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Mantle cell lymphoma (incomplete)

Clinics and Pathology

Disease NHL of the low to intermediate grade
Phenotype / cell stem origin B-cell lineage
Epidemiology 5% of NHL; sex ratio: 3M/1F; median age: 65 yrs
Clinics advanced disease (Ann Harbor stage III-IV) with generalized lymphadenopathies in 90%, bone marrow involvement (70%), frequent splenomegaly (50%), hepatomegaly (30%), and gastro-intestinal involvement (20%), and lymphocytosis (30%); elevated LDH in 50%
 
Leukemic phase of mantle cell lymphoma. Peripheral blood. Small to medium sized lymphoid cells with slightly to markedly irregular nuclear contour. The nuclei have moderately dispersed chromatin bur inconspicuous nucleoli. From a patient with 46,XX,t(11;14)(q13;q32) - Courtesy Georges Flandrin.
Pathology small cleaved cell B-lymphocytes with inconspicuous nucleoli and pale cytoplasm; with a pan B-cell, CD5+, CD10-, CD23- (in contrast with CLL) phenotype; diffuse, nodular and blastoid types, the latter having large cells and higher mitotic count
Treatment according to the age and the disease stage
Prognosis median survival is 3 to 4 yrs; less than 2 yrs in the case of a leukaemic form (blastoid); in contrast with the good prognosis of the MALT lymphoma, a closely related disease.

Cytogenetics

Cytogenetics Morphological
  • knowledge is still scarce, and data complex
  • t(11;14)(q13;q32) is found in 50-70% of cases, but this translocation may also, at a much lesser frequency, be found in other diseases; the genes involved in this translocation are described below; t(11;14) is found in complex karyotypes
  • other frequent findings: deletion of parts of :1p, 6q 9p, 11q (in particular 11q22-23), 13q; gains of parts of: 3q, 8q, 15q; frequent markers; tetraploidy may be found, especially in the blastoid subtype
  • Cytogenetics Molecular CGH (compatrative genomic hybridization) may disclose important events in this disease, taken into account that the t(11;14) may be insufficient for oncogenesis; furthermore, this and other molecular cytogenetic techniques may come in addition to the usual techniques to "dissect" complex karyotypes

    Genes involved and Proteins

    Gene Name BCL1
    Location 11q13
    Dna / Rna 5 exons
    Protein encodes the cyclin D1; role in the cell cycle control: G1 progression and G1/S transition
    Gene Name IgH
    Location 14q32

    Result of the chromosomal anomaly

    Hybrid gene
    Description 5' BCL1 translocated on chromosome 14 near JH (junctions genes of IgH) and C in 3'; the breakpoint in BCL1 is in MTC (major translocation cluster), centromeric to the gene (in 5'), in 80% of cases, or dispersed in mTC1, 2, or 3 in 5'of the gene or in the 3' untranslated region of exon 5.
      
    Fusion Protein
    Description no fusion protein, but promoter exchange; the immunoglobulin gene enhancer stimulates the expression of BCL1.
    Oncogenesis overexpression of BCL1 accelerates passage through the G1 phase
      

    Bibliography

    Rearrangement and overexpression of the BCL-1/PRAD-1 gene in intermediate lymphocytic lymphomas and in t(11q13)-bearing leukemias.
    Rimokh R, Berger F, Delsol G, Charrin C, Berthˆ©as MF, Ffrench M, Garoscio M, Felman P, Coiffier B, Bryon PA
    Blood. 1993 ; 81 (11) : 3063-3067.
    PMID 8499640
     
    Non-Hodgkin's lymphoma.
    Maloney DG
    Current opinion in hematology. 1995 ; 2 (4) : 255-261.
    PMID 9372005
     
    Cytogenetics of lymphomas: a brief review of its theoretical and practical significance.
    Donner LR
    Cancer genetics and cytogenetics. 1997 ; 94 (1) : 20-26.
    PMID 9078287
     
    Mantle cell lymphoma: a clinicopathologic study of 80 cases.
    Argatoff LH, Connors JM, Klasa RJ, Horsman DE, Gascoyne RD
    Blood. 1997 ; 89 (6) : 2067-2078.
    PMID 9058729
     
    Mantle cell lymphoma: diagnostic criteria, clinical aspects and therapeutic problems.
    Meusers P, Hense J, Brittinger G
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1997 ; 11 Suppl 2 : S60-S64.
    PMID 9178843
     
    Mantle cell lymphoma: presenting features, response to therapy, and prognostic factors.
    Bosch F, Lˆ„pez-Guillermo A, Campo E, Ribera JM, Conde E, Piris MA, Vallespˆ‚ T, Woessner S, Montserrat E
    Cancer. 1998 ; 82 (3) : 567-575.
    PMID 9452276
     
    Blastoid variants of mantle cell lymphoma: frequent bcl-1 rearrangements at the major translocation cluster region and tetraploid chromosome clones.
    Ott G, Kalla J, Ott MM, Schryen B, Katzenberger T, Mˆºller JG, Mˆºller-Hermelink HK
    Blood. 1997 ; 89 (4) : 1421-1429.
    PMID 9028966
     
    Gain of 3q and deletion of 11q22 are frequent aberrations in mantle cell lymphoma.
    Monni O, Oinonen R, Elonen E, Franssila K, Teerenhovi L, Joensuu H, Knuutila S
    Genes, chromosomes & cancer. 1998 ; 21 (4) : 298-307.
    PMID 9559341
     

    Contributor(s)

    Written05-1998Jean-Loup Huret

    Citation

    This paper should be referenced as such :
    Huret JL . Mantle cell lymphoma (incomplete). Atlas Genet Cytogenet Oncol Haematol. May 1998 .
    URL : http://AtlasGeneticsOncology.org/Anomalies/mantle2062.html

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Mon May 12 18:11:46 2008


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