- Email: [email protected]
Variant translocation in Burkitt lymphoma
Variant Translocation in Burkitt Lymphoma H. Van Den Berghe, C. Parloir, S. Gosseye, V. Englebienne, G. Cornu, and G. Sokal
ABSTRACT: The demonstration of a t(2;8) (p12;q23) in a typical nonendemic Burkitt lymphoma (BL) in a European Caucasian child, provides evidence that variant translocations can be found in this type of malignancy as well as in other malignant hemopathies, particularly those with a Ph I chromosome. This observation is important when studying the significance of nonrandomly occurring chromosome anomalies in human malignancies. Thus it appears that in certain human hemopathies, e.g., chronic myelocytic leukemia and BL, the deletion of a specific chromosome, has. 22 and 8, respectively, may be the key karyotypic event associated with the disease, rather than the site of translocation of the deleted segments. INTRODUCTION Burkitt l y m p h o m a s (BL) have been s h o w n to present a n o n r a n d o m c h r o m o s o m e anomaly. M a n o l o v and Manolova [1] first demonstrated the presence of extra material on the long arm of c h r o m o s o m e 14 (14q+], a n d Zech et al. s h o w e d that this material originated from the long arm of c h r o m o s o m e 8 [2]. Since then several other investigators have confirmed these findings, and this reciprocal (8q;14q) translocation is a s s u m e d to be characteristic of African Burkitt l y m p h o m a . This article reports a case of typical Burkitt l y m p h o m a occurring in a European Caucasian child in w h i c h the t u m o r cells were characterized by a t(2p;8q) translocation. CLINICAL REPORT M.D., a female, was born January 1972 of socially p o o r l y a d a p t e d parents, of w h o m the mother was m e n t a l l y h a n d i c a p p e d . Little is k n o w n about the circumstances of birth and neonatal period, except that the birthweight was 3,250 g and that 5 weeks after birth surgical intervention was necessary for h y p e r t r o p h i c pyloric stenosis. P s y c h o m o t o r d e v e l o p m e n t was retarded: the child was able to sit w i t h o u t s u p p o r t at the age of 24 m o n t h s and w a l k e d alone at the age of 29 months. A t e n d e n c y to bruising and ecchymoses was noted after birth, but no special investigations were carried out until January 1975, w h e n at the age of 3 years, the child was found to have o n l y 40,000/ram ~ thrombocytes. The t h r o m b o p e n i a r e s p o n d e d favorably to p r e d n i s o n e treatment, but in June 1976 relapse occurred. On the basis of m a r k e d l y d i m i n i s h e d thrombocyte survival in the blood w i t h sequestration in the spleen, the diagnosis of chronic Werlhof disease was established, and s p l e n e c t o m y was perFrom the Division of Human Genetics, Department of Human Biology, University of Leuven, the Department of Pathology and Division of Hematology,Department of Internal Medicine, University of Louvain in Brussels. Address reprint requests to: Dr. H. Van Den Berghe, Academisch Ziekenhuis, Sint. Hafael, 3000 Leuven, Kapucijnenvoer 33, Leuven, Belgium. Received November 29, 1978; accepted January 29, 1979.
