BrifirhJournal of Haematology, 1979,43,87-90.

t(8;14) Translocation in a Burkitt’s Type of Lymphoblastic Leukaemia (L3)

R. BERGER, A. BERNHEIM, J. c . BROUET,* M. T. DANIELt AND G. FLANDRINt

Laboratoire de Cytoge‘ne‘tique, Institut de Recherches sur les Leuce‘mies et les Maladies du Sang, Hdpital Saint-Louis, Paris,* Unite‘ d’lmmunochimie et d’lmmunopathologie, U108 INSERM,

Hdp ita 1 Saint- Lo u is, Par is , and t La bo rat0 ire d’ He‘ma t o log ie , Hdpita 1 Saint- Lo u is, Paris , France

(Received 10 January 1979; accepted for publication 23 January 1979)

SUMMARY. Cytogenetic findings on five patients with ALL Burkitt’s type are reported. A t(8; 14) (q23;q32) translocation identical to that found in Burkitt’s lymphoma cells was found in each case. The relationship between ALL, L3 type and Burkitt’s tumours is discussed.

In their report on six cases of acute lymphoblastic leukaemia (ALL) associated Burkitt’s tumour, Flandrin et a1 (1975) stressed the possibility of a true leukaemic presentation of Burkitt’s lymphoma. We have carried out chromosome analysis on five new cases of Burkitt type ALL (L3, following the FAB classification; Bennett et a l , 1976), in order to find out whether the t(8; 14) translocation consistently found in Burkitt’s tumour cells (Zech et all 1976) is also present in the Burkitt type ALL.

MATERIAL AND METHODS

Patients. The main clinical and haematological data for the five patients is summarized in Table I. All were Caucasians and none lived in an area endemic for Burkitt’s lymphoma. Four were children whilst one was a 76-year-old man. In four cases the leukaemia was found a t the same time as the tumour (testicular in case 2; retrotonsillar in cases 3 and 4, and colic in case 5). A brother of patient 3 died from a cavum adenocarcinoma.

Cytological studies. Cytological studies were performed on May-Grunwald-Giemsa (MGG) stained bone marrow and peripheral blood cells. The following cytochemical reactions were tested in all patients: peroxidase, oil red 0, acid phosphatase.

Lymphocyte surface markers. Membrane-bound immunoglobulins (SIg) were studied by direct immunofluorescence on blast cells obtained from bone marrow aspirates and defi- brinated blood using sera monospecific for the p, y, a, K and 1 chains (Preud’homme & Seligmann, 1972).

Cytogenetics. Chromosome studies were performed on bone marrow cells following 1 h incubation with colchicine and from 24,48 and/or 72 h non-stimulated and 72 h PHA-stimu- lated blood cell cultures. Standard Giemsa banding techniques, GTG- (G bands using trypsin

Maladies du Sang, HBpital Saint-Louis, 2 place du Dr Fournier, 75475, Paris Cedex 10. Correspondence: Dr R. Berger, Laboratoire de CytogPnPtique, Institut de Recherches sur les LeucPmies et les

0007-1048/79/090ooo87$02.00 0 1979 Blackwell Scientific Publications

87

88 R. Berger et al

and Giemsa), RHG- (R-bands using heating and Giemsa) and CBG- (C-bands using barium hydroxide and Giemsa) were used.

RESULTS

Morphologic Studies (Fig 1) In each case, bone marrow aspiration showed a massive infiltration (> 90%) by the tumour

cells. The blast cells varied slightly in size (20-25 pm in diameter) but were otherwise identical. The cytoplasms were uniformly and intensely deeply basophilic without granules. Most cells contained empty cytoplasmic vacuoles (1-2 pm in diameter) on the MGG smears. The nuclei were round and large with a finely clumped chromatin. Many mitotic figures were observed. The blast cells showed a marked cytoplasmic basophilia. They were usually devoid of PAS-positive material. Coarse lipid droplets were demonstrated in the cytoplasmic vacuoles by oil red 0 staining. The acid phosphatase reaction was negative or weakly positive. The peroxidase reaction was negative. Some macrophages with light cytoplasmic matrix and cell debris were observed. Acid phosphatase activity was very strong in these macrophages.

Lymphocyte Surface Membrane Markers The presence of monoclonal membrane immunoglobulins indicated a B cell origin for the

blast cells in four of the five cases (Table I). In case 4 a complete typing was impossible for technical reasons.

Cytogenetics The majority of the mitoses of each patient contained 46 chromosomes (Table 11). A t(8;14)

(q23;32) translocation (Fig 2) was present in some of the cells of all the patients, but normal karyotypes were also observed from bone marrow and unstimulated blood cells of patients

A rearrangement of chromosome No. 1 ( lq+) was present in addition to the t(814) in some of the cells of patient 3, bearing the translocation. A 13q+ was found in 4/52 cells examined of patient 4. Chromosome analysis for case 5 was very difficult, partly due to the quality of the preparations, partly due to the existence of multiple rearrangements, varying from cell to cell. A typical t(8;14) translocation was present in a minority of mitoses, the other ones having as common anomalies a Dq+ chromosome possibly resulting from a rearrangement involving chromosomes No. 13 and 1, an extra metacentric chromosome of the same size as a No. 16 but lacking C-band heterochromatin and an extra small metacentric chromosome.

