Background The mutational status of immunoglobulin heavy-chainvariable-region (IgVH) genes in the leukemic cells of chroniclymphocytic leukemia (CLL) is an important prognostic factorin the disease. We investigated whether the expression of ZAP-70by CLL cells correlated with the IgVH mutational status, diseaseprogression, and survival.
Methods The expression of ZAP-70 was analyzed in T-cell andB-cell lines and in peripheral-blood samples from 56 patientswith CLL with the use of flow cytometry, Western blotting, andimmunohistochemistry. The results were correlated with the IgVHmutational status and clinical outcome.
Results ZAP-70 was detected by flow-cytometric analysis in cellsof T-cell lineage and in leukemic cells from 32 of 56 patientswith CLL. In all patients in whom at least 20 percent of theleukemic cells were positive for ZAP-70, IgVH was unmutated,whereas IgVH mutations were found in 21 of 24 patients in whomless than 20 percent of the leukemic cells were positive forZAP-70 (P<0.001). Concordant results were obtained when ZAP-70expression was assessed by immunohistochemistry or Western blotting.The level of ZAP-70 expression did not change over time (median,37 months) in sequential samples from 30 patients with CLL.Patients with Binet stage A CLL who had at least 20 percentZAP-70positive leukemic cells had more rapid progressionand poorer survival than those with less than 20 percent ZAP-70positivecells.
Conclusions Among patients with CLL, expression of ZAP-70, asdetected by flow-cytometric analysis, correlated with IgVH mutationalstatus, disease progression, and survival.
Source Information
From the Department of Hematology (M.C., F.B., A.L.-G., E.M.) and the Hematopathology Unit (N.V., B.B., D.C., M.R., S.M., E.C.), Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Barcelona, Spain. Ms. Crespo and Drs. Bosch and Villamor contributed equally to the article.
Address reprint requests to Dr. Bosch at the Department of Hematology, Hospital Clínic, Villarroel 170, Barcelona 08036, Spain, or at fbosch{at}clinic.ub.es.
McElligott, A. M., Maginn, E. N., Greene, L. M., McGuckin, S., Hayat, A., Browne, P. V., Butini, S., Campiani, G., Catherwood, M. A., Vandenberghe, E., Williams, D. C., Zisterer, D. M., Lawler, M.
(2009). The Novel Tubulin-Targeting Agent Pyrrolo-1,5-Benzoxazepine-15 Induces Apoptosis in Poor Prognostic Subgroups of Chronic Lymphocytic Leukemia. Cancer Res.
69: 8366-8375
[Abstract][Full Text]
Visone, R., Rassenti, L. Z., Veronese, A., Taccioli, C., Costinean, S., Aguda, B. D., Volinia, S., Ferracin, M., Palatini, J., Balatti, V., Alder, H., Negrini, M., Kipps, T. J., Croce, C. M.
(2009). Karyotype-specific microRNA signature in chronic lymphocytic leukemia. Blood
114: 3872-3879
[Abstract][Full Text]
Delgado, J., Milligan, D. W., Dreger, P.
(2009). Allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: ready for prime time?. Blood
114: 2581-2588
[Abstract][Full Text]
Bosch, F., Abrisqueta, P., Villamor, N., Terol, M. J., Gonzalez-Barca, E., Ferra, C., Gonzalez Diaz, M., Abella, E., Delgado, J., Carbonell, F., Garcia Marco, J. A., Escoda, L., Ferrer, S., Monzo, E., Gonzalez, Y., Estany, C., Jarque, I., Salamero, O., Muntanola, A., Montserrat, E.
(2009). Rituximab, Fludarabine, Cyclophosphamide, and Mitoxantrone: A New, Highly Active Chemoimmunotherapy Regimen for Chronic Lymphocytic Leukemia. JCO
27: 4578-4584
[Abstract][Full Text]
Alonso, R., Lopez-Guerra, M., Upshaw, R., Bantia, S., Smal, C., Bontemps, F., Manz, C., Mehrling, T., Villamor, N., Campo, E., Montserrat, E., Colomer, D.
(2009). Forodesine has high antitumor activity in chronic lymphocytic leukemia and activates p53-independent mitochondrial apoptosis by induction of p73 and BIM. Blood
114: 1563-1575
[Abstract][Full Text]
Johnson, G. G., Sherrington, P. D., Carter, A., Lin, K., Liloglou, T., Field, J. K., Pettitt, A. R.
(2009). A Novel Type of p53 Pathway Dysfunction in Chronic Lymphocytic Leukemia Resulting from Two Interacting Single Nucleotide Polymorphisms within the p21 Gene. Cancer Res.
69: 5210-5217
[Abstract][Full Text]
Stamatopoulos, B., Haibe-Kains, B., Equeter, C., Meuleman, N., Soree, A., De Bruyn, C., Hanosset, D., Bron, D., Martiat, P., Lagneaux, L.
(2009). Gene expression profiling reveals differences in microenvironment interaction between patients with chronic lymphocytic leukemia expressing high versus low ZAP70 mRNA. haematol
94: 790-799
[Abstract][Full Text]
Yin, C. C., Lin, K. I-C., Ketterling, R. P., Knudson, R. A., Medeiros, L. J., Barron, L. L., Huh, Y. O., Luthra, R., Keating, M. J., Abruzzo, L. V.