~) Elsevier North Holland, Inc., 1979 Cancer Genetics and Cytogenetics 1, 9-14 (1979) 0165-4608/79/01000906502.25
10
H. Van Den Berghe et al. formed on the 24th of September 1976. A few days after surgery the thrombocyte count reached 472,000/mm 3 and the child was discharged on September 30, 1976, in good condition and with perfectly normal values for all hematological investigations. She was readmitted October 21, 1976, because of anorexia and vomiting. There were no other specific complaints. The body temperature was normal, clinical investigation was normal, except for a subcutaneous tumor 3 cm in diameter, 1.5 cm high, which could be felt in the right temporal region. Within a few days, a facial asymmetry became apparent, due to swelling of the maxilla on the left side, and some enlarged lymph nodes could be felt in the cervical regions. Radiologically a large osteolytic zone was found in the left maxilla and a more discrete one in the skull, corresponding to the palpable temporal tumor. A skeletal survey, as well as an isotope scan, failed to show other detectable lesions. On intravenous pyelography, however, both kidneys were found to be considerably enlarged. Cytological investigation of a lymph node and of the temporal tumor showed anaplastic immunoblastosarcomatous cells. Biopsy of a cervical ganglion showed a lymph node with the gross architecture still preserved, but with several areas of abnormal cell proliferation consisting of large, regularly shaped round basophilic cells with scanty cytoplasm, numerous mitotic figures, and abundant phagocytosing macrocytes; thus presenting a "starry sky" picture characteristic for Burkitt lymphoma (Figures 1 and 2). The tumor in the temporal region showed the same features, with the abnormal cells invading the striated muscle. In the bone marrow, the same abnormal cell population and intense macrophage activity were found. A sphenoidal cleft syndrome with paresis of cranial nerves IV, V, VI, and VII was soon to appear, due to complete destruction of the left maxillary sinus. The tumor was found to invade the nasal cavity, the ethmoidal and the right maxillary sinuses, and the subcutaneous tissue of the cheek. Three weeks after admission, Figure 1 Lymph node biopsy. Abnormal proliferation of closely packed monomorphic cells with scant cytoplasm and round medium-sized nucleus with one to several conspicuous nucleoli. "Starry sky" pattern due to the presence of numerous scattered phagocytes (Hand E,
x20o).
Variant Translocation in Burkitt Lymphoma
Figure 2
11
Lymph node biopsy. Higher magnification (X800) to show cytological details.
tumor cells were also found in the cerebrospinal fluid. EBV antibodies were 1/1024 on September 10, 1/512 on November 17, and 1/256 on December 8. She was transferred to a sterile unit and chemotherapy was started with asparaginase, prednisone, vincristin, and rubidomycin for 3 weeks. The tumoral masses disappeared very quickly, and on the 15th day of treatment the bone marrow was found to be free of tumor ceils. Asparaginase had to be stopped on day 17 because of uncontrollable vomiting, a salt-loosing nephritis appeared and necessitated the administration of 5 liters of physiological solutions per day; despite the fact that the renal masses disappeared, arterial hypertension persisted for quite some time. Further treatment consisted of cyclophosphamide and methotrexate for 6 days, followed by radiotherapy (2000 rads to the skull, 1000 rads to the spine) and intrathecal injection of methotrexate. At the end of this treatment, signs of cerebro-meningeal involvement as well as the facial tumoral masses disappeared; with the exception of the facial nerve, the other cranial nerves had only partially recovered. The child was discharged January 21, 1977, on a weekly therapy of 300 mg cyclophosphamide. On the 1st of February the bone marrow was normal, the WBC count was 1500/mm 3, with some 10% immunoblasts (Burkitt cells] in the buffy-coat. From February 10 on, reinduction of chemotherapy was performed, consisting of prednisone, rubidomycin, vincristin, and asparaginase, to be followed by a weekly injection of 250 mg cyclophosphamide. The child, however, had to be readmitted in February because of vomiting, rise of temperature, palpebral edema, left exophthalmus and ptosis of the right eyelid, and severe pain in the head and neck. The cerebrospinal fluid showed numerous sarcomatous elements with abundant mitoses; methotrexate was injected intrathecally and cyclophosphamide intravenously. Six days later, the abnormal elements had disappeared, but a pancytopenia, not explained by the chemotherapy and suggesting bone marrow relapse, was found. It was then decided to stop the antitumor treatment and to treat the child symptomatically. She died on April 4, 1977, 51/2 months after the first symptoms had appeared.
