When chronic lymphocytic leukemia (CLL) was last reviewed inthe Journal,1 it was considered a homogeneous disease of immature,immune-incompetent, minimally self-renewing B cells,2 whichaccumulate relentlessly because of a faulty apoptotic mechanism.3In the past decade, these views have been transformed by a wealthof new information about the leukemic cells. CLL is now viewedas two related entities, both originating from antigen-stimulatedmature B lymphocytes, which either avoid death through the intercessionof external signals or die by apoptosis, only to be replenishedby proliferating precursor cells (Table 1).
View this table: [in this window]
[in a new window]
The Biology of Leukemic Lymphocytes and the Clinical Course of CLL
Inducing Factors in CLL
Promoting Factors in CLL
Inferring the Role of Antigenic Stimulation from B-Cell Receptors
Signal Transduction after Antigen Engagement
Consequences of Signal Transduction through the B-Cell Receptor
Signals from the Microenvironment
Appearance and Evolution of New Genetic Mutations
A Unifying Hypothesis for the Development, Growth, and Evolution of CLL
Growth and Evolution of CLL Cells
Development of CLL from Normal B Lymphocytes
From Which Subpopulation Do CLL Cells Develop?
Clinical Implications
Prognosis
Management
New Therapeutic Approaches
Source Information
From the Institute for Medical Research, North Shore–LIJ Health System (N.C., K.R.R.), and the Departments of Medicine, North Shore University Hospital, Manhasset, N.Y., and New York University School of Medicine, New York (N.C.); the Departments of Medicine, Long Island Jewish Medical Center, New Hyde Park, N.Y., and Albert Einstein School of Medicine, Bronx, N.Y. (K.R.R.); and the Division of Medical Oncology C, Istituto Nazionale per la Ricerca sul Cancro, and the Dipartimento di Oncologia Clinica e Sperimentale, Universitá di Genova — both in Genoa, Italy (M.F.).
Address reprint requests to Dr. Chiorazzi at the Institute for Medical Research, North Shore–LIJ Health System, 350 Community Dr., Manhasset, NY 11030, or at nchizzi@nshs.edu.
This article has been cited by other articles:
Tsai, H.-T., Caporaso, N. E., Kyle, R. A., Katzmann, J. A., Dispenzieri, A., Hayes, R. B., Marti, G. E., Albitar, M., Ghia, P., Rajkumar, S. V., Landgren, O.
(2009). Evidence of serum immunoglobulin abnormalities up to 9.8 years before diagnosis of chronic lymphocytic leukemia: a prospective study. Blood
114: 4928-4932
[Abstract][Full Text]
Delgado, J., Pillai, S., Phillips, N., Brunet, S., Pratt, G., Briones, J., Lovell, R., Martino, R., Ewing, J., Sureda, A., Milligan, D. W., Sierra, J.
(2009). Does reduced-intensity allogeneic transplantation confer a survival advantage to patients with poor prognosis chronic lymphocytic leukaemia? A case-control retrospective analysis. Ann Oncol
20: 2007-2012
[Abstract][Full Text]
Loeder, S., Zenz, T., Schnaiter, A., Mertens, D., Winkler, D., Dohner, H., Debatin, K.-M., Stilgenbauer, S., Fulda, S.
(2009). A Novel Paradigm to Trigger Apoptosis in Chronic Lymphocytic Leukemia. Cancer Res.
69: 8977-8986
[Abstract][Full Text]
Calin, G. A., Croce, C. M.
(2009). Chronic lymphocytic leukemia: interplay between noncoding RNAs and protein-coding genes. Blood
114: 4761-4770
[Abstract][Full Text]
Calissano, C., Damle, R. N., Hayes, G., Murphy, E. J., Hellerstein, M. K., Moreno, C., Sison, C., Kaufman, M. S., Kolitz, J. E., Allen, S. L., Rai, K. R., Chiorazzi, N.
(2009). In vivo intraclonal and interclonal kinetic heterogeneity in B-cell chronic lymphocytic leukemia. Blood
114: 4832-4842
[Abstract][Full Text]
Kubagawa, H., Oka, S., Kubagawa, Y., Torii, I., Takayama, E., Kang, D.-W., Gartland, G. L., Bertoli, L. F., Mori, H., Takatsu, H., Kitamura, T., Ohno, H., Wang, J.-Y.
(2009). Identity of the elusive IgM Fc receptor (Fc{micro}R) in humans. JEM
206: 2779-2793
[Abstract][Full Text]
Baskar, S., Suschak, J. M., Samija, I., Srinivasan, R., Childs, R. W., Pavletic, S. Z., Bishop, M. R., Rader, C.
(2009). A human monoclonal antibody drug and target discovery platform for B-cell chronic lymphocytic leukemia based on allogeneic hematopoietic stem cell transplantation and phage display. Blood
114: 4494-4502
[Abstract][Full Text]
Sutton, L.-A., Kostareli, E., Hadzidimitriou, A., Darzentas, N., Tsaftaris, A., Anagnostopoulos, A., Rosenquist, R., Stamatopoulos, K.
