Burkitt's lymphoma (BL)

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Burkitt's lymphoma (BL)

Clinics and Pathology

Phenotype / cell stem origin Pan-B antigens positive; TdT-, CD10+; CD5-; sIgM+. The cell of origin is a peripheral IgM+ memory B-cell (presence of somatic hypermutation of the Ig gene)

Epidemiology Most common in children (1/3 of lymphomas). In adult it accounts for 3-4% of all lymphomas in western countries and it is frequently associated with immunodeficiency

Clinics
There is an endemic variant, affecting africans, which primarily involves the jaws and other facial bones.
The non-endemic variant may be associated with immunodeficiency states and usually presents with abdominal involvement (distal ileum, ciecum, mesentery). The disease is very aggressive and requires prompt treatment with appropriate regimens.

Cytology The blast cells in the peripheral blood and bone marrow display a basophilic cytoplasm with characteristic vacuolization, a picture indisinguishable from acute lymphoblastic leukemia (ALL) L3 of the FAB classification, which represents the leukemic counterpart of BL.

Pathology
The lymphoma consists of a monomorphic infiltrate of the lymph node by medium-sized cells showing round nuclei with several nucleoli and basophilic cytoplasm. Numerous benign macrophages confer a histologic pattern referred to as ³starry sky². Involvement of the peripheral blood and bone marrow may occur.
The related form ³Burkitt-like² lymphoma shows intermediate features between diffuse large cell lymphoma and BL and probably includes different disease entities. It was suggested by the WHO panel that only those cases with c-MYC rearrangement and/or a >99% proliferation fraction as demonstrated by Ki-67 positivity should be classified as Burkitt-like lymphoma

Treatment Aggressive regimens specifically designed for this lymphoma must be used

Evolution Very rapid if untreated. Patients with limited disease and favourable prognostic features at presentation may rapidly show disease dissemination

Prognosis If treated promptly with appropriate regimens the majority of patients can be cured

Cytogenetics

Cytogenetics Morphological
The primary chromosome anomaly is the translocation t(8;14)(q24;q32), found in 60-70% of the cases. Variant translocations having in common an 8q24 break, i.e the t(8;22)(q24;q11) and t(2;8)(p12;q24) occur in approximately 10-15% and 2-5% of the cases, respectively. A minority of cases may carry a duplication of chromosome 1, involving the 1q21-25 segment as the only detectable chromosome lesion
In the Burkitt-like form there are at least 3 cytogenetic categories: one with an 8q24/c-MYC translocation, one with an 8q24 and 18q21/ BCL2 translocation and another with ³miscellaneous² rearrangements, frequently including an 18q21 break

Probes
Conventional karyotyping is the method of choice for the detection of the 8q24 translocations occurring in BL.
There is variability in the location of the breakpoint at band 8q24, making the detection of c-MYC rearrangement (see below) difficult by molecular genetics. Southern blotting is the preferred method. In the endemic form the breakpoint in the Ig locus is usually located in the Ig heavy chain variable region, whereas in the nonendemic form the breakpoint falls in the Ig switch region.
Fluorescence in situ hybridization is of value in detecting the the t(8;14) in interphase cells. Dual color FISH detection of the t(8;14) in interphase cells is possible by using cosmid clones spanning the c-MYC locus at 8q24 and a differently labelled IgH probe

Additional anomalies Recurrent chromosome aberrations associated with the 8q24 translocations include 1q21‹25 duplications, deletions of 6q11-14, 17p deletions and trisomy 12, +7, +8 and +18.

Genes involved and Proteins

Note
The t(8,14) and the variant t(8;22) and t(2;8) juxtapose IgH sequences and the c-MYC oncogene, bringing about its constitutional expression.
The 17p deletion may have a correlation with p53 loss of function, determined by deletion of one allele and inactivating mutation of the remaining allele

Result of the chromosomal anomaly

Fusion Protein
Oncogenesis Constitutive expression of c-MYC is crucial for the pathogenesis of BL, this protein being a key transcriptional regulator, controlling cell proliferation, differentiation and death. The deregulated expression of c-MYC, caused by the 8q24 translocations, is achieved through multiple mechanisms: a) juxtaposition to regulatory elements of the Ig loci, b) mutations in the c-MYC 5' regulatory regions and, c) aminoacid substitutions occurring in exon 2, making the c-MYC transactivation domain less susceptible to modulation

Bibliography

Chromosomal abnormalities in adult non-endemic Burkitt's lymphoma and leukemia: 22 new reports and a review of 148 cases from the literature.

Kornblau SM, Goodacre A, Cabanillas F

Hematological oncology. 1991 ; 9 (2) : 63-78.

PMID 1869243

A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group.

Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC

Blood. 1994 ; 84 (5) : 1361-1392.

PMID 8068936

Catalogue of chromosome aberrations in cancer (5th edition).

Mitelmam F ed

Wiley Liss, New York. 1994.

High frequency of EBV association with non-random abnormalities of the chromosome region 1q21-25 in AIDS-related Burkitt's lymphoma-derived cell lines.

Polito P, Cilia AM, Gloghini A, Cozzi M, Perin T, De Paoli P, Gaidano G, Carbone A

International journal of cancer. Journal international du cancer. 1995 ; 61 (3) : 370-374.

PMID 7729949

Molecular genetics of malignant lymphoma. In: Fo?¬Ý R (ed): Reviews in clinical and experimental hematology.

