Prognostic usage of VH gene mutation status and its surrogate markers and the role of antigen selection in chronic lymphocytic leukemia

被引:18
作者
Tobin, G [1 ]
Rosenquist, R [1 ]
机构
[1] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, Uppsala, Sweden
关键词
chronic lymphocytic leukemia; prognosis; immunoglobulin genes; V-H gene mutation status; CD38; ZAP-70; antigen selection; V(H)3-21 usage;
D O I
10.1385/MO:22:3:217
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
B-cell chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease with many patients surviving for decades with minimal or no treatment, whereas others succumb rapidly to their disease despite therapy. In recent years, new molecular prognostic factors have emerged in CLL that have significantly improved the subgrouping of the disease. One of the most important molecular predictors, the immunoglobulin V-H gene mutation status, divides CLL into two prognostic groups, depending on the presence or absence of somatic hypermutation, where unmutated VH genes are associated with considerably worse prognosis than mutated V-H genes. An exception to this appears to be CLL patients utilizing the V(H)3-21 gene as they have poor outcome irrespective of mutation status. Surrogate markers for the V-H gene mutation status have been suggested, such as CD38 and ZAP-70 expression. However, the CD38 level was later shown to display poor correlation to the mutation status, although it may still serve as an independent prognostic factor. More promising is the expression levels of ZAP-70, which appears to be both a strong surrogate marker for V-H gene mutation status, although discrepancies have been reported, as well as an independent prognostic marker. Immunoglobulin gene analysis has also indicated the possibility of antigen selection in CLL considering the significant bias in V-H gene usage. Intriguingly, the V(H)3-21(+) group and several other CLL subsets using certain V-H genes was recently reported to display strikingly restricted immunoglobulin gene features, in both their heavy and light chain gene rearrangements, thus further high-lighting the possible role of antigen involvement in CLL development.
引用
收藏
页码:217 / 228
页数:12
相关论文
共 94 条
  • [1] Immunohistochemical detection of ZAP-70 in 341 cases of non-Hodgkin and Hodgkin lymphoma
    Admirand, JH
    Rassidakis, GZ
    Abruzzo, LV
    Valbuena, JR
    Jones, D
    Medeiros, LJ
    [J]. MODERN PATHOLOGY, 2004, 17 (08) : 954 - 961
  • [2] JOINING OF IMMUNOGLOBULIN HEAVY-CHAIN GENE SEGMENTS - IMPLICATIONS FROM A CHROMOSOME WITH EVIDENCE OF 3 D-JH FUSIONS
    ALT, FW
    BALTIMORE, D
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1982, 79 (13): : 4118 - 4122
  • [3] Identification of a potential role for POU2AFI and BTG4 in the deletion of 11q23 in chronic lymphocytic leukemia
    Auer, RL
    Starczynski, J
    McElwaine, S
    Bertoni, F
    Newland, AC
    Fegan, CD
    Cotter, FE
    [J]. GENES CHROMOSOMES & CANCER, 2005, 43 (01) : 1 - 10
  • [4] The mechanism and regulation of chromosomal V(D)J recombination
    Bassing, CH
    Swat, W
    Alt, FW
    [J]. CELL, 2002, 109 : S45 - S55
  • [5] BINET JL, 1981, CANCER-AM CANCER SOC, V48, P198, DOI 10.1002/1097-0142(19810701)48:1<198::AID-CNCR2820480131>3.0.CO
  • [6] 2-V
  • [7] Bullrich F, 1999, CANCER RES, V59, P24
  • [8] Conversion of CD38 and/or myeloid-associated marker expression status during the course of B-CLL: association with a change to an aggressive clinical course
    Chang, CC
    Cleveland, RP
    [J]. BLOOD, 2002, 100 (03) : 1106 - 1106
  • [9] Chen SH, 2002, STUD FUZZ SOFT COMP, V100, P3
  • [10] CD38 expression and secondary 17p deletion are important prognostic factors in chronic lymphocytic leukaemia
    Chevallier, P
    Penther, D
    Avet-Loiseau, H
    Robillard, N
    Ifrah, N
    Mahé, B
    Hamidou, M
    Maisonneuve, H
    Moreau, P
    Jardel, H
    Harousseau, JL
    Bataille, R
    Garand, R
    [J]. BRITISH JOURNAL OF HAEMATOLOGY, 2002, 116 (01) : 142 - 150