12
H. Van Den Berghe et al.
CYTOGENETIC INVESTIGATIONS Two different tissue s a m p l e s were m a d e available for cytogenetic investigation. One was from the spleen, removed on the 24th of September; the other was a l y m p h node b i o p s y performed on the 29th of October, before a n t i t u m o r treatment had started. Cultures were set up in MEM s u p p l e m e n t e d w i t h 30% p o o l e d h u m a n serum, glutam i n e 0.75 mg %, and p e n i c i l l i n 1000 U / m m 3. Standard air-dried c h r o m o s o m e preparations were m a d e a n d processed for R b a n d i n g (acridine-orange). The results of these studies are s u m m a r i z e d in Table 1. The karyotype of the s p l e e n cells grown with, as well as without, p h y t o h e m a g g l u t i n i n (PHA) was normal. The karyotype of the l y m p h node cells, however, was consistently abnormal in 14 out of 15 metaphases. One m e t a p h a s e was normal, and cells with 44 and 45 c h r o m o s o m e s s h o w e d r a n d o m c h r o m o s o m e loss. The c h r o m o s o m e a b n o r m a l i t y in the abnormal cells was a reciprocal translocation b e t w e e n segments of the short arm of c h r o m o s o m e 2 and of the long arm of c h r o m o s o m e 8, w i t h the breakpoints being in 2p12 and 8q23, respectively [karyotype:t(2;8)(p12;q23)] (Figure 3).
DISCUSSION There can be no doubt about the nature of the malignant t u m o r w h i c h was present in the patient described. The clinical a p p e a r a n c e w i t h m a x i l l a r y and other tumors in the head and neck regions, plus the typical histological picture and positive EBV serological reaction all p o i n t to Burkitt l y m p h o m a . Moreover, a consistent chromosome a n o m a l y involving a break in or near b a n d q23 or 24 of c h r o m o s o m e 8, pres u m e d to be characteristic of Burkitt l y m p h o m a , was found in the malignant cells. In contrast w i t h other Burkitt tumors, however, the other c h r o m o s o m e i n v o l v e d in the rearrangement was not a 14, but a reciprocal translocation with the short arm of c h r o m o s o m e 2 [t(2;8)(p12;q23)]. The relevance of this observation becomes a p p a r e n t w h e n one considers variants of n o n r a n d o m l y occurring translocations, involving two or more c h r o m o s o m e s in other m a l i g n a n t hemopathies. In chronic myelocytic leukemia, up to 10% of the cases m a y show a translocation of the 22q deleted material on a c h r o m o s o m e different from 9 [3]. In one subtype of acute m y e l o g e n o u s leukemia, material of the long arm of c h r o m o s o m e 8 was found on the long arm of a c h r o m o s o m e 21 (Karyotype: [t(8;21) (q22;q22)] [4,5]. In one instance, however, this 8q deleted material was found not on a 21, but on a 1 c h r o m o s o m e [6]; in two other instances a third c h r o m o s o m e participated in the rearrangement [7]. No variant translocation has thus far been described for the t(15;17)(q26;q22) rearrangement in acute p r o m y e l o c y t i c leukemia [8,9], but the n u m b e r of cases so far k n o w n to present the translocation is only about 20. The present article describes the first e x a m p l e of a variant translocation in BL. Evidence is, thus, a c c u m u l a t i n g that these u n u s u a l translocations m a y exist for all so-called characteristic c h r o m o s o m e rearrangements. In Ph I positive CML, in the Table 1
Results of the cytogenetic investigations
Date 24 SEP 1976
29 OCT 1976
Tissue and culture type Spleen 24 hr without PHA Spleen 72 hr with PHA Lymph node 48 hr without PHA
Chromosome count No. 44 45 46 47
Karyotype
20
-
46, XX, normal
-
1
9
-
46, XX, normal
2
3
10
-
46, XX, t(2;8){p12;q23) 93.4% 46, XX, normal 6.6%
Figure 3
Karyotype of the lymph node (R banding, acridine-orange). Reciprocal translocation between chromosomes 2 and 8 t(2;8)(p12;q23).
O
14
H. Van Den Berghe et al.
above-mentioned subtype of AML, and in BL, the structural changes in the 22q and the 8q are the only consistent ones. This is an important observation for the study of the significance of n o n r a n d o m l y occurring chromosome changes in h u m a n malignant hemopathies. In addition, another noteworthy observation was made in the present case. Whereas with regard to the t(9;22) and t(8;21) there is still some doubt about these rearrangements being true reciprocal translocations, since the chromosome segments involved are small a n d because of the limiting resolution of the presently available techniques, the t(2;8) rearrangement in the present case is very clearly a reciprocal translocation. Finally, it should be emphasized that this variant translocation was found in a n o n e n d e m i c BL; it is possible indeed that variant translocations may not be present in e n d e m i c BL. Supported in part by the Belgian Cancer Fund (A.S.L.K.).
