w i t h Giemsa. A 24-hour u n s t i m u l a t e d c u l t u r e s h o w e d : 4 6 , X X = 7, 4 7 , X X , + 2 2 = 8 (Fig, 2). A 9 6 - h o u r c u l t u r e w i t h P H A s h o w e d : 4 6 , X X = 12.
DISCUSSION T r i s o m y 22 (Fig. 2) as the o n l y k a r y o t y p i c a n o m a l y is of rare o c c u r r e n c e ; h o w e v e r , it has b e e n d e s c r i b e d m o r e f r e q u e n t l y in c o n j u n c t i o n w i t h o t h e r c h r o m o s o m a l abn o r m a l i t i e s . U n t i l n o w , as far as w e c o u l d ascertain, o n l y six cases w i t h t r i s o m y 22 Table 1
Patients w i t h t r i s o m y 22
Karyotype
Age (yr)
FAB diagnosis
Remission
Survival (mo)
Ref.
47,XX, + 22 46,XY/47,XY, + 22 47,XY, + 22 46,XX/47,XX, + 22 46,XY/47,XY, + 22 46,XY/47,XY, + 22 4B,XX/47,XX, + 22
19 child 22 27 10 58 73
U M4 M4 M4 M4 M4 M4
yes yes yes no yes yes no
U 18 U 1 18 22 5
[7] [8] [9] [101 [11] [12] [Present case]
15
14
2O
Karyotype: 47,XX, + 22.
13
19
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as the sole a b n o r m a l i t y h a v e b e e n r e p o r t e d [7-12]. T h e s e w e r e all cases of ANLL. In one case, the s u b t y p e was not r e p o r t e d ; the o t h e r five cases w e r e all A M M o L (Table 1). The finding in t h e s e patients w i t h t r i s o m y 22 suggest an association w i t h A M M o L , no r e l a t i o n w i t h age and sex, a n d no history of m u t a g e n i c exposure. Alt h o u g h no r e m i s s i o n was o b t a i n e d in our case, o t h e r studies h a v e s h o w n a substantial r e m i s s i o n rate. T h e d u r a t i o n of t h e s e r e m i s s i o n s a p p e a r s to be about average for this disorder.
REFERENCES 1. Rowley JD (1973): Identification of a translocation with quinacrine fluorescence in a patient with acute leukemia. Ann Genet 16:109. 2. Rowley JD, Colomb HM, Dougherty C (1977): 15/17 Translocation, a consistant chromosomal change in acute promyelocytic leukemia. Lancet i:549-550. 3. Berger R, Bergheim A, Siguax F, Daniel MFH, Valensi F, Flandrin G (1982): Acute monocytic leukemia chromosome studies. Leuk Res 6:17-26. 4. Hagemeyer A, H~ihlen K, Sizoo W, Abels J (1982): Translocation (9;11) (p21;q23) in three cases of acute monoblastic leukemia. Cancer Genet Cytogenet 5:95-105. 5. Lebeau MM Larson RA, Bitter MA, Vardiman JW, Golomb HM, Rowley JD (1983): Association of an inversion of chromosome 16 with abnormal marrow eosinophils in acute myelomonocytic leukemia: A unique cytogenetic-clinic-pathological association. N Engl J Med 309:630-636. 6. Nijs JI den, Gonggrijp HS, Augustinus E, Leeksma CHW (1985): A simple G-banding method for leukemic methaphases. Cancer Genet Cytogenet 15:373-374. 7. Oshimura MS, Hayata J, Kakati S, Sandberg AA (1976): Chromosomes and causation of human cancer and leukemia. XVII Banding studies in acute myeloblastic leukemia (AML). Cancer 38:748-761. 8. Zueler WW, Inoue S, Thompson RI, Ottenbreit MJ (1976): Long-term cytogenetic studies in acute leukemia of children; The nature of relapse. Am J Haematol 1:143-190. 9. Shiloh Y, Naparstek E, Cohen MM (1979): Cytogenetic investigation of leukemic and preleukemic disorders. Israel J Med Sci 15:500-506. 10. Mitelman F, Nilsson PG, Brandt L, Alimena G, Gastaldi R, Dallapiccola B (1981): Chromosome pattern, occupation, and clinical features in patients with acute nonlymphocytic leukemia. Cancer Genet Cytogenet 4:197-214. 11. Bernard P, Reiffers J, Lacombe F, Dachary D, Bavid B, Boisseau MR, Broustet A (1982): Prognostic value of age and bone marrow karyotype in 78 adults with myelogenous leukemia. Cancer Genet Cytogenet 7:153-163. 12. Brodeur GM, Williams DL, Kalwinsky DK, Williams KJ, Dahl GV (1983): Cytogenetic features of acute nonlymphoblastic leukemia in 78 children and adolescents. Cancer Genet Cytogenet 8:93-105. 13. McCarthy DM, Rassool FV, Goldman JM, Graham S, Birnie GD (1984): Genomic alterations involving the c-myc proto-oncogene locus during the evolution of a case of chronic granulocytic leukemia. Lancet ii:1362-1365.