(2009). Chronic Lymphocytic Leukemia With t(2;14)(p16;q32) Involves the BCL11A and IgH Genes and Is Associated With Atypical Morphologic Features and Unmutated IgVH Genes. Am J Clin Pathol
131: 663-670
[Abstract][Full Text]
Shanafelt, T. D., Kay, N. E., Jenkins, G., Call, T. G., Zent, C. S., Jelinek, D. F., Morice, W. G., Boysen, J., Zakko, L., Schwager, S., Slager, S. L., Hanson, C. A.
(2009). B-cell count and survival: differentiating chronic lymphocytic leukemia from monoclonal B-cell lymphocytosis based on clinical outcome. Blood
113: 4188-4196
[Abstract][Full Text]
Lopez-Guerra, M., Roue, G., Perez-Galan, P., Alonso, R., Villamor, N., Montserrat, E., Campo, E., Colomer, D.
(2009). p65 Activity and ZAP-70 Status Predict the Sensitivity of Chronic Lymphocytic Leukemia Cells to the Selective I{kappa}B Kinase Inhibitor BMS-345541. Clin. Cancer Res.
15: 2767-2776
[Abstract][Full Text]
Hernandez, J. A., Rodriguez, A. E., Gonzalez, M., Benito, R., Fontanillo, C., Sandoval, V., Romero, M., Martin-Nunez, G., de Coca, A. G., Fisac, R., Galende, J., Recio, I., Ortuno, F., Garcia, J. L., de las Rivas, J., Gutierrez, N. C., San Miguel, J. F., Hernandez, J. M.
(2009). A high number of losses in 13q14 chromosome band is associated with a worse outcome and biological differences in patients with B-cell chronic lymphoid leukemia. haematol
94: 364-371
[Abstract][Full Text]
Hewamana, S., Lin, T. T., Rowntree, C., Karunanithi, K., Pratt, G., Hills, R., Fegan, C., Brennan, P., Pepper, C.
(2009). Rel A Is an Independent Biomarker of Clinical Outcome in Chronic Lymphocytic Leukemia. JCO
27: 763-769
[Abstract][Full Text]
BOELENS, J., LUST, S., VANHOECKE, B., OFFNER, F.
(2009). Chronic Lymphocytic Leukaemia. Anticancer Res
29: 605-615
[Abstract][Full Text]
Lewintre, E. J., Martin, C. R., Ballesteros, C. G., Montaner, D., Rivera, R. F., Mayans, J. R., Garcia-Conde, J.
(2009). Cryptochrome-1 expression: a new prognostic marker in B-cell chronic lymphocytic leukemia. haematol
94: 280-284
[Abstract][Full Text]
Rosati, E., Sabatini, R., Rampino, G., Tabilio, A., Di Ianni, M., Fettucciari, K., Bartoli, A., Coaccioli, S., Screpanti, I., Marconi, P.
(2009). Constitutively activated Notch signaling is involved in survival and apoptosis resistance of B-CLL cells. Blood
113: 856-865
[Abstract][Full Text]
Sargent, R., Jones, D., Abruzzo, L. V., Yao, H., Bonderover, J., Cisneros, M., Wierda, W. G., Keating, M. J., Luthra, R.
(2009). Customized Oligonucleotide Array-Based Comparative Genomic Hybridization as a Clinical Assay for Genomic Profiling of Chronic Lymphocytic Leukemia. J. Mol. Diagn.
11: 25-34
[Abstract][Full Text]
Kipps, T. J.
(2009). Chronic Lymphocytic Leukemia: Advances in Assessing Prognosis and Therapy. Am Soc Clin Oncol Ed Book
2009: 385-393
[Abstract][Full Text]
Lopez-Guerra, M., Trigueros-Motos, L., Molina-Arcas, M., Villamor, N., Casado, F. J., Montserrat, E., Campo, E., Colomer, D., Pastor-Anglada, M.
(2008). Identification of TIGAR in the equilibrative nucleoside transporter 2-mediated response to fludarabine in chronic lymphocytic leukemia cells. haematol
93: 1843-1851
[Abstract][Full Text]
Trentin, L., Frasson, M., Donella-Deana, A., Frezzato, F., Pagano, M. A., Tibaldi, E., Gattazzo, C., Zambello, R., Semenzato, G., Brunati, A. M.
(2008). Geldanamycin-induced Lyn dissociation from aberrant Hsp90-stabilized cytosolic complex is an early event in apoptotic mechanisms in B-chronic lymphocytic leukemia. Blood
112: 4665-4674
[Abstract][Full Text]
Pepper, C., Lin, T. T., Pratt, G., Hewamana, S., Brennan, P., Hiller, L., Hills, R., Ward, R., Starczynski, J., Austen, B., Hooper, L., Stankovic, T., Fegan, C.
(2008). Mcl-1 expression has in vitro and in vivo significance in chronic lymphocytic leukemia and is associated with other poor prognostic markers. Blood
112: 3807-3817
[Abstract][Full Text]
Sorror, M. L., Storer, B. E., Sandmaier, B. M., Maris, M., Shizuru, J., Maziarz, R., Agura, E., Chauncey, T. R., Pulsipher, M. A., McSweeney, P. A., Wade, J. C., Bruno, B., Langston, A., Radich, J., Niederwieser, D., Blume, K. G., Storb, R., Maloney, D. G.