1-4.

DISCUSSION

A Burkitt type of ALL has been described, the diagnosis being based on the cytological appearance of blast cells resembling Burkitt’s lymphoma cells and monoclonal B-cell origin for the blasts. In our experience the incidence of this variety of ALL can be estimated as being 1-2% of ALL and occurring more frequently in children than in adults.

The finding of a t(8;14) translocation is important in any discussion of the relationships existing between ALL, L3 type and Burkitt’s lymphoma. Recent cytogenetic studies have

Ruvkitt Type ALL

FIG 1. Bone inarrow smear (May-Grunwald-Giemsa) x 100. The blast cells arelarge and homogenous. The cytoplasm is intensely basophilic with prominent vacuolation.

(Facing p. 88)

R. Betger et a1

FIG 2. Partial karyotypes: t(8;14) translocation. R-bands (cases 1 and 4); G-bands (cases 2, 3 and 5).

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shown that a t(8;14) translocation is present in Burkitt’s tumour cells (Zech et al , 1976). This rearrangement has been considered as possibly being specific for Burkitt’s lymphoma cells.

A chromosome 14q+ has been found in other lymphomas but generally the extra material on the long arm of chromosome No. 14 is not derived from chromosome No. 8 (review in Berger et a l , 1979). Similarly a few cases of ALL having blasts of B-cell origin and possessing 14q+ chromosome, but without the t(8;14) translocations have been reported (Oshimura et a l , 1977; Cimino, 1978). Two cases of chronic lymphocytic leukaemia having a t(8; 14) transloca- tion were reported by Fleischman & Prigogina (1978) but no details of the clinical features of the diseases were given.

The above reported findings suggest that ALL, L3 and Burkitt’s lymphoma are different varieties of the same disease, the involvement of bone marrow being frequent in the so-called ‘non African’ Burkitt’s lymphoma patients (Cohen et a l , 1969) such as in case 4. Cytological, immunological and cytogenetic similarities indicate that aetiological factors common to ALL, L3 type and Burkitt’s lymphoma are involved in all varieties of the disease.

Note added inprooj Since the preparation of this paper, a sixth case of ALL Burkitt’s type has been studied. The identical t(8;14) translocation was found.

ACKNOWLEDGMENTS

We thank Dr Schlegel for referring patient 4, and Mrs M. Leconiat and Miss D. Vecchione for their excellent technical assistance.

REFERENCES

BENNFIT, J.M., CATOVSKY, D., DANIEL, M.T., FLAN- DRIN, G., GALTON, D.A.G., GRALNICK, H.R. & SUL- TAN, c . (1976) Proposals for the classification of the acute leukaemias. BritishJournal offfaematology, 33,

BERGER, R., BERNHEIM, A., FELLOUS, M. & BROUET, J.C. (1979) Cytogenetic study of a European Bur- kitt’s lymphoma cell line. Journal of the National Cancer Institute (in press).

CIMINO, M.C., ROTH, D.G., GOLOMB, H.M. & Row- LEY, J.D. (1978) A chromosome marker for B-cell cancers. New Englandjournal ofhfedicine, 298,1422.

COHEN, M.H., BENNFIT, J.M., BERARD, C.W., ZIEGLER, J.L., VOGEL, C.L., SHEAGREN, J.N. & CAR- BONE, P.P. (1969) Burkitt’s tumor in the United States. Cancer, 23, 1259-1272.

FLANDRIN, G., BROUET, J.C., DANIEL, M.T. & PREUD’- HOMME, J.L. (1975) Acute leukemia with Burkitt’s tumor cells: a study of six cases with special refer-

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FLEISCHMAN, E.W. & PRIGOGINA, E.L. (1978) Karyo- type peculiarities of malignant lymphomas. Human Genetics, 35, 269-279.

OSHIMURA, M., FREEMAN, A.I. & SANDBERG, A.A. (1977) Chromosomes and causation of human cancer and leukemia. XXVI. Banding studies in acute lymphoblastic leukemia (ALL). Cancer, 40,

PREUD’HOMME, J.L. & SELIG~IANN, M. (1972) Im- munoglobulins on the surface of lymphoid cells in Waldenstrom’s macroglobulinemia. Journal of Clinical Investigation, 51, 701-705.

ZECH, L., HAGLUND, U., NILSSON, K. & KLEIN, G. (1976) Characteristic chromosomal abnormalities in biopsies and lymphoid-cell lines from patients with Burkitt and non-Burkitt lymphomas. Interna- rionaljournal of Cancer, 17,4556.

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