Gaidano G

Forum Service Editore, Genova and Martin Dunitz, London,. 1997.

Small noncleaved cell lymphomas (Burkitt's and Burkitt-like lymphomas).

Magrath I

In. : page M.

Application of interphase fluorescence in situ Hybridization for the detection of the Burkitt translocation t(8;14)(q24;q32) in B-cell lymphomas.

Siebert R, Matthiesen P, Harder S, Zhang Y, Borowski A, Zˆºhlke-Jenisch R, Metzke S, Joos S, Weber-Matthiesen K, Grote W, Schlegelberger B

Blood. 1998 ; 91 (3) : 984-990.

PMID 9446660

World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997.

Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1999 ; 17 (12) : 3835-3849.

PMID 10577857

Small noncleaved, non-Burkitt's (Burkit-Like) lymphoma: cytogenetics predict outcome and reflect clinical presentation.

Macpherson N, Lesack D, Klasa R, Horsman D, Connors JM, Barnett M, Gascoyne RD

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1999 ; 17 (5) : 1558-1567.

PMID 10334544

Clinicopathogenetic significance of chromosomal abnormalities in patients with blastic peripheral B-cell lymphoma. Kiel-Wien-Lymphoma Study Group.

Schlegelberger B, Zwingers T, Harder L, Nowotny H, Siebert R, Vesely M, Bartels H, Sonnen R, Hopfinger G, Nader A, Ott G, Mˆºller-Hermelink K, Feller A, Heinz R

Blood. 1999 ; 94 (9) : 3114-3120.

PMID 10556197

Contributor(s)

Written 03-2001 Antonio Cuneo and Gianluigi Castoldi

Citation

This paper should be referenced as such :
Cuneo A, Castoldi GL . Burkitt's lymphoma (BL). Atlas Genet Cytogenet Oncol Haematol. March 2001 .
URL : http://AtlasGeneticsOncology.org/Genes/BurkittID2077.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Dec 6 18:01:21 2008

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jlhuret@AtlasGeneticsOncology.org.

Phenotype / cell stem origin	Pan-B antigens positive; TdT-, CD10+; CD5-; sIgM+. The cell of origin is a peripheral IgM+ memory B-cell (presence of somatic hypermutation of the Ig gene)
Epidemiology	Most common in children (1/3 of lymphomas). In adult it accounts for 3-4% of all lymphomas in western countries and it is frequently associated with immunodeficiency
Clinics	There is an endemic variant, affecting africans, which primarily involves the jaws and other facial bones. The non-endemic variant may be associated with immunodeficiency states and usually presents with abdominal involvement (distal ileum, ciecum, mesentery). The disease is very aggressive and requires prompt treatment with appropriate regimens.
Cytology	The blast cells in the peripheral blood and bone marrow display a basophilic cytoplasm with characteristic vacuolization, a picture indisinguishable from acute lymphoblastic leukemia (ALL) L3 of the FAB classification, which represents the leukemic counterpart of BL.
Pathology	The lymphoma consists of a monomorphic infiltrate of the lymph node by medium-sized cells showing round nuclei with several nucleoli and basophilic cytoplasm. Numerous benign macrophages confer a histologic pattern referred to as ³starry sky². Involvement of the peripheral blood and bone marrow may occur. The related form ³Burkitt-like² lymphoma shows intermediate features between diffuse large cell lymphoma and BL and probably includes different disease entities. It was suggested by the WHO panel that only those cases with c-MYC rearrangement and/or a >99% proliferation fraction as demonstrated by Ki-67 positivity should be classified as Burkitt-like lymphoma
Treatment	Aggressive regimens specifically designed for this lymphoma must be used
Evolution	Very rapid if untreated. Patients with limited disease and favourable prognostic features at presentation may rapidly show disease dissemination
Prognosis	If treated promptly with appropriate regimens the majority of patients can be cured

Cytogenetics Morphological	The primary chromosome anomaly is the translocation t(8;14)(q24;q32), found in 60-70% of the cases. Variant translocations having in common an 8q24 break, i.e the t(8;22)(q24;q11) and t(2;8)(p12;q24) occur in approximately 10-15% and 2-5% of the cases, respectively. A minority of cases may carry a duplication of chromosome 1, involving the 1q21-25 segment as the only detectable chromosome lesion In the Burkitt-like form there are at least 3 cytogenetic categories: one with an 8q24/c-MYC translocation, one with an 8q24 and 18q21/ BCL2 translocation and another with ³miscellaneous² rearrangements, frequently including an 18q21 break
Probes	Conventional karyotyping is the method of choice for the detection of the 8q24 translocations occurring in BL. There is variability in the location of the breakpoint at band 8q24, making the detection of c-MYC rearrangement (see below) difficult by molecular genetics. Southern blotting is the preferred method. In the endemic form the breakpoint in the Ig locus is usually located in the Ig heavy chain variable region, whereas in the nonendemic form the breakpoint falls in the Ig switch region. Fluorescence in situ hybridization is of value in detecting the the t(8;14) in interphase cells. Dual color FISH detection of the t(8;14) in interphase cells is possible by using cosmid clones spanning the c-MYC locus at 8q24 and a differently labelled IgH probe
Additional anomalies	Recurrent chromosome aberrations associated with the 8q24 translocations include 1q21‹25 duplications, deletions of 6q11-14, 17p deletions and trisomy 12, +7, +8 and +18.