Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Burkitt's lymphoma (BL)

Written2001-03Antonio Cuneo, Gianluigi Castoldi
Hematology Section, Department of Biomedical Sciences, University of Ferrara, Corso Giovecca 203, Ferrara, Italy
Updated2018-01Luis Miguel Juárez Salcedo, Ana Corazón Monzón, Samir Dalia
Principe de Asturias University Hospital, Madrid, Spain (LMJS); Clinic Valladolid University Hospital, Valladolid, Spain (ACM); Oncology and Hematology, Mercy Clinic Joplin, Joplin, MO, USA (SD).

Abstract Review on Burkitt's lymphoma, with data on clinics, and the genes involved.

Keywords Burkitt's lymphoma; MYC; IGH; IGK; IGL

(Note : for Links provided by Atlas : click)


ICD-Morpho 9687/3 Burkitt lymphoma
Atlas_Id 2077
Other namesBurkitt's tumor
Malignant lymphoma Burkitt's type

Clinics and Pathology

Phenotype / cell stem origin Pan-B antigens positive (CD19, CD20, CD21, CD22 and CD79a); co-expression of CD10 and Bcl-6. TdT-, CD5-, CD23-, Bcl-2- and CD138-; sIgM+. The cell of origin is a peripheral IgM+ memory B-cell (presence of somatic hypermutation of the Ig gene). Ki67 expression is close to 100% of neoplastic cells.
Etiology Burkitt lymphoma (BL) originates from germinal or post-germinal center B cells. The three clinical subtypes are: endemic, sporadic and immunodeficiency-related. All of these likely arise from B cells at different stages of development.
The development of BL is dependent upon the constitutive expression of the MYC proto-oncogene located at chromosome 8q24. The transcription of MYC protein modulates the expression of target genes that regulate many cell processes including cell growth, division, metabolism and apoptosis.
Chronic Epstein-Barr virus (EVB) infection appears to play a role in all cases of endemic BL and minority of sporadic and immunodeficiency-associated BL (Klapproth and Wirth, 2010).
Epidemiology Most common in children (1/3 of lymphomas). Endemic BL is mainly confined to equatorial Africa where it accounts for 30-50% of all childhood cancers diagnosed each year (3-6 cases per 100.000 children).
Sporadic variant is mostly seen in the US and Western Europe. 30% of pediatric lymphomas and <1% of adult NHL.
3 distinct peaks at around age 10, 40 and in the elderly. In all groups, most patients are male with a 3:1 or 4:1 male to female ratio (Magrath, 2012).
  • African endemic variant usually develops in children with a jaw or facial bone tumor; initial involvement of the abdomen is less common.
    The primary tumor can spread to mesentery, ovary, testis, kidney, breast, and meninges, spreading to lymph nodes, mediastinum, and spleen less frequently.
  • The non-endemic variant may be associated with immunodeficiency states and usually presents with abdominal involvement (distal ileum, ciecum, mesentery). Presenting symptoms can be related to bowel obstruction or gastrointestinal bleeding, mimicking acute appendicitis or intussusception. Lymphadenopathy is generally localized.
    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.
    WHO recognize three different types of Burkitt Lymphoma:
  • Classic Burkitt lymphoma: Characterized for the monomorphic medium-size blast proliferation, with lax chromatin, multiple nucleolis and intense basophilic cytoplasm.
  • Plasmablastic Burkitt Lymphoma and Atypical Burkitt lymphoma: Cells with nuclear pleomorphism and nucleoli of big size but in inferior number to the observed in the classic form.
    The three variants, blastic cells can be associated with plenty mitotic images.
  • Pathology The tumor mass demonstrate complete effacement of the normal architecture by sheets of atypical lymphoid cells.
  • At low power, the tumor has a 'mouth-eaten' appearance, often with interspersed areas of coagulative necrosis or hemorrhage. High rate of proliferation and high rate of apoptotic cell death is observed. A classic 'starry-sky' pattern is usually present, imparted by numerous benign macrophages that have ingested apoptotic tumor cells. The benign histiocytes are large with abundant, clear cytoplasm and are dispersed throughout of basophilic tumor cells.
  • At high power, classically are monomorphic, medium-size cells with round nuclei, multiple dark nucleoli, and basophilic cytoplasm.
    The related form 'Burkitt-like' 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 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.
    Multiple intensive regimens demonstrate excellent activity in BL and are composed of doxorubicin, alkylators, vincristine, and etoposide combined with therapy directed at the eradication and/or prevention of central nervous system disease.
    In patients younger than 60 years of age, including those with well-controlled HIV, and those up to 70 years of age with good baseline functional status, CODOX-M is recommended.
    Patients with extensive disease and elevated LDH, 2 cycles each of R-CODOX-M and R-IVAC can be used.
    For patients with low-risk disease (a single site of disease and normal LDH) 3 cycles of R-CODOX-M.
    For patients with preexisting organ dysfunction, or significant comorbidities and patients older than 60 years of age with low-risk disease, DA-REPOCH could be considering a great option associated with IT therapy or systemic methotrexate upon the completion of cycle 6.
    The addition of rituximab to hyper-CVAD may improve outcome in adult BL or B-ALL, particularly in elderly patients (Castillo et al., 2013; Jacobson and LaCasce, 2014; Dozzo et al., 2016).
    Evolution Apart from the occasional refractory case, a few responsive BL patients will relapse soon after treatment completion and generally within the first 6 months of follow-up.
    Results in refractory/relapsed BL are extremely poor, and new options are urgently needed.
    Relapse and progression frequency varies according to first-line treatment used.
    In chemoresistant disease cases, experimental therapies, due to the globally poor results of traditional salvage programs, should be considered in all refractory or relapsed cases.
    Prognosis If treated promptly with appropriate regimens the majority of patients can be cured.


