Update on the biology of chronic lymphocytic leukemia.

An understanding of the molecular biology of B-cell chronic lymphocytic leukemia (B-CLL) has led to the appreciation that several different B-cell diseases are represented under this name. Variability in the bcl-2 family of proteins, p53 mutation, or the presence of various chromosomal abnormalities corresponds to variability of the clinical course of disease and response to therapy. Differential expression of cell surface adhesion molecules by B-CLL cells have also been shown to influence clinical outcome, as have the expression of immune regulatory molecules (eg, CD80, CD40R, CD27 and CD79b). Recent work studying immunoglobulin-heavy chain gene rearrangement postulates at least two subsets of B-CLL originating from different stages of B-cell development and following different clinical courses. The knowledge that B-CLL is the final consequence of many different molecular perturbations may allow the development of chemotherapies, immunotherapies, and gene therapies that target the specific molecular defect in a given case of B-CLL.

[1]  N. Chiorazzi,et al.  Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. , 1999, Blood.

[2]  J. D. Capra,et al.  Mutational Status of Ig VH Genes Provides Clinically Valuable Information in B-Cell Chronic Lymphocytic Leukemia , 1999 .

[3]  T J Hamblin,et al.  Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. , 1999, Blood.

[4]  P. Circosta,et al.  An alternatively spliced form of CD79b gene may account for altered B-cell receptor expression in B-chronic lymphocytic leukemia. , 1999, Blood.

[5]  R. Buhmann,et al.  CD40-activated B-cell chronic lymphocytic leukemia cells for tumor immunotherapy: stimulation of allogeneic versus autologous T cells generates different types of effector cells. , 1999, Blood.

[6]  G. Salles,et al.  Translocations involving the short arm of chromosome 17 in chronic B-lymphoid disorders: frequent occurrence of dicentric rearrangements and possible association with adverse outcome , 1999, Leukemia.

[7]  A. García-Pardo,et al.  Fibronectin interaction with α4β1 integrin prevents apoptosis in B cell chronic lymphocytic leukemia: correlation with Bcl-2 and Bax , 1999, Leukemia.

[8]  H. Döhner,et al.  Reduced expression of adhesion molecules and cell signaling receptors by chronic lymphocytic leukemia cells with 11q deletion. , 1999, Blood.

[9]  T. Tötterman,et al.  Elevated serum levels of soluble vascular cell adhesion molecule‐1 (sVCAM‐1) closely reflect tumour burden in chronic B‐lymphocytic leukaemia , 1998, British journal of haematology.

[10]  M. Grever,et al.  Flavopiridol induces apoptosis in chronic lymphocytic leukemia cells via activation of caspase-3 without evidence of bcl-2 modulation or dependence on functional p53. , 1998, Blood.

[11]  D. Lane,et al.  The p53 tumour suppressor gene , 1998, The British journal of surgery.

[12]  R. Greil,et al.  Differential sensitivity of CD4+ and CD8+ T lymphocytes to the killing efficacy of Fas (Apo-1/CD95) ligand+ tumor cells in B chronic lymphocytic leukemia. , 1998, Blood.

[13]  C. Croce,et al.  Expression of apoptosis-regulating proteins in chronic lymphocytic leukemia: correlations with In vitro and In vivo chemoresponses. , 1998, Blood.

[14]  A. Challa,et al.  Release of clonal block in B cell chronic lymphocytic leukaemia by engagement of co-operative epitopes on CD40. , 1998, Leukemia research.

[15]  K. Tanaka,et al.  Identification of a commonly deleted region at 17p13.3 in leukemia and lymphoma associated with 17p abnormality , 1998, Leukemia.

[16]  G. Juliusson,et al.  Cytogenetics in chronic lymphocytic leukemia. , 1998, Seminars in oncology.

[17]  M. Grever,et al.  Old and new therapies in chronic lymphocytic leukemia: now is the time for a reassessment of therapeutic goals. , 1998, Seminars in oncology.

[18]  J. Gabrilove,et al.  The novel cyclin-dependent kinase inhibitor flavopiridol downregulates Bcl-2 and induces growth arrest and apoptosis in chronic B-cell leukemia lines. , 1997, Blood.

[19]  J. Gribben,et al.  In Vivo Expression of B7-1 and B7-2 By Follicular Lymphoma Cells Can Prevent Induction of T-Cell Anergy But Is Insufficient to Induce Significant T-Cell Proliferation , 1997 .

[20]  D. P. Bentley,et al.  Bcl-2/Bax ratios in chronic lymphocytic leukaemia and their correlation with in vitro apoptosis and clinical resistance. , 1997, British Journal of Cancer.