REFERENCES 1. Manolov G, Manolova Y (1972): Marker band in one chromosome 14 from Burkitt lymphomas. Nature (Lond.) 237, 33-34. 2. Zech L. Haglund U, Nilsson K, Klein G (1976): Characteristic chromosome abnormalities in biopsies and lymphoid-cell lines from patients with Burkitt and non-Burkitt lymphomas. Int J Cancer 17, 47-56. 3. Sonta SI, Sandberg AA (1977): Chromosomes and causation of human cancer and leukemia. XXIV. Unusual and complex Ph ~ translocations and their clinical significance. Blood 50, 691-697. 4. Rowley J (1973): Identification of a translocation with quinacrine fluorescence in a patient with acute leukemia. Ann Genet 16, 109-112. 5. Sakurai M, Oshimura M, Kakati S, Sandberg AA (1974): 8-21 translocation and missing sex chromosomes in acute leukemia. Lancet 2, 227-228. 6. Van Den Berghe H, David G, Michaux JL, Sokal G (1976): Nonrandom chromosome anomalies in human myeloproliferative disorders. Abstr. 3rd Int. Symp. Detection and Prevention of Cancer. New York, April 26-May 1. 7. Lindgren V, Rowley JD (1977): Comparable complex rearrangements involving 8;21 and 9;22 translocations in leukemia. Nature 266, 744-745. 8. Rowley JD, Golomb HM, Dougherty C (1977): 15/17 translocation, a consistent chromosomal change in acute promyelocytic leukemia. Lancet 1, 549-550. 9. Van Den Berghe H, Louwagie A, Broeckaert-Van Orshoven A, David G, Verwilghen R, Michaux JL, Sokal G. Chromosome abnormalities in acute promyelocytic leukemia (APL). Cancer, in press.
ABSTRACT: The demonstration of a t(2;8) (p12;q23) in a typical nonendemic Burkitt lymphoma (BL) in a European Caucasian child, provides evidence that variant translocations can be found in this type of malignancy as well as in other malignant hemopathies, particularly those with a Ph I chromosome. This observation is important when studying the significance of nonrandomly occurring chromosome anomalies in human malignancies. Thus it appears that in certain human hemopathies, e.g., chronic myelocytic leukemia and BL, the deletion of a specific chromosome, has. 22 and 8, respectively, may be the key karyotypic event associated with the disease, rather than the site of translocation of the deleted segments. INTRODUCTION Burkitt l y m p h o m a s (BL) have been s h o w n to present a n o n r a n d o m c h r o m o s o m e anomaly. M a n o l o v and Manolova [1] first demonstrated the presence of extra material on the long arm of c h r o m o s o m e 14 (14q+], a n d Zech et al. s h o w e d that this material originated from the long arm of c h r o m o s o m e 8 [2]. Since then several other investigators have confirmed these findings, and this reciprocal (8q;14q) translocation is a s s u m e d to be characteristic of African Burkitt l y m p h o m a . This article reports a case of typical Burkitt l y m p h o m a occurring in a European Caucasian child in w h i c h the t u m o r cells were characterized by a t(2p;8q) translocation. CLINICAL REPORT M.D., a female, was born January 1972 of socially p o o r l y a d a p t e d parents, of w h o m the mother was m e n t a l l y h a n d i c a p p e d . Little is k n o w n about the circumstances of birth and neonatal period, except that the birthweight was 3,250 g and that 5 weeks after birth surgical intervention was necessary for h y p e r t r o p h i c pyloric stenosis. P s y c h o m o t o r d e v e l o p m e n t was retarded: the child was able to sit w i t h o u t s u p p o r t at the age of 24 m o n t h s and w a l k e d alone at the age of 29 months. A t e n d e n c y to bruising and ecchymoses was noted after birth, but no special investigations were carried out until January 1975, w h e n at the age of 3 years, the child was found to have o n l y 40,000/ram ~ thrombocytes. The t h r o m b o p e n i a r e s p o n d e d favorably to p r e d n i s o n e treatment, but in June 1976 relapse occurred. On the basis of m a r k e d l y d i m i n i s h e d thrombocyte survival in the blood w i t h sequestration in the spleen, the diagnosis of chronic Werlhof disease was established, and s p l e n e c t o m y was perFrom the Division of Human Genetics, Department of Human Biology, University of Leuven, the Department of Pathology and Division of Hematology,Department of Internal Medicine, University of Louvain in Brussels. Address reprint requests to: Dr. H. Van Den Berghe, Academisch Ziekenhuis, Sint. Hafael, 3000 Leuven, Kapucijnenvoer 33, Leuven, Belgium. Received November 29, 1978; accepted January 29, 1979.