    Cytogenetics Morphological The molecular hallmark of BL is the translocation of the MYC proto-oncogene to the Ig heavy or 1 light chain genes, leading to constitutive MYC activation. In classic BL, either endemic type or sporadic type, 90-95% of Ig loci are involved, 85% for t(8:14)/ IgH-MYC, 10% for t(8;22)(q24;q11) /Ig-lambda /MYC and approximately 5% for t(2;8)(p12;q24) /Ig-kappa/MYC.
  • In the Burkitt-like form there are at least 3 cytogenetic categories: one with an 8q24/MYC translocation, one with an 8q24 and 18q21/ BCL2 translocation and another with "miscellaneous" rearrangements, frequently including an 18q21 break (Bellan et al., 2005).
  • 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

    Gene NameMYC
    Location 8q24.21
    Protein MYC functions as a transcriptional regulator. MYC binds to MAX that is an obligate heterodimeric partner for MYC in mediating its functions. The MYC-MAX complex is a potent activator of transcription. Thousands of MYC target genes have been identified. Genes targeted by MYC include mediators of metabolism, biosynthesis, and cell cycle progression (Mohamed 2017).
    Gene NameIGH
    Location 14q32.33
    Note Alternatively: IGK, located in 2p11.2 or IGL, located in 22q11.22

    Result of the chromosomal anomaly

    Fusion Protein
    Oncogenesis Constitutive expression of 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 MYC, caused by the 8q24 translocations, is achieved through multiple mechanisms: a) juxtaposition to regulatory elements of the Ig loci, b) mutations in the MYC 5' regulatory regions and, c) aminoacid substitutions occurring in exon 2, making the MYC transactivation domain less susceptible to modulation (Hecht and Aster, 2000).
    Additional gene alterations include the following: truncating mutations of ARID1A and amplification of MCL1; point mutations of LRP6; truncating alterations of LRP1B, PTPRD, PTEN, NOTCH1, and ATM; amplifications of RAF1, MDM4, MDM2, KRAS, IKBKE, and CDK6; deletion of CDKN2A; overexpression ofMIR17HG; activating mutations of TCF3 and/or inactivating mutations of its negative regulator ID3; and CCND3 activating mutations (Havelange et al., 2016).