[21]  T. Kipps,et al.  Acquired CD40-ligand deficiency in chronic lymphocytic leukemia , 1997, Nature Medicine.

[22]  F Gambale,et al.  Inhibition of Bax channel-forming activity by Bcl-2. , 1997, Science.

[23]  D. Oscier,et al.  Differential rates of somatic hypermutation in V(H) genes among subsets of chronic lymphocytic leukemia defined by chromosomal abnormalities. , 1997, Blood.

[24]  J. Ceuppens,et al.  CD40 triggering of chronic lymphocytic leukemia B cells results in efficient alloantigen presentation and cytotoxic T lymphocyte induction by up-regulation of CD80 and CD86 costimulatory molecules , 1997, Leukemia.

[25]  M. James,et al.  11q deletions identify a new subset of B-cell chronic lymphocytic leukemia characterized by extensive nodal involvement and inferior prognosis. , 1997, Blood.

[26]  T. Manshouri,et al.  Expression profile of MDM‐2 proteins in chronic lymphocytic leukemia and their clinical relevance , 1997, American journal of hematology.

[27]  C. Pepper,et al.  REGULATION OF CLINICAL CHEMORESISTANCE BY bcl‐2 AND BAX ONCOPROTEINS IN B‐CELL CHRONIC LYMPHOCYTIC LEUKAEMIA , 1996, British journal of haematology.

[28]  M. Caligiuri,et al.  Minimal region of loss at 13q14 in B-cell chronic lymphocytic leukemia. , 1996, Blood.

[29]  Isabel María del Águila Cano,et al.  Trisomy 12 and p53 deletion in chronic lymphocytic leukemia detected by fluorescence in situ hybridization: association with morphology and resistance to conventional chemotherapy. , 1996, Cancer genetics and cytogenetics.

[30]  J. Burthem,et al.  Integrin function in chronic lymphocytic leukemia. , 1996, Blood.

[31]  R. Meadows,et al.  X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death , 1996, Nature.

[32]  John Calvin Reed,et al.  Drug-induced apoptosis in B-cell chronic lymphocytic leukemia: relationship between p53 gene mutation and bcl-2/bax proteins in drug resistance. , 1996, Oncogene.

[33]  D. Catovsky,et al.  Trisomy 12 defines a group of CLL with atypical morphology: correlation between cytogenetic, clinical and laboratory features in 544 patients , 1996, British journal of haematology.

[34]  D. Oscier,et al.  Trisomy 12 and structural abnormalities of 13q14 occurring in the same clone in chronic lymphocytic leukaemia , 1996, British journal of haematology.

[35]  L. Foroni,et al.  Human bone marrow stromal cells prevent apoptosis and support the survival of chronic lymphocytic leukaemia cells in vitro , 1996, British journal of haematology.

[36]  T. Kipps,et al.  Expression of CD27 and its ligand, CD70, on chronic lymphocytic leukemia B cells. , 1995, Blood.

[37]  A Benner,et al.  p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell leukemias. , 1995, Blood.

[38]  M. Yellin,et al.  T lymphocyte T cell-B cell-activating molecule/CD40-L molecules induce normal B cells or chronic lymphocytic leukemia B cells to express CD80 (B7/BB-1) and enhance their costimulatory activity. , 1994, Journal of immunology.

[39]  L. Florensa,et al.  Expression of lymphocyte function-associated antigen (LFA)-1 in B-cell chronic lymphocytic leukemia. , 1994, Leukemia & lymphoma.

[40]  E. Newcomb,et al.  p53 gene mutation in B-cell chronic lymphocytic leukemia is associated with drug resistance and is independent of MDR1/MDR3 gene expression , 1993 .

[41]  John Calvin Reed,et al.  bcl-2 Gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia , 1993 .

[42]  I. Katayama,et al.  Surface phenotype and adhesion activity of B-cell chronic lymphoid leukemias. , 1993, Leukemia & lymphoma.

[43]  L. Hawthorn,et al.  The consistent 13q14 translocation breakpoint seen in chronic B-cell leukaemia (BCLL) involves deletion of the D13S25 locus which lies distal to the retinoblastoma predisposition gene. , 1993, Oncogene.

[44]  F. Mandelli,et al.  Adhesion molecule expression on B-cell chronic lymphocytic leukemia cells: malignant cell phenotypes define distinct disease subsets. , 1993, Blood.

[45]  T. Kipps,et al.  Activated T cells induce expression of B7/BB1 on normal or leukemic B cells through a CD40-dependent signal , 1993, The Journal of experimental medicine.

[46]  R. Schwartz.  Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy , 1992, Cell.