(2008). Five-Year Follow-Up of Patients With Advanced Chronic Lymphocytic Leukemia Treated With Allogeneic Hematopoietic Cell Transplantation After Nonmyeloablative Conditioning. JCO
26: 4912-4920
[Abstract][Full Text]
Shim, J.-H., Choi, H. S., Pugliese, A., Lee, S.-Y., Chae, J.-I., Choi, B. Y., Bode, A. M., Dong, Z.
(2008). (-)-Epigallocatechin Gallate Regulates CD3-mediated T Cell Receptor Signaling in Leukemia through the Inhibition of ZAP-70 Kinase. J. Biol. Chem.
283: 28370-28379
[Abstract][Full Text]
Rossi, D., Zucchetto, A., Rossi, F. M., Capello, D., Cerri, M., Deambrogi, C., Cresta, S., Rasi, S., De Paoli, L., Bodoni, C. L., Bulian, P., Del Poeta, G., Ladetto, M., Gattei, V., Gaidano, G.
(2008). CD49d expression is an independent risk factor of progressive disease in early stage chronic lymphocytic leukemia. haematol
93: 1575-1579
[Abstract][Full Text]
Galletti, J., Canones, C., Morande, P., Borge, M., Oppezzo, P., Geffner, J., Bezares, R., Gamberale, R., Giordano, M.
(2008). Chronic Lymphocytic Leukemia Cells Bind and Present the Erythrocyte Protein Band 3: Possible Role as Initiators of Autoimmune Hemolytic Anemia. J. Immunol.
181: 3674-3683
[Abstract][Full Text]
Reinoso-Martin, C., Jantus-Lewintre, E., Ballesteros, C. G., Campos, C. B., Ferrer, J. R. M., Garcia-Conde, J.
(2008). ZAP-70 mRNA expression provides clinically valuable information in early-stage chronic lymphocytic leukemia. haematol
93: 1422-1424
[Full Text]
Kujawski, L., Ouillette, P., Erba, H., Saddler, C., Jakubowiak, A., Kaminski, M., Shedden, K., Malek, S. N.
(2008). Genomic complexity identifies patients with aggressive chronic lymphocytic leukemia. Blood
112: 1993-2003
[Abstract][Full Text]
Rassenti, L. Z., Jain, S., Keating, M. J., Wierda, W. G., Grever, M. R., Byrd, J. C., Kay, N. E., Brown, J. R., Gribben, J. G., Neuberg, D. S., He, F., Greaves, A. W., Rai, K. R., Kipps, T. J.
(2008). Relative value of ZAP-70, CD38, and immunoglobulin mutation status in predicting aggressive disease in chronic lymphocytic leukemia. Blood
112: 1923-1930
[Abstract][Full Text]
Tam, C. S., O'Brien, S., Wierda, W., Kantarjian, H., Wen, S., Do, K.-A., Thomas, D. A., Cortes, J., Lerner, S., Keating, M. J.
(2008). Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia. Blood
112: 975-980
[Abstract][Full Text]
Veldurthy, A., Patz, M., Hagist, S., Pallasch, C. P., Wendtner, C.-M., Hallek, M., Krause, G.
(2008). The kinase inhibitor dasatinib induces apoptosis in chronic lymphocytic leukemia cells in vitro with preference for a subgroup of patients with unmutated IgVH genes. Blood
112: 1443-1452
[Abstract][Full Text]
Rawstron, A. C., Bennett, F. L., O'Connor, S. J.M., Kwok, M., Fenton, J. A.L., Plummer, M., de Tute, R., Owen, R. G., Richards, S. J., Jack, A. S., Hillmen, P.
(2008). Monoclonal B-Cell Lymphocytosis and Chronic Lymphocytic Leukemia. NEJM
359: 575-583
[Abstract][Full Text]
Guarini, A., Chiaretti, S., Tavolaro, S., Maggio, R., Peragine, N., Citarella, F., Ricciardi, M. R., Santangelo, S., Marinelli, M., De Propris, M. S., Messina, M., Mauro, F. R., Del Giudice, I., Foa, R.
(2008). BCR ligation induced by IgM stimulation results in gene expression and functional changes only in IgVH unmutated chronic lymphocytic leukemia (CLL) cells. Blood
112: 782-792
[Abstract][Full Text]
Malavasi, F., Deaglio, S., Funaro, A., Ferrero, E., Horenstein, A. L., Ortolan, E., Vaisitti, T., Aydin, S.
(2008). Evolution and Function of the ADP Ribosyl Cyclase/CD38 Gene Family in Physiology and Pathology. Physiol. Rev.
88: 841-886
[Abstract][Full Text]
Li, F. J., Ding, S., Pan, J., Shakhmatov, M. A., Kashentseva, E., Wu, J., Li, Y., Soong, S.-j., Chiorazzi, N., Davis, R. S.
(2008). FCRL2 expression predicts IGHV mutation status and clinical progression in chronic lymphocytic leukemia. Blood
112: 179-187
[Abstract][Full Text]
Hallek, M., Cheson, B. D., Catovsky, D., Caligaris-Cappio, F., Dighiero, G., Dohner, H., Hillmen, P., Keating, M. J., Montserrat, E., Rai, K. R., Kipps, T. J.