(2009). Extensive intraclonal diversification in a subgroup of chronic lymphocytic leukemia patients with stereotyped IGHV4-34 receptors: implications for ongoing interactions with antigen. Blood
114: 4460-4468
[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]
Stamatopoulos, K.
(2009). CLL: promiscuity leads to risks. Blood
114: 3508-3509
[Full Text]
Seiler, T., Woelfle, M., Yancopoulos, S., Catera, R., Li, W., Hatzi, K., Moreno, C., Torres, M., Paul, S., Dohner, H., Stilgenbauer, S., Kaufman, M. S., Kolitz, J. E., Allen, S. L., Rai, K. R., Chu, C. C., Chiorazzi, N.
(2009). Characterization of structurally defined epitopes recognized by monoclonal antibodies produced by chronic lymphocytic leukemia B cells. Blood
114: 3615-3624
[Abstract][Full Text]
Burger, J. A., Ghia, P., Rosenwald, A., Caligaris-Cappio, F.
(2009). The microenvironment in mature B-cell malignancies: a target for new treatment strategies. Blood
114: 3367-3375
[Abstract][Full Text]
Abrisqueta, P., Pereira, A., Rozman, C., Aymerich, M., Gine, E., Moreno, C., Muntanola, A., Rozman, M., Villamor, N., Hodgson, K., Campo, E., Bosch, F., Montserrat, E.
(2009). Improving survival in patients with chronic lymphocytic leukemia (1980-2008): the Hospital Clinic of Barcelona experience. Blood
114: 2044-2050
[Abstract][Full Text]
Salerno, E., Scaglione, B. J., Coffman, F. D., Brown, B. D., Baccarini, A., Fernandes, H., Marti, G., Raveche, E. S.
(2009). Correcting miR-15a/16 genetic defect in New Zealand Black mouse model of CLL enhances drug sensitivity. Molecular Cancer Therapeutics
8: 2684-2692
[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]
Steele, A. J., Prentice, A. G., Hoffbrand, A. V., Yogashangary, B. C., Hart, S. M., Lowdell, M. W., Samuel, E. R., North, J. M., Nacheva, E. P., Chanalaris, A., Kottaridis, P., Cwynarski, K., Wickremasinghe, R. G.
(2009). 2-phenylacetylenesulfonamide (PAS) induces p53-independent apoptotic killing of B-chronic lymphocytic leukemia (CLL) cells. Blood
114: 1217-1225
[Abstract][Full Text]
Quiroga, M. P., Balakrishnan, K., Kurtova, A. V., Sivina, M., Keating, M. J., Wierda, W. G., Gandhi, V., Burger, J. A.
(2009). B-cell antigen receptor signaling enhances chronic lymphocytic leukemia cell migration and survival: specific targeting with a novel spleen tyrosine kinase inhibitor, R406. Blood
114: 1029-1037
[Abstract][Full Text]
Hanlon, K., Ellard, S., Rudin, C. E., Thorne, S., Davies, T., Harries, L. W.
(2009). Evaluation of 13q14 Status in Patients with Chronic Lymphocytic Leukemia Using Single Nucleotide Polymorphism-Based Techniques. J. Mol. Diagn.
11: 298-305
[Abstract][Full Text]
Rossi, D., Spina, V., Cerri, M., Rasi, S., Deambrogi, C., De Paoli, L., Laurenti, L., Maffei, R., Forconi, F., Bertoni, F., Zucca, E., Agostinelli, C., Cabras, A., Lucioni, M., Martini, M., Magni, M., Deaglio, S., Ladetto, M., Nomdedeu, J. F., Besson, C., Ramponi, A., Canzonieri, V., Paulli, M., Marasca, R., Larocca, L. M., Carbone, A., Pileri, S. A., Gattei, V., Gaidano, G.
(2009). Stereotyped B-Cell Receptor Is an Independent Risk Factor of Chronic Lymphocytic Leukemia Transformation to Richter Syndrome. Clin. Cancer Res.
15: 4415-4422
[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]
Deaglio, S., Malavasi, F.
(2009). Chronic lymphocytic leukemia microenvironment: shifting the balance from apoptosis to proliferation. haematol
94: 752-756
[Full Text]
Niedermeier, M., Hennessy, B. T., Knight, Z. A., Henneberg, M., Hu, J., Kurtova, A. V., Wierda, W. G., Keating, M. J., Shokat, K. M., Burger, J. A.
(2009). Isoform-selective phosphoinositide 3'-kinase inhibitors inhibit CXCR4 signaling and overcome stromal cell-mediated drug resistance in chronic lymphocytic leukemia: a novel therapeutic approach. Blood
113: 5549-5557
[Abstract][Full Text]
Chen, R., Wierda, W. G., Chubb, S., Hawtin, R. E., Fox, J. A., Keating, M. J., Gandhi, V., Plunkett, W.
(2009). Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood
113: 4637-4645
[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]
Burger, J. A., Quiroga, M. P., Hartmann, E., Burkle, A., Wierda, W. G., Keating, M. J., Rosenwald, A.