[47]  L. Cro,et al.  Differential expression of very late activation antigen-3 (VLA-3)/VLA-4 in B-cell non-Hodgkin lymphoma and B-cell chronic lymphocytic leukemia. , 1992, Blood.

[48]  C. Preudhomme,et al.  Mutations of the p53 gene in B-cell chronic lymphocytic leukemia: a report on 39 cases with cytogenetic analysis. , 1992, Leukemia.

[49]  B. Vogelstein,et al.  p53 mutations in human cancers. , 1991, Science.

[50]  M. Raffeld,et al.  Oncogene rearrangements in chronic B-cell leukemia. , 1991, Blood.

[51]  P. Linsley,et al.  Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation , 1991, The Journal of experimental medicine.

[52]  T. Kipps,et al.  Preferential linkage of bcl-2 to immunoglobulin light chain gene in chronic lymphocytic leukemia , 1990, The Journal of experimental medicine.

[53]  J. H. Pope,et al.  Spontaneous programmed death (apoptosis) of B‐chronic lymphocytic leukaemia cells following their culture in vitro , 1989, British journal of haematology.

[54]  M. Oken,et al.  Multiple recurrent genomic defects in follicular lymphoma. A possible model for cancer. , 1987, The New England journal of medicine.

[55]  C. Bloomfield,et al.  There are differences in cytogenetic abnormalities among histologic subtypes of the non-Hodgkin's lymphomas , 1985 .

[56]  C. Croce,et al.  ATM mutations in B-cell chronic lymphocytic leukemia. , 1999, Cancer research.

[57]  Peter Lichter,et al.  Chromosome aberrations in B-cell chronic lymphocytic leukemia: reassessment based on molecular cytogenetic analysis , 1999, Journal of Molecular Medicine.

[58]  Terry J. Hamblin,et al.  Unmutated Ig VH Genes Are Associated With a More Aggressive Form of Chronic Lymphocytic Leukemia , 1999 .

[59]  M. Goller,et al.  Inhibition of T cell/B cell interaction by B-CLL cells , 1999, Leukemia.

[60]  A. A. Thompson,et al.  Widespread B29 (CD79b) gene defects and loss of expression in chronic lymphocytic leukemia. , 1999, Leukemia & lymphoma.

[61]  C. Pepper,et al.  Elevated Bcl-2/Bax are a consistent feature of apoptosis resistance in B-cell chronic lymphocytic leukaemia and are correlated with in vivo chemoresistance. , 1998, Leukemia & lymphoma.

[62]  R. Greil,et al.  Differential Sensitivity of CD 4 1 and CD 8 1 T Lymphocytes to the Killing Efficacy of Fas ( Apo-1 / CD 95 ) Ligand 1 Tumor Cells in B Chronic Lymphocytic Leukemia , 1998 .

[63]  F. Schriever,et al.  Differential adhesion pattern of B cell chronic lymphocytic leukemia cells , 1998, Leukemia.

[64]  F. Mancini,et al.  p 53 Expression in B-Cell Chronic Lymphocytic Leukemia : A Marker of Disease Progression and Poor Prognosis , 1998 .

[65]  V. Callea,et al.  Bcl-2 protein expression and p53 gene mutation in chronic lymphocytic leukemia: correlation with in vitro sensitivity to chlorambucil and purine analogs. , 1997, Haematologica.

[66]  K. Lee,et al.  P53, MDM-2, BAX and BCL-2 and drug resistance in chronic lymphocytic leukemia. , 1997, Leukemia & lymphoma.

[67]  B. Quesnel,et al.  p53 mutations are associated with resistance to chemotherapy and short survival in hematologic malignancies. , 1994, Blood.

[68]  L. Cro,et al.  Structure and function of VLA integrins: differential expression in B-cell leukemia/lymphoma. , 1994, Leukemia & lymphoma.

[69]  D. de Jong,et al.  Subcellular localization of the bcl-2 protein in malignant and normal lymphoid cells. , 1994, Cancer research.

[70]  John Calvin Reed,et al.  bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia. , 1993, Blood.

[71]  P. Nowell,et al.  Cytogenetic Findings and Survival in B-cell Chronic Lymphocytic Leukemia. Second IWCCLL Compilation of Data on 662 Patients. , 1991, Leukemia & lymphoma.

[72]  C. Bloomfield,et al.  There are differences in cytogenetic abnormalities among histologic subtypes of the non-Hodgkin's lymphomas. , 1985, Blood.

[73]  Á.,et al.  Expression of CD 27 and its Ligand , CD 70 , on Chronic Lymphocytic Leukemia B Cells , 2022 .