(2008). Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood
111: 5446-5456
[Abstract][Full Text]
Aydin, S., Rossi, D., Bergui, L., D'Arena, G., Ferrero, E., Bonello, L., Omede, P., Novero, D., Morabito, F., Carbone, A., Gaidano, G., Malavasi, F., Deaglio, S.
(2008). CD38 gene polymorphism and chronic lymphocytic leukemia: a role in transformation to Richter syndrome?. Blood
111: 5646-5653
[Abstract][Full Text]
Mateo, G., Montalban, M. A., Vidriales, M.-B., Lahuerta, J. J., Mateos, M. V., Gutierrez, N., Rosinol, L., Montejano, L., Blade, J., Martinez, R., de la Rubia, J., Diaz-Mediavilla, J., Sureda, A., Ribera, J. M., Ojanguren, J. M., de Arriba, F., Palomera, L., Terol, M. J., Orfao, A., San Miguel, J. F.
(2008). Prognostic Value of Immunophenotyping in Multiple Myeloma: A Study by the PETHEMA/GEM Cooperative Study Groups on Patients Uniformly Treated With High-Dose Therapy. JCO
26: 2737-2744
[Abstract][Full Text]
Levin, S. E., Zhang, C., Kadlecek, T. A., Shokat, K. M., Weiss, A.
(2008). Inhibition of ZAP-70 Kinase Activity via an Analog-sensitive Allele Blocks T Cell Receptor and CD28 Superagonist Signaling. J. Biol. Chem.
283: 15419-15430
[Abstract][Full Text]
Friedrichs, B., Siegel, S., Kloess, M., Barsoum, A., Coggin, J. Jr., Rohrer, J., Jakob, I., Tiemann, M., Heidorn, K., Schulte, C., Kabelitz, D., Steinmann, J., Schmitz, N., Zeis, M.
(2008). Humoral Immune Responses against the Immature Laminin Receptor Protein Show Prognostic Significance in Patients with Chronic Lymphocytic Leukemia. J. Immunol.
180: 6374-6384
[Abstract][Full Text]
Hewamana, S., Alghazal, S., Lin, T. T., Clement, M., Jenkins, C., Guzman, M. L., Jordan, C. T., Neelakantan, S., Crooks, P. A., Burnett, A. K., Pratt, G., Fegan, C., Rowntree, C., Brennan, P., Pepper, C.
(2008). The NF-{kappa}B subunit Rel A is associated with in vitro survival and clinical disease progression in chronic lymphocytic leukemia and represents a promising therapeutic target. Blood
111: 4681-4689
[Abstract][Full Text]
Craig, F. E., Foon, K. A.
(2008). Flow cytometric immunophenotyping for hematologic neoplasms. Blood
111: 3941-3967
[Abstract][Full Text]
Cutrona, G., Colombo, M., Matis, S., Fabbi, M., Spriano, M., Callea, V., Vigna, E., Gentile, M., Zupo, S., Chiorazzi, N., Morabito, F., Ferrarini, M.
(2008). Clonal heterogeneity in chronic lymphocytic leukemia cells: superior response to surface IgM cross-linking in CD38, ZAP-70-positive cells. haematol
93: 413-422
[Abstract][Full Text]
Chen, L., Huynh, L., Apgar, J., Tang, L., Rassenti, L., Weiss, A., Kipps, T. J.
(2008). ZAP-70 enhances IgM signaling independent of its kinase activity in chronic lymphocytic leukemia. Blood
111: 2685-2692
[Abstract][Full Text]
Agrawal, S. G., Liu, F.-T., Wiseman, C., Shirali, S., Liu, H., Lillington, D., Du, M.-Q., Syndercombe-Court, D., Newland, A. C., Gribben, J. G., Jia, L.
(2008). Increased proteasomal degradation of Bax is a common feature of poor prognosis chronic lymphocytic leukemia. Blood
111: 2790-2796
[Abstract][Full Text]
Roos, G., Krober, A., Grabowski, P., Kienle, D., Buhler, A., Dohner, H., Rosenquist, R., Stilgenbauer, S.
(2008). Short telomeres are associated with genetic complexity, high-risk genomic aberrations, and short survival in chronic lymphocytic leukemia. Blood
111: 2246-2252
[Abstract][Full Text]
Poncet, D., Belleville, A., t'Kint de Roodenbeke, C., Roborel de Climens, A., Ben Simon, E., Merle-Beral, H., Callet-Bauchu, E., Salles, G., Sabatier, L., Delic, J., Gilson, E.
(2008). Changes in the expression of telomere maintenance genes suggest global telomere dysfunction in B-chronic lymphocytic leukemia. Blood
111: 2388-2391
[Abstract][Full Text]
Gachard, N., Salviat, A., Boutet, C., Arnoulet, C., Durrieu, F., Lenormand, B., Lepretre, S., Olschwang, S., Jardin, F., Lafage-Pochitaloff, M., Penther, D., Sainty, D., Reminieras, L., Feuillard, J., Bene, M. C., for the GEIL,
(2008). Multicenter study of ZAP-70 expression in patients with B-cell chronic lymphocytic leukemia using an optimized flow cytometry method. haematol
93: 215-223
[Abstract][Full Text]
Saddler, C., Ouillette, P., Kujawski, L., Shangary, S., Talpaz, M., Kaminski, M., Erba, H., Shedden, K., Wang, S., Malek, S. N.