~) Elsevier North Holland, Inc., 1979 Cancer Genetics and Cytogenetics 1, 9-14 (1979) 0165-4608/79/01000906502.25
10
H. Van Den Berghe et al. formed on the 24th of September 1976. A few days after surgery the thrombocyte count reached 472,000/mm 3 and the child was discharged on September 30, 1976, in good condition and with perfectly normal values for all hematological investigations. She was readmitted October 21, 1976, because of anorexia and vomiting. There were no other specific complaints. The body temperature was normal, clinical investigation was normal, except for a subcutaneous tumor 3 cm in diameter, 1.5 cm high, which could be felt in the right temporal region. Within a few days, a facial asymmetry became apparent, due to swelling of the maxilla on the left side, and some enlarged lymph nodes could be felt in the cervical regions. Radiologically a large osteolytic zone was found in the left maxilla and a more discrete one in the skull, corresponding to the palpable temporal tumor. A skeletal survey, as well as an isotope scan, failed to show other detectable lesions. On intravenous pyelography, however, both kidneys were found to be considerably enlarged. Cytological investigation of a lymph node and of the temporal tumor showed anaplastic immunoblastosarcomatous cells. Biopsy of a cervical ganglion showed a lymph node with the gross architecture still preserved, but with several areas of abnormal cell proliferation consisting of large, regularly shaped round basophilic cells with scanty cytoplasm, numerous mitotic figures, and abundant phagocytosing macrocytes; thus presenting a "starry sky" picture characteristic for Burkitt lymphoma (Figures 1 and 2). The tumor in the temporal region showed the same features, with the abnormal cells invading the striated muscle. In the bone marrow, the same abnormal cell population and intense macrophage activity were found. A sphenoidal cleft syndrome with paresis of cranial nerves IV, V, VI, and VII was soon to appear, due to complete destruction of the left maxillary sinus. The tumor was found to invade the nasal cavity, the ethmoidal and the right maxillary sinuses, and the subcutaneous tissue of the cheek. Three weeks after admission, Figure 1 Lymph node biopsy. Abnormal proliferation of closely packed monomorphic cells with scant cytoplasm and round medium-sized nucleus with one to several conspicuous nucleoli. "Starry sky" pattern due to the presence of numerous scattered phagocytes (Hand E,
x20o).
Variant Translocation in Burkitt Lymphoma
Figure 2
11
Lymph node biopsy. Higher magnification (X800) to show cytological details.