    Immunoglobulin gene analysis reveals 2 distinct cells of origin for EBV-positive and EBV-negative Burkitt lymphomas
    Bellan C, Lazzi S, Hummel M, Palummo N, de Santi M, Amato T, Nyagol J, Sabattini E, Lazure T, Pileri SA, Raphael M, Stein H, Tosi P, Leoncini L
    Blood 2005 Aug 1;106(3):1031-6
    PMID 15840698
    Population-based prognostic factors for survival in patients with Burkitt lymphoma: an analysis from the Surveillance, Epidemiology, and End Results database
    Castillo JJ, Winer ES, Olszewski AJ
    Cancer 2013 Oct 15;119(20):3672-9
    PMID 23913575
    Molecular genetics of malignant lymphoma. In: Fo R (ed): Reviews in clinical and experimental hematology.
    Gaidano G
    Forum Service Editore, Genova and Martin Dunitz, London,. 1997. Catalogue of chromosome aberrations in cancer (5th edition). Mitelmam F ed Wiley Liss, New York. 1994.
    The present and future medicolegal importance of record keeping in anesthesia and intensive care: the case for automation
    Gibbs RF
    J Clin Monit 1989 Oct;5(4):251-5
    PMID 2809669
    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
    J Clin Oncol 1999 Dec;17(12):3835-49
    PMID 10577857
    Genetic differences between paediatric and adult Burkitt lymphomas
    Havelange V, Pepermans X, Ameye G, Théate I, Callet-Bauchu E, Barin C, Penther D, Lippert E, Michaux L, Mugneret F, Dastugue N, Raphaül M, Vikkula M, Poirel HA
    Br J Haematol 2016 Apr;173(1):137-44
    PMID 26887776
    Molecular biology of Burkitt's lymphoma
    Hecht JL, Aster JC
    J Clin Oncol 2000 Nov 1;18(21):3707-21
    PMID 11054444
    How I treat Burkitt lymphoma in adults
    Jacobson C, LaCasce A
    Blood 2014 Nov 6;124(19):2913-20
    PMID 25258344
    Advances in the understanding of MYC-induced lymphomagenesis
    Klapproth K, Wirth T
    Br J Haematol 2010 May;149(4):484-97
    PMID 20346013
    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
    Hematol Oncol 1991 Mar-Apr;9(2):63-78
    PMID 1869243
    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
    J Clin Oncol 1999 May;17(5):1558-67
    PMID 10334544
    MYC (MYC proto-oncogene, bHLH transcription factor)
    Mohamed AN
    Atlas Genet Cytogenet Oncol Haematol. in press. On line version :
    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
    Int J Cancer 1995 May 4;61(3):370-4
    PMID 7729949
    Clinicopathogenetic significance of chromosomal abnormalities in patients with blastic peripheral B-cell lymphoma
    Schlegelberger B, Zwingers T, Harder L, Nowotny H, Siebert R, Vesely M, Bartels H, Sonnen R, Hopfinger G, Nader A, Ott G, Müller-Hermelink K, Feller A, Heinz R
    Kiel-Wien-Lymphoma Study Group Blood
    PMID 10556197
    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, Zühlke-Jenisch R, Metzke S, Joos S, Weber-Matthiesen K, Grote W, Schlegelberger B
    Blood 1998 Feb 1;91(3):984-90
    PMID 9446660


    This paper should be referenced as such :
    Juárez Salcedo LM, Corazón Monzón A, Dalia S
    Burkitt's lymphoma (BL);
    Atlas Genet Cytogenet Oncol Haematol. in press
    On line version :
    History of this paper:
    Cuneo, A ; Castoldi, GL. Burkitt's lymphoma (BL). Atlas Genet Cytogenet Oncol Haematol. 2001;5(2):121-122.

    Other genes implicated (Data extracted from papers in the Atlas) [ 26 ]


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