(2008). Comprehensive biomarker and genomic analysis identifies p53 status as the major determinant of response to MDM2 inhibitors in chronic lymphocytic leukemia. Blood
111: 1584-1593
[Abstract][Full Text]
Longo, P. G., Laurenti, L., Gobessi, S., Sica, S., Leone, G., Efremov, D. G.
(2008). The Akt/Mcl-1 pathway plays a prominent role in mediating antiapoptotic signals downstream of the B-cell receptor in chronic lymphocytic leukemia B cells. Blood
111: 846-855
[Abstract][Full Text]
Gattei, V., Bulian, P., Del Principe, M. I., Zucchetto, A., Maurillo, L., Buccisano, F., Bomben, R., Dal-Bo, M., Luciano, F., Rossi, F. M., Degan, M., Amadori, S., Del Poeta, G.
(2008). Relevance of CD49d protein expression as overall survival and progressive disease prognosticator in chronic lymphocytic leukemia. Blood
111: 865-873
[Abstract][Full Text]
Hauswirth, A. W., Jager, U.
(2008). Impact of cytogenetic and molecular prognostic markers on the clinical management of chronic lymphocytic leukemia. haematol
93: 14-19
[Full Text]
Fernandez, V., Jares, P., Salaverria, I., Gine, E., Bea, S., Aymerich, M., Colomer, D., Villamor, N., Bosch, F., Montserrat, E., Campo, E.
(2008). Gene expression profile and genomic changes in disease progression of early-stage chronic lymphocytic leukemia. haematol
93: 132-136
[Abstract][Full Text]
Bosch, F., Ferrer, A., Villamor, N., Gonzalez, M., Briones, J., Gonzalez-Barca, E., Abella, E., Gardella, S., Escoda, L., Perez-Ceballos, E., Asensi, A., Sayas, M. J., Font, L., Altes, A., Muntanola, A., Bertazzoni, P., Rozman, M., Aymerich, M., Gine, E., Montserrat, E.
(2008). Fludarabine, Cyclophosphamide, and Mitoxantrone as Initial Therapy of Chronic Lymphocytic Leukemia: High Response Rate and Disease Eradication. Clin. Cancer Res.
14: 155-161
[Abstract][Full Text]
Gribben, J. G.
(2008). Molecular Profiling in CLL. ASH Education Book
2008: 444-449
[Abstract][Full Text]
Kipps, T. J.
(2008). Chronic Lymphocytic Leukemia: Prognostic Markers and Revised Criteria for Treatment and Response Assessment. Am Soc Clin Oncol Ed Book
2008: 286-290
[Abstract][Full Text]
Gribben, J. G.
(2008). The Role of Stem Cell Transplantation in Chronic Lymphocytic Leukemia. Am Soc Clin Oncol Ed Book
2008: 291-296
[Abstract][Full Text]
Deaglio, S., Vaisitti, T., Aydin, S., Bergui, L., D'Arena, G., Bonello, L., Omede, P., Scatolini, M., Jaksic, O., Chiorino, G., Efremov, D., Malavasi, F.
(2007). CD38 and ZAP-70 are functionally linked and mark CLL cells with high migratory potential. Blood
110: 4012-4021
[Abstract][Full Text]
Damle, R. N., Temburni, S., Calissano, C., Yancopoulos, S., Banapour, T., Sison, C., Allen, S. L., Rai, K. R., Chiorazzi, N.
(2007). CD38 expression labels an activated subset within chronic lymphocytic leukemia clones enriched in proliferating B cells. Blood
110: 3352-3359
[Abstract][Full Text]
Bras, M., Yuste, V. J., Roue, G., Barbier, S., Sancho, P., Virely, C., Rubio, M., Baudet, S., Esquerda, J. E., Merle-Beral, H., Sarfati, M., Susin, S. A.
(2007). Drp1 Mediates Caspase-Independent Type III Cell Death in Normal and Leukemic Cells. Mol. Cell. Biol.
27: 7073-7088
[Abstract][Full Text]
Tsimberidou, A. M., Wen, S., O'Brien, S., McLaughlin, P., Wierda, W. G., Ferrajoli, A., Faderl, S., Manning, J., Lerner, S., Mai, C. V., Rodriguez, A. M., Hess, M., Do, K.-A., Freireich, E. J., Kantarjian, H. M., Medeiros, L. J., Keating, M. J.
(2007). Assessment of Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma by Absolute Lymphocyte Counts in 2,126 Patients: 20 Years of Experience at The University of Texas M.D. Anderson Cancer Center. JCO
25: 4648-4656
[Abstract][Full Text]
Willimott, S., Baou, M., Huf, S., Deaglio, S., Wagner, S. D.
(2007). Regulation of CD38 in proliferating chronic lymphocytic leukemia cells stimulated with CD154 and interleukin-4. haematol
92: 1359-1366
[Abstract][Full Text]
Stamatopoulos, B., Meuleman, N., Haibe-Kains, B., Duvillier, H., Massy, M., Martiat, P., Bron, D., Lagneaux, L.
(2007). Quantification of ZAP70 mRNA in B Cells by Real-Time PCR Is a Powerful Prognostic Factor in Chronic Lymphocytic Leukemia. Clin. Chem.