tumor cells were also found in the cerebrospinal fluid. EBV antibodies were 1/1024 on September 10, 1/512 on November 17, and 1/256 on December 8. She was transferred to a sterile unit and chemotherapy was started with asparaginase, prednisone, vincristin, and rubidomycin for 3 weeks. The tumoral masses disappeared very quickly, and on the 15th day of treatment the bone marrow was found to be free of tumor ceils. Asparaginase had to be stopped on day 17 because of uncontrollable vomiting, a salt-loosing nephritis appeared and necessitated the administration of 5 liters of physiological solutions per day; despite the fact that the renal masses disappeared, arterial hypertension persisted for quite some time. Further treatment consisted of cyclophosphamide and methotrexate for 6 days, followed by radiotherapy (2000 rads to the skull, 1000 rads to the spine) and intrathecal injection of methotrexate. At the end of this treatment, signs of cerebro-meningeal involvement as well as the facial tumoral masses disappeared; with the exception of the facial nerve, the other cranial nerves had only partially recovered. The child was discharged January 21, 1977, on a weekly therapy of 300 mg cyclophosphamide. On the 1st of February the bone marrow was normal, the WBC count was 1500/mm 3, with some 10% immunoblasts (Burkitt cells] in the buffy-coat. From February 10 on, reinduction of chemotherapy was performed, consisting of prednisone, rubidomycin, vincristin, and asparaginase, to be followed by a weekly injection of 250 mg cyclophosphamide. The child, however, had to be readmitted in February because of vomiting, rise of temperature, palpebral edema, left exophthalmus and ptosis of the right eyelid, and severe pain in the head and neck. The cerebrospinal fluid showed numerous sarcomatous elements with abundant mitoses; methotrexate was injected intrathecally and cyclophosphamide intravenously. Six days later, the abnormal elements had disappeared, but a pancytopenia, not explained by the chemotherapy and suggesting bone marrow relapse, was found. It was then decided to stop the antitumor treatment and to treat the child symptomatically. She died on April 4, 1977, 51/2 months after the first symptoms had appeared.
12
H. Van Den Berghe et al.
CYTOGENETIC INVESTIGATIONS Two different tissue s a m p l e s were m a d e available for cytogenetic investigation. One was from the spleen, removed on the 24th of September; the other was a l y m p h node b i o p s y performed on the 29th of October, before a n t i t u m o r treatment had started. Cultures were set up in MEM s u p p l e m e n t e d w i t h 30% p o o l e d h u m a n serum, glutam i n e 0.75 mg %, and p e n i c i l l i n 1000 U / m m 3. Standard air-dried c h r o m o s o m e preparations were m a d e a n d processed for R b a n d i n g (acridine-orange). The results of these studies are s u m m a r i z e d in Table 1. The karyotype of the s p l e e n cells grown with, as well as without, p h y t o h e m a g g l u t i n i n (PHA) was normal. The karyotype of the l y m p h node cells, however, was consistently abnormal in 14 out of 15 metaphases. One m e t a p h a s e was normal, and cells with 44 and 45 c h r o m o s o m e s s h o w e d r a n d o m c h r o m o s o m e loss. The c h r o m o s o m e a b n o r m a l i t y in the abnormal cells was a reciprocal translocation b e t w e e n segments of the short arm of c h r o m o s o m e 2 and of the long arm of c h r o m o s o m e 8, w i t h the breakpoints being in 2p12 and 8q23, respectively [karyotype:t(2;8)(p12;q23)] (Figure 3).