ADDENDUM After c o m p l e t i o n of this c o m m u n i c a t i o n w e b e c a m e a w a r e of a report on a b n o r m a l ities of c h r o m o s o m e # 2 2 . In this report three cases w i t h an extra c h r o m o s o m e # 2 2 , all three w i t h M4 m o r p h o l o g y , are m e n t i o n e d (Fourth I n t e r n a t i o n a l W o r k s h o p on C h r o m o s o m e s in L e u k e m i a , 1982 (1984): A b n o r m a l i t i e s of c h r o m o s o m e 22. C a n c e r G e n e t Cytogent 11:316-318).
A patient with acute myelomonocytic leukemia type M4, with a trisomy 22 as the only chromosomal abnormality is reported. All six previously published cases with this anomaly had acute myeloid leukemia. The subtype was AMMoL in five patients, and the subtype of the sixth one was not indicated.
ABSTRACT:
INTRODUCTION
During recent years a number of acquired clonal chromosomal abnormalities have been reported, correlating with particular subtypes of acute n o n l y m p h o c y t i c leukemia (ANLL) and characteristic morphologic and clinical features [1-5]. We have observed a patient with acute m y e l o m o n o c y t i c leukemia (AMMoL) who had trisomy of chromosome #22 as the only abnormality.
CASE REPORT
A 73 year old w o m a n was admitted because of severe d y s p n e a on exertion. Her past medical history was unremarkable. Physical examination revealed pallor with absence of organomegaly or l y m p h a d e n o p a t h y , and no leukemic infiltrates in the skin. The concentration of hemoglobin was 5.4 mmol/1, platelets 35 x 10 9, WBC count 97 x 109/1 with 14% blast cells, 4% segmented neutrophits, 15% lymphocytes, and 67% monocytes and m o n o c y t o i d myelocytes. Bone marrow smears revealed a hypercellular bone marrow with severe decreased erythropoiesis, few megakaryocytes, and about 80% blast cells, monocytes, promonocytes, and m o n o c y t o i d myelocytes (Fig. 1). Cytochemical studies confirmed the m y e l o m o n o c y t i c nature of the leukemia suggested by the M a y - G r i i n w a l d stain. In the Sudan black B stain, a coarse localized pattern was found in about 40% of the cells and a scattered granular pattern in about 60%. In a dual esterase stain, a large fraction of the cells showed a strong reaction for naphthol acetate esterase blocked by NaF, and another fraction of cells with a strong chloroacetate esterase reaction. The periodic a c i d - S c h i f f stain showed a diffuse finely granular pattern. Therefore, a diagnosis of AMMoL M4 was made. Combined c h e m o t h e r a p y (teniposide, cytosine arabinoside, vinblastine, and
From the Department of Hematology,Municipal Hospital Leyenburg,The Hague, The Netherlands. Address requests for reprints to Dr. C. H. W. Leeksma, Department of Hematology, Municipal Hospital Leyenburg, Leyweg 275, 2545 CH The Hague, The Netherlands. Received May 16, 1985; accepted August 12, 1985.
371 © 1986 Elsevier Science Publishing Co., Inc.
Cancer Genet Cytogenet 20:371-374 (1986}
52 Vanderbilt Ave., New York, NY 10017
0165-4608/86/$03.50
372
M.M.G.
N i e m e y e r et al.
F i g u r e 1 Bone marrow histology. Note numerous monocytoid cells and absence of erythropoiesis. Methyl-methacrylate, Gallamine-Giemsa x 600. Courtesy of J. te Velde. p r e d n i s o n e ) was a d m i n i s t e r e d , but the r e s p o n s e was p o o r and the patient had to be m a i n t a i n e d on b l o o d transfusions. She d i e d after 4.5 m o n t h s of s e p t i c e m i c and hemorrhagic complications.
CHROMOSOME STUDY C h r o m o s o m e slides of p e r i p h e r a l b l o o d cells w e r e p r e p a r e d by a hot b a n d i n g m e t h o d r e c e n t l y r e p o r t e d [6], and s t a i n e d w i t h Giemsa. A 24-hour u n s t i m u l a t e d c u l t u r e s h o w e d : 4 6 , X X = 7, 4 7 , X X , + 2 2 = 8 (Fig, 2). A 9 6 - h o u r c u l t u r e w i t h P H A s h o w e d : 4 6 , X X = 12.
DISCUSSION T r i s o m y 22 (Fig. 2) as the o n l y k a r y o t y p i c a n o m a l y is of rare o c c u r r e n c e ; h o w e v e r , it has b e e n d e s c r i b e d m o r e f r e q u e n t l y in c o n j u n c t i o n w i t h o t h e r c h r o m o s o m a l abn o r m a l i t i e s . U n t i l n o w , as far as w e c o u l d ascertain, o n l y six cases w i t h t r i s o m y 22 Table 1
Patients w i t h t r i s o m y 22
Karyotype
Age (yr)
FAB diagnosis
Remission
Survival (mo)
Ref.