53: 1757-1766
[Abstract][Full Text]
Abruzzo, L. V., Barron, L. L., Anderson, K., Newman, R. J., Wierda, W. G., O'Brien, S., Ferrajoli, A., Luthra, M., Talwalkar, S., Luthra, R., Jones, D., Keating, M. J., Coombes, K. R.
(2007). Identification and Validation of Biomarkers of IgVH Mutation Status in Chronic Lymphocytic Leukemia Using Microfluidics Quantitative Real-Time Polymerase Chain Reaction Technology. J. Mol. Diagn.
9: 546-555
[Abstract][Full Text]
Motiwala, T., Majumder, S., Kutay, H., Smith, D. S., Neuberg, D. S., Lucas, D. M., Byrd, J. C., Grever, M., Jacob, S. T.
(2007). Methylation and Silencing of Protein Tyrosine Phosphatase Receptor Type O in Chronic Lymphocytic Leukemia. Clin. Cancer Res.
13: 3174-3181
[Abstract][Full Text]
Sabattini, E., Orduz, R., Campidelli, C., Zinzani, P. L., Callea, V., Zupo, S., Cutrona, G., Morabito, F., Ferrarini, M., Pileri, S.
(2007). B cell chronic lymphocytic leukaemia/small lymphocytic lymphoma: role of ZAP70 determination on bone marrow biopsy specimens. J. Clin. Pathol.
60: 627-632
[Abstract][Full Text]
Josefsson, P., Geisler, C. H., Leffers, H., Petersen, J. H., Andersen, M. K., Jurlander, J., Buhl, A. M.
(2007). CLLU1 expression analysis adds prognostic information to risk prediction in chronic lymphocytic leukemia. Blood
109: 4973-4979
[Abstract][Full Text]
Wierda, W. G., O'Brien, S., Wang, X., Faderl, S., Ferrajoli, A., Do, K.-A., Cortes, J., Thomas, D., Garcia-Manero, G., Koller, C., Beran, M., Giles, F., Ravandi, F., Lerner, S., Kantarjian, H., Keating, M.
(2007). Prognostic nomogram and index for overall survival in previously untreated patients with chronic lymphocytic leukemia. Blood
109: 4679-4685
[Abstract][Full Text]
Fulci, V., Chiaretti, S., Goldoni, M., Azzalin, G., Carucci, N., Tavolaro, S., Castellano, L., Magrelli, A., Citarella, F., Messina, M., Maggio, R., Peragine, N., Santangelo, S., Mauro, F. R., Landgraf, P., Tuschl, T., Weir, D. B., Chien, M., Russo, J. J., Ju, J., Sheridan, R., Sander, C., Zavolan, M., Guarini, A., Foa, R., Macino, G.
(2007). Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia. Blood
109: 4944-4951
[Abstract][Full Text]
Ian Mockridge, C., Potter, K. N., Wheatley, I., Neville, L. A., Packham, G., Stevenson, F. K.
(2007). Reversible anergy of sIgM-mediated signaling in the two subsets of CLL defined by VH-gene mutational status. Blood
109: 4424-4431
[Abstract][Full Text]
Vallat, L. D., Park, Y., Li, C., Gribben, J. G.
(2007). Temporal genetic program following B-cell receptor cross-linking: altered balance between proliferation and death in healthy and malignant B cells. Blood
109: 3989-3997
[Abstract][Full Text]
Muntanola, A., Bosch, F., Arguis, P., Arellano-Rodrigo, E., Ayuso, C., Gine, E., Crespo, M., Abrisqueta, P., Moreno, C., Cobo, F., Lopez-Guillermo, A., Montserrat, E.
(2007). Abdominal Computed Tomography Predicts Progression in Patients With Rai Stage 0 Chronic Lymphocytic Leukemia. JCO
25: 1576-1580
[Abstract][Full Text]
Nowakowski, G. S., Hoyer, J. D., Shanafelt, T. D., Geyer, S. M., LaPlant, B. R., Call, T. G., Jelinek, D. F., Zent, C. S., Kay, N. E.
(2007). Using Smudge Cells on Routine Blood Smears to Predict Clinical Outcome in Chronic Lymphocytic Leukemia: A Universally Available Prognostic Test. Mayo Clin Proc.
82: 449-453
[Abstract][Full Text]
Bomben, R., Dal Bo, M., Capello, D., Benedetti, D., Marconi, D., Zucchetto, A., Forconi, F., Maffei, R., Ghia, E. M., Laurenti, L., Bulian, P., Del Principe, M. I., Palermo, G., Thorselius, M., Degan, M., Campanini, R., Guarini, A., Del Poeta, G., Rosenquist, R., Efremov, D. G., Marasca, R., Foa, R., Gaidano, G., Gattei, V.
(2007). Comprehensive characterization of IGHV3-21-expressing B-cell chronic lymphocytic leukemia: an Italian multicenter study. Blood
109: 2989-2998
[Abstract][Full Text]
O'Brien, S., Moore, J. O., Boyd, T. E., Larratt, L. M., Skotnicki, A., Koziner, B., Chanan-Khan, A. A., Seymour, J. F., Bociek, R. G., Pavletic, S., Rai, K. R.