DISCUSSION There can be no doubt about the nature of the malignant t u m o r w h i c h was present in the patient described. The clinical a p p e a r a n c e w i t h m a x i l l a r y and other tumors in the head and neck regions, plus the typical histological picture and positive EBV serological reaction all p o i n t to Burkitt l y m p h o m a . Moreover, a consistent chromosome a n o m a l y involving a break in or near b a n d q23 or 24 of c h r o m o s o m e 8, pres u m e d to be characteristic of Burkitt l y m p h o m a , was found in the malignant cells. In contrast w i t h other Burkitt tumors, however, the other c h r o m o s o m e i n v o l v e d in the rearrangement was not a 14, but a reciprocal translocation with the short arm of c h r o m o s o m e 2 [t(2;8)(p12;q23)]. The relevance of this observation becomes a p p a r e n t w h e n one considers variants of n o n r a n d o m l y occurring translocations, involving two or more c h r o m o s o m e s in other m a l i g n a n t hemopathies. In chronic myelocytic leukemia, up to 10% of the cases m a y show a translocation of the 22q deleted material on a c h r o m o s o m e different from 9 [3]. In one subtype of acute m y e l o g e n o u s leukemia, material of the long arm of c h r o m o s o m e 8 was found on the long arm of a c h r o m o s o m e 21 (Karyotype: [t(8;21) (q22;q22)] [4,5]. In one instance, however, this 8q deleted material was found not on a 21, but on a 1 c h r o m o s o m e [6]; in two other instances a third c h r o m o s o m e participated in the rearrangement [7]. No variant translocation has thus far been described for the t(15;17)(q26;q22) rearrangement in acute p r o m y e l o c y t i c leukemia [8,9], but the n u m b e r of cases so far k n o w n to present the translocation is only about 20. The present article describes the first e x a m p l e of a variant translocation in BL. Evidence is, thus, a c c u m u l a t i n g that these u n u s u a l translocations m a y exist for all so-called characteristic c h r o m o s o m e rearrangements. In Ph I positive CML, in the Table 1
Results of the cytogenetic investigations
Date 24 SEP 1976
29 OCT 1976
Tissue and culture type Spleen 24 hr without PHA Spleen 72 hr with PHA Lymph node 48 hr without PHA
Chromosome count No. 44 45 46 47
Karyotype
20
-
46, XX, normal
-
1
9
-
46, XX, normal
2
3
10
-
46, XX, t(2;8){p12;q23) 93.4% 46, XX, normal 6.6%
Figure 3
Karyotype of the lymph node (R banding, acridine-orange). Reciprocal translocation between chromosomes 2 and 8 t(2;8)(p12;q23).
O
14
H. Van Den Berghe et al.
above-mentioned subtype of AML, and in BL, the structural changes in the 22q and the 8q are the only consistent ones. This is an important observation for the study of the significance of n o n r a n d o m l y occurring chromosome changes in h u m a n malignant hemopathies. In addition, another noteworthy observation was made in the present case. Whereas with regard to the t(9;22) and t(8;21) there is still some doubt about these rearrangements being true reciprocal translocations, since the chromosome segments involved are small a n d because of the limiting resolution of the presently available techniques, the t(2;8) rearrangement in the present case is very clearly a reciprocal translocation. Finally, it should be emphasized that this variant translocation was found in a n o n e n d e m i c BL; it is possible indeed that variant translocations may not be present in e n d e m i c BL. Supported in part by the Belgian Cancer Fund (A.S.L.K.).
REFERENCES 1. Manolov G, Manolova Y (1972): Marker band in one chromosome 14 from Burkitt lymphomas. Nature (Lond.) 237, 33-34. 2. Zech L. Haglund U, Nilsson K, Klein G (1976): Characteristic chromosome abnormalities in biopsies and lymphoid-cell lines from patients with Burkitt and non-Burkitt lymphomas. Int J Cancer 17, 47-56. 3. Sonta SI, Sandberg AA (1977): Chromosomes and causation of human cancer and leukemia. XXIV. Unusual and complex Ph ~ translocations and their clinical significance. Blood 50, 691-697. 4. Rowley J (1973): Identification of a translocation with quinacrine fluorescence in a patient with acute leukemia. Ann Genet 16, 109-112. 5. Sakurai M, Oshimura M, Kakati S, Sandberg AA (1974): 8-21 translocation and missing sex chromosomes in acute leukemia. Lancet 2, 227-228. 6. Van Den Berghe H, David G, Michaux JL, Sokal G (1976): Nonrandom chromosome anomalies in human myeloproliferative disorders. Abstr. 3rd Int. Symp. Detection and Prevention of Cancer. New York, April 26-May 1. 7. Lindgren V, Rowley JD (1977): Comparable complex rearrangements involving 8;21 and 9;22 translocations in leukemia. Nature 266, 744-745. 8. Rowley JD, Golomb HM, Dougherty C (1977): 15/17 translocation, a consistent chromosomal change in acute promyelocytic leukemia. Lancet 1, 549-550. 9. Van Den Berghe H, Louwagie A, Broeckaert-Van Orshoven A, David G, Verwilghen R, Michaux JL, Sokal G. Chromosome abnormalities in acute promyelocytic leukemia (APL). Cancer, in press.