47,XX, + 22 46,XY/47,XY, + 22 47,XY, + 22 46,XX/47,XX, + 22 46,XY/47,XY, + 22 46,XY/47,XY, + 22 4B,XX/47,XX, + 22
19 child 22 27 10 58 73
U M4 M4 M4 M4 M4 M4
yes yes yes no yes yes no
U 18 U 1 18 22 5
[7] [8] [9] [101 [11] [12] [Present case]
15
14
2O
Karyotype: 47,XX, + 22.
13
19
Figure 2
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374
M . M . (;. N i e m e v e r et al.
as the sole a b n o r m a l i t y h a v e b e e n r e p o r t e d [7-12]. T h e s e w e r e all cases of ANLL. In one case, the s u b t y p e was not r e p o r t e d ; the o t h e r five cases w e r e all A M M o L (Table 1). The finding in t h e s e patients w i t h t r i s o m y 22 suggest an association w i t h A M M o L , no r e l a t i o n w i t h age and sex, a n d no history of m u t a g e n i c exposure. Alt h o u g h no r e m i s s i o n was o b t a i n e d in our case, o t h e r studies h a v e s h o w n a substantial r e m i s s i o n rate. T h e d u r a t i o n of t h e s e r e m i s s i o n s a p p e a r s to be about average for this disorder.
REFERENCES 1. Rowley JD (1973): Identification of a translocation with quinacrine fluorescence in a patient with acute leukemia. Ann Genet 16:109. 2. Rowley JD, Colomb HM, Dougherty C (1977): 15/17 Translocation, a consistant chromosomal change in acute promyelocytic leukemia. Lancet i:549-550. 3. Berger R, Bergheim A, Siguax F, Daniel MFH, Valensi F, Flandrin G (1982): Acute monocytic leukemia chromosome studies. Leuk Res 6:17-26. 4. Hagemeyer A, H~ihlen K, Sizoo W, Abels J (1982): Translocation (9;11) (p21;q23) in three cases of acute monoblastic leukemia. Cancer Genet Cytogenet 5:95-105. 5. Lebeau MM Larson RA, Bitter MA, Vardiman JW, Golomb HM, Rowley JD (1983): Association of an inversion of chromosome 16 with abnormal marrow eosinophils in acute myelomonocytic leukemia: A unique cytogenetic-clinic-pathological association. N Engl J Med 309:630-636. 6. Nijs JI den, Gonggrijp HS, Augustinus E, Leeksma CHW (1985): A simple G-banding method for leukemic methaphases. Cancer Genet Cytogenet 15:373-374. 7. Oshimura MS, Hayata J, Kakati S, Sandberg AA (1976): Chromosomes and causation of human cancer and leukemia. XVII Banding studies in acute myeloblastic leukemia (AML). Cancer 38:748-761. 8. Zueler WW, Inoue S, Thompson RI, Ottenbreit MJ (1976): Long-term cytogenetic studies in acute leukemia of children; The nature of relapse. Am J Haematol 1:143-190. 9. Shiloh Y, Naparstek E, Cohen MM (1979): Cytogenetic investigation of leukemic and preleukemic disorders. Israel J Med Sci 15:500-506. 10. Mitelman F, Nilsson PG, Brandt L, Alimena G, Gastaldi R, Dallapiccola B (1981): Chromosome pattern, occupation, and clinical features in patients with acute nonlymphocytic leukemia. Cancer Genet Cytogenet 4:197-214. 11. Bernard P, Reiffers J, Lacombe F, Dachary D, Bavid B, Boisseau MR, Broustet A (1982): Prognostic value of age and bone marrow karyotype in 78 adults with myelogenous leukemia. Cancer Genet Cytogenet 7:153-163. 12. Brodeur GM, Williams DL, Kalwinsky DK, Williams KJ, Dahl GV (1983): Cytogenetic features of acute nonlymphoblastic leukemia in 78 children and adolescents. Cancer Genet Cytogenet 8:93-105. 13. McCarthy DM, Rassool FV, Goldman JM, Graham S, Birnie GD (1984): Genomic alterations involving the c-myc proto-oncogene locus during the evolution of a case of chronic granulocytic leukemia. Lancet ii:1362-1365.
ADDENDUM After c o m p l e t i o n of this c o m m u n i c a t i o n w e b e c a m e a w a r e of a report on a b n o r m a l ities of c h r o m o s o m e # 2 2 . In this report three cases w i t h an extra c h r o m o s o m e # 2 2 , all three w i t h M4 m o r p h o l o g y , are m e n t i o n e d (Fourth I n t e r n a t i o n a l W o r k s h o p on C h r o m o s o m e s in L e u k e m i a , 1982 (1984): A b n o r m a l i t i e s of c h r o m o s o m e 22. C a n c e r G e n e t Cytogent 11:316-318).