(2007). Randomized Phase III Trial of Fludarabine Plus Cyclophosphamide With or Without Oblimersen Sodium (Bcl-2 antisense) in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia. JCO
25: 1114-1120
[Abstract][Full Text]
Grever, M. R., Lucas, D. M., Dewald, G. W., Neuberg, D. S., Reed, J. C., Kitada, S., Flinn, I. W., Tallman, M. S., Appelbaum, F. R., Larson, R. A., Paietta, E., Jelinek, D. F., Gribben, J. G., Byrd, J. C.
(2007). Comprehensive Assessment of Genetic and Molecular Features Predicting Outcome in Patients With Chronic Lymphocytic Leukemia: Results From the US Intergroup Phase III Trial E2997. JCO
25: 799-804
[Abstract][Full Text]
Gobessi, S., Laurenti, L., Longo, P. G., Sica, S., Leone, G., Efremov, D. G.
(2007). ZAP-70 enhances B-cell-receptor signaling despite absent or inefficient tyrosine kinase activation in chronic lymphocytic leukemia and lymphoma B cells. Blood
109: 2032-2039
[Abstract][Full Text]
Van Bockstaele, F., Pede, V., Janssens, A., Callewaert, F., Offner, F., Verhasselt, B., Philippe, J.
(2007). Lipoprotein Lipase mRNA Expression in Whole Blood Is a Prognostic Marker in B Cell Chronic Lymphocytic Leukemia. Clin. Chem.
53: 204-212
[Abstract][Full Text]
Venugopal, P., Gregory, S. A.
(2007). Lymphoproliferative disorders. ASH-SAP
2007: 265-297
[Full Text]
Chanan-Khan, A., Miller, K. C., Musial, L., Lawrence, D., Padmanabhan, S., Takeshita, K., Porter, C. W., Goodrich, D. W., Bernstein, Z. P., Wallace, P., Spaner, D., Mohr, A., Byrne, C., Hernandez-Ilizaliturri, F., Chrystal, C., Starostik, P., Czuczman, M. S.
(2006). Clinical Efficacy of Lenalidomide in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia: Results of a Phase II Study. JCO
24: 5343-5349
[Abstract][Full Text]
Coignet, J.-G., Padmanabhan, S., Manochakian, R., Miller, K. C., Wallace, P., Block, A., Chanan-Khan, A. A.
(2006). Co-Expression of CD38 with Zap-70 Is Predictive of Treatment Intervention in Patients (pts) with Early Stage Chronic Lymphocytic Leukemia (CLL).. ASH ANNUAL MEETING ABSTRACTS
108: 4945-4945
[Abstract]
Leong, A S-Y, Leong, T Y-M
(2006). Newer developments in immunohistology.. J. Clin. Pathol.
59: 1117-1126
[Abstract][Full Text]
Tinhofer, I., Rubenzer, G., Holler, C., Hofstaetter, E., Stoecher, M., Egle, A., Steurer, M., Greil, R.
(2006). Expression levels of CD38 in T cells predict course of disease in male patients with B-chronic lymphocytic leukemia. Blood
108: 2950-2956
[Abstract][Full Text]
Shanafelt, T. D., Witzig, T. E., Fink, S. R., Jenkins, R. B., Paternoster, S. F., Smoley, S. A., Stockero, K. J., Nast, D. M., Flynn, H. C., Tschumper, R. C., Geyer, S., Zent, C. S., Call, T. G., Jelinek, D. F., Kay, N. E., Dewald, G. W.
(2006). Prospective Evaluation of Clonal Evolution During Long-Term Follow-Up of Patients With Untreated Early-Stage Chronic Lymphocytic Leukemia. JCO
24: 4634-4641
[Abstract][Full Text]
Frey, U. H., Nuckel, H., Sellmann, L., Siemer, D., Kuppers, R., Durig, J., Duhrsen, U., Siffert, W.
(2006). The GNAS1 T393C Polymorphism Is Associated with Disease Progression and Survival in Chronic Lymphocytic Leukemia.. Clin. Cancer Res.
12: 5686-5692
[Abstract][Full Text]
Shanafelt, T. D., Byrd, J. C., Call, T. G., Zent, C. S., Kay, N. E.
(2006). Narrative review: initial management of newly diagnosed, early-stage chronic lymphocytic leukemia.. ANN INTERN MED
145: 435-447
[Abstract][Full Text]
Falini, B., Martelli, M. P., Bolli, N., Bonasso, R., Ghia, E., Pallotta, M. T., Diverio, D., Nicoletti, I., Pacini, R., Tabarrini, A., Galletti, B. V., Mannucci, R., Roti, G., Rosati, R., Specchia, G., Liso, A., Tiacci, E., Alcalay, M., Luzi, L., Volorio, S., Bernard, L., Guarini, A., Amadori, S., Mandelli, F., Pane, F., Lo-Coco, F., Saglio, G., Pelicci, P.-G., Martelli, M. F., Mecucci, C., for the GIMEMA Acute Leukemia Working Party,
(2006). Immunohistochemistry predicts nucleophosmin (NPM) mutations in acute myeloid leukemia. Blood
108: 1999-2005
[Abstract][Full Text]
Deaglio, S., Vaisitti, T., Aydin, S., Ferrero, E., Malavasi, F.
(2006). In-tandem insight from basic science combined with clinical research: CD38 as both marker and key component of the pathogenetic network underlying chronic lymphocytic leukemia. Blood
108: 1135-1144
[Abstract][Full Text]
Lin, K., Glenn, M. A., Harris, R. J., Duckworth, A. D., Dennett, S., Cawley, J. C., Zuzel, M., Slupsky, J. R.
