Sporadic Burkitt Lymphoma Research Articles

Chromosomal breakpoints and structural alterations of the c-myc locus differ in endemic and sporadic forms of Burkitt lymphoma.

We have examined the position of the chromosomal breakpoint relative to the human c-myc gene (MYC) and the presence of other structural alterations of the same locus in 19 fresh samples of Burkitt lymphoma (BL) and 13 BL-derived cell lines. This panel includes the two pathogenetic forms of BL: the endemic (African-type) BL (eBL) and sporadic (American-type) BL (sBL). In all cases tested, including fresh samples and cell lines, structural alterations of the 5' portion of the gene were detected, suggesting that they may be necessary for c-myc activation. However, the site of chromosomal breakpoint and the type of structural alterations differ in eBL and sBL. In 16 of 18 sBL cases, chromosomal translocation truncates the gene within a 5' region that includes the first intron, the first exon, and 5' flanking sequences. Conversely, in 14 of 14 eBL samples, the chromosomal breakpoint is located outside the c-myc locus, yet the same 5' sequences are affected by several mutations identifiable by restriction enzyme polymorphisms. Different genetic mechanisms may therefore be involved in chromosomal translocation/c-myc activation, and these differences may be a function of differences in the stage of differentiation of eBL versus sBL.

Epstein-Barr virus status and tumour cell phenotype in sporadic Burkitt's lymphoma.

Burkitt's lymphoma (BL) biopsy cells and derived cell lines can be grouped according to their patterns of reactivity with 6 selected monoclonal antibodies (MAbs) against B cell-associated surface antigens. Group I cells react only with MAbs J5 and 38.13, recognising the common acute lymphoblastic leukaemia antigen and a BL-associated antigen respectively; group II cells react with J5 and 38.13 and with one or more of a set of MAbs (Ki-24, MHM6, AC2, Ki-1) against "lymphoblastoid" antigens; group III cells react only with these anti-"lymphoblastoid" MAbs. Tumour biopsy cells from 17 cases of sporadic BL, 9 positive for the Epstein-Barr (EB) virus genome and 8 negative, have been analysed during the process of cell line establishment in vitro. In early passage the EB virus-negative BL cells showed either a group I phenotype or gave an additional reactivity with MAb Ki-24 which placed them in group II; these phenotypes remained essentially stable with continued growth of the cell lines for up to 50 passages. By contrast the EB virus-positive BL cells were much more susceptible to phenotypic change in vitro. Although such cells displayed a group I or group II phenotype in early passage, many of the lines soon moved into group III whilst retaining the karyotypic markers indicative of their malignant origin. These observations suggest that a resident EB virus genome can drive the in vitro progression of BL cells towards a more "lymphoblastoid" phenotype. This was confirmed in subsequent experiments where virus-negative BL cell lines were converted to EB virus positivity by in vitro infection. Clearly, therefore, phenotypic analysis of long-established lines can lead to false distinctions being drawn between the EB virus-positive and -negative forms of sporadic BL; both may derive from the same sub-population of target B cells in vivo.

Structure and expression of translocated c-myc oncogenes: specific differences in endemic, sporadic and AIDS-associated forms of Burkitt lymphomas.

Burkitt lymphomas (BL) are characterized by reciprocal chromosomal translocations which involve the c-myc oncogene locus on chromosome 8 and immunoglobulin (Ig) loci on either chromosome 2, 14 or 22 (Dalla-Favera et al. 1982, 1983; Taub et al. 1982; Leder et al. 1983; Croce et al. 1985). The consistent occurrence of these specific recombination events in BL and the presence of analogous recombinations involving c-myc in similar tumors in other species (Sheng-Ong 1982), suggests that the c-myc gene plays a role in the pathogenesis of BL. Despite their remarkable similarity at the cytogenetic level, these translocation events are extremely heterogeneous at the molecular level. In this study we report that chromosomal breakpoints and structural alterations of the c-myc locus differ in different subtypes of Burkitt lymphomas, namely endemic, sporadic BL and AIDS-associated undifferentiated B-cell lymphomas (AIDS-UBL). Chromosomal translocation is also associated with different levels of c-myc expression, and these levels directly correlate with the clonogenic and in vivo tumorigenic properties of BL cells.

Distinctions between endemic and sporadic forms of Epstein-Barr virus-positive Burkitt's lymphoma.

Tumour cell lines were established in vitro from 16 cases of Epstein-Barr (EB) virus genome-positive Burkitt's lymphoma (BL), 7 of "endemic" origin (i.e. from holoendemic malarial areas of Africa and of New Guinea) and 9 of "sporadic" origin (i.e. from outside such high-incidence areas). All the BL cell lines thus established were monoclonal by immunoglobulin isotype expression and displayed a characteristic chromosomal translocation, t(8:14) or t(8:22), confirming their malignant origin. Clear differences observed between the individual BL cell lines appeared to be related to their endemic or sporadic status. All 7 endemic cell lines began growth as a carpet of single cells, often with small, loose clumps appearing in later passage. Whilst 3 lines of sporadic origin displayed a similar pattern to the above, the majority of sporadic lines grew as large, tight clumps of cells from the first passage onwards. These differences in growth pattern were reflected by differences in cell surface phenotype, as defined in indirect immunofluorescence tests using a panel of monoclonal antibodies (MAbs) specific for B-lineage-associated antigens. BL cell lines could be classified into 3 separate groups on the basis of their reactivity with 6 particular antibodies (MHM6, AC2, Ki-1, Ki-24, J5 and 38.13). All 7 endemic BL cell lines and 2 of the 3 sporadic BL cell lines which began growth as single cells showed a group-I cell-surface phenotype (MHM6, AC2, Ki-1, Ki-24 negative; J5, 38.13 positive) in early passage. In contrast, all 6 sporadic BL cell lines which began growth in large clumps displayed a distinct group-II phenotype (MHM6, AC2, Ki-1 positive/negative; Ki-24, J5, 38.13 positive); in later passage most of these sporadic lines progressed to a group-III phenotype (MHM6, AC2, Ki-1, Ki-24 positive; J5, 38.13 negative) without loss of those immunoglobulin and chromosomal markers identifying the cells' malignant origin. These clear differences between endemic BL cell lines on the one hand and the majority of sporadic BL cell lines on the other suggest that endemic BL arises from a more restricted range of progenitor B cells than does the sporadic form of the disease.

Non-African sporadic Burkitt's lymphoma in Italian patients

A peculiar tumour of children, similar for certain histological and biological features to Burkitt's lymphoma has been recognized in Italy, probably a B lymphoma. the serological data are not consistent with the same aetiology of African cases, except for one of 8 patients ( 5 tested appropriately). “Maxicure with minitreatment” after cyclophosphamide has been reported for African cases; similar results have been achieved in 3 8 patients of this series with the adriamycin + vincristine combination; this combination probably deserves larger testing also in African cases. Four out of eight patients are faring well, at the time of reporting.