(2006). c-Abl Expression in Chronic Lymphocytic Leukemia Cells: Clinical and Therapeutic Implications.. Cancer Res.
66: 7801-7809
[Abstract][Full Text]
Yee, K. W. L., O'Brien, S. M.
(2006). Chronic Lymphocytic Leukemia: Diagnosis and Treatment. Mayo Clin Proc.
81: 1105-1129
[Abstract][Full Text]
Del Principe, M. I., Del Poeta, G., Buccisano, F., Maurillo, L., Venditti, A., Zucchetto, A., Marini, R., Niscola, P., Consalvo, M. A. I., Mazzone, C., Ottaviani, L., Panetta, P., Bruno, A., Bomben, R., Suppo, G., Degan, M., Gattei, V., de Fabritiis, P., Cantonetti, M., Lo Coco, F., Del Principe, D., Amadori, S.
(2006). Clinical significance of ZAP-70 protein expression in B-cell chronic lymphocytic leukemia. Blood
108: 853-861
[Abstract][Full Text]
Koller, C., Bekele, B. N., Zhou, X., Park, C., Estrov, Z., O'Brien, S., Keating, M., Jilani, I., Giles, F. J., Kantarjian, H. M., Albitar, M.
(2006). Plasma thrombopoietin compared with immunoglobulin heavy-chain mutation status as a predictor of survival in chronic lymphocytic leukemia. Blood
108: 1001-1006
[Abstract][Full Text]
Deglesne, P.-A., Chevallier, N., Letestu, R., Baran-Marszak, F., Beitar, T., Salanoubat, C., Sanhes, L., Nataf, J., Roger, C., Varin-Blank, N., Ajchenbaum-Cymbalista, F.
(2006). Survival response to B-cell receptor ligation is restricted to progressive chronic lymphocytic leukemia cells irrespective of zap70 expression.. Cancer Res.
66: 7158-7166
[Abstract][Full Text]
Krober, A., Dohner, H., Stilgenbauer, S.
(2006). In Reply. JCO
24: 3219-3220
[Full Text]
Tsimberidou, A.-M., O'Brien, S., Khouri, I., Giles, F. J., Kantarjian, H. M., Champlin, R., Wen, S., Do, K.-A., Smith, S. C., Lerner, S., Freireich, E. J., Keating., M. J.
(2006). Clinical Outcomes and Prognostic Factors in Patients With Richter's Syndrome Treated With Chemotherapy or Chemoimmunotherapy With or Without Stem-Cell Transplantation. JCO
24: 2343-2351
[Abstract][Full Text]
Secchiero, P., Barbarotto, E., Tiribelli, M., Zerbinati, C., di Iasio, M. G., Gonelli, A., Cavazzini, F., Campioni, D., Fanin, R., Cuneo, A., Zauli, G.
(2006). Functional integrity of the p53-mediated apoptotic pathway induced by the nongenotoxic agent nutlin-3 in B-cell chronic lymphocytic leukemia (B-CLL). Blood
107: 4122-4129
[Abstract][Full Text]
Richardson, S. J., Matthews, C., Catherwood, M. A., Alexander, H. D., Carey, B. S., Farrugia, J., Gardiner, A., Mould, S., Oscier, D., Copplestone, J. A., Prentice, A. G.
(2006). ZAP-70 expression is associated with enhanced ability to respond to migratory and survival signals in B-cell chronic lymphocytic leukemia (B-CLL). Blood
107: 3584-3592
[Abstract][Full Text]
de Totero, D., Meazza, R., Zupo, S., Cutrona, G., Matis, S., Colombo, M., Balleari, E., Pierri, I., Fabbi, M., Capaia, M., Azzarone, B., Gobbi, M., Ferrarini, M., Ferrini, S.
(2006). Interleukin-21 receptor (IL-21R) is up-regulated by CD40 triggering and mediates proapoptotic signals in chronic lymphocytic leukemia B cells. Blood
107: 3708-3715
[Abstract][Full Text]
Hus, I., Podhorecka, M., Bojarska-Junak, A., Rolinski, J., Schmitt, M., Sieklucka, M., Wasik-Szczepanek, E., Dmoszynska, A.
(2006). The clinical significance of ZAP-70 and CD38 expression in B-cell chronic lymphocytic leukaemia. Ann Oncol
17: 683-690
[Abstract][Full Text]
Potter, K. N., Mockridge, C. I., Neville, L., Wheatley, I., Schenk, M., Orchard, J., Duncombe, A. S., Packham, G., Stevenson, F. K.
(2006). Structural and Functional Features of the B-Cell Receptor in IgG-Positive Chronic Lymphocytic Leukemia.. Clin. Cancer Res.
12: 1672-1679
[Abstract][Full Text]
Krober, A., Bloehdorn, J., Hafner, S., Buhler, A., Seiler, T., Kienle, D., Winkler, D., Bangerter, M., Schlenk, R. F., Benner, A., Lichter, P., Dohner, H., Stilgenbauer, S.
(2006). Additional Genetic High-Risk Features Such As 11q Deletion, 17p Deletion, and V3-21 Usage Characterize Discordance of ZAP-70 and VH Mutation Status in Chronic Lymphocytic Leukemia. JCO
24: 969-975
[Abstract][Full Text]