(2009). High-level expression of the T-cell chemokines CCL3 and CCL4 by chronic lymphocytic leukemia B cells in nurselike cell cocultures and after BCR stimulation. Blood
113: 3050-3058
[Abstract][Full Text]
Holler, C., Pinon, J. D., Denk, U., Heyder, C., Hofbauer, S., Greil, R., Egle, A.
(2009). PKC{beta} is essential for the development of chronic lymphocytic leukemia in the TCL1 transgenic mouse model: validation of PKC{beta} as a therapeutic target in chronic lymphocytic leukemia. Blood
113: 2791-2794
[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]
Caligaris-Cappio, F.
(2009). ROMA illuminates CLL genomic lesions. Blood
113: 1209-1210
[Full Text]
Grubor, V., Krasnitz, A., Troge, J. E., Meth, J. L., Lakshmi, B., Kendall, J. T., Yamrom, B., Alex, G., Pai, D., Navin, N., Hufnagel, L. A., Lee, Y.-H., Cook, K., Allen, S. L., Rai, K. R., Damle, R. N., Calissano, C., Chiorazzi, N., Wigler, M., Esposito, D.
(2009). Novel genomic alterations and clonal evolution in chronic lymphocytic leukemia revealed by representational oligonucleotide microarray analysis (ROMA). Blood
113: 1294-1303
[Abstract][Full Text]
BOELENS, J., LUST, S., VANHOECKE, B., OFFNER, F.
(2009). Chronic Lymphocytic Leukaemia. Anticancer Res
29: 605-615
[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]
Hadzidimitriou, A., Darzentas, N., Murray, F., Smilevska, T., Arvaniti, E., Tresoldi, C., Tsaftaris, A., Laoutaris, N., Anagnostopoulos, A., Davi, F., Ghia, P., Rosenquist, R., Stamatopoulos, K., Belessi, C.
(2009). Evidence for the significant role of immunoglobulin light chains in antigen recognition and selection in chronic lymphocytic leukemia. Blood
113: 403-411
[Abstract][Full Text]
Balakrishnan, K., Burger, J. A., Wierda, W. G., Gandhi, V.
(2009). AT-101 induces apoptosis in CLL B cells and overcomes stromal cell-mediated Mcl-1 induction and drug resistance. Blood
113: 149-153
[Abstract][Full Text]
Enjuanes, A., Benavente, Y., Bosch, F., Martin-Guerrero, I., Colomer, D., Perez-Alvarez, S., Reina, O., Ardanaz, M. T., Jares, P., Garcia-Orad, A., Pujana, M. A., Montserrat, E., de Sanjose, S., Campo, E.
(2008). Genetic Variants in Apoptosis and Immunoregulation-Related Genes Are Associated with Risk of Chronic Lymphocytic Leukemia. Cancer Res.
68: 10178-10186
[Abstract][Full Text]
Bekeredjian-Ding, I., Doster, A., Schiller, M., Heyder, P., Lorenz, H.-M., Schraven, B., Bommhardt, U., Heeg, K.
(2008). TLR9-Activating DNA Up-Regulates ZAP70 via Sustained PKB Induction in IgM+ B Cells. J. Immunol.
181: 8267-8277
[Abstract][Full Text]
Hegde, G. V., Peterson, K. J., Emanuel, K., Mittal, A. K., Joshi, A. D., Dickinson, J. D., Kollessery, G. J., Bociek, R. G., Bierman, P., Vose, J. M., Weisenburger, D. D., Joshi, S. S.
(2008). Hedgehog-Induced Survival of B-Cell Chronic Lymphocytic Leukemia Cells in a Stromal Cell Microenvironment: A Potential New Therapeutic Target. Mol Cancer Res
6: 1928-1936
[Abstract][Full Text]
Roue, G., Lopez-Guerra, M., Milpied, P., Perez-Galan, P., Villamor, N., Montserrat, E., Campo, E., Colomer, D.
(2008). Bendamustine Is Effective in p53-Deficient B-Cell Neoplasms and Requires Oxidative Stress and Caspase-Independent Signaling. Clin. Cancer Res.
14: 6907-6915
[Abstract][Full Text]
Steele, A. J., Prentice, A. G., Hoffbrand, A. V., Yogashangary, B. C., Hart, S. M., Nacheva, E. P., Howard-Reeves, J. D., Duke, V. M., Kottaridis, P. D., Cwynarski, K., Vassilev, L. T., Wickremasinghe, R. G.
(2008). p53-mediated apoptosis of CLL cells: evidence for a transcription-independent mechanism. Blood
112: 3827-3834
[Abstract][Full Text]
Zenz, T., Krober, A., Scherer, K., Habe, S., Buhler, A., Benner, A., Denzel, T., Winkler, D., Edelmann, J., Schwanen, C., Dohner, H., Stilgenbauer, S.
(2008). Monoallelic TP53 inactivation is associated with poor prognosis in chronic lymphocytic leukemia: results from a detailed genetic characterization with long-term follow-up. Blood
112: 3322-3329
[Abstract][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]
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]
Herbst, C., Monsef, I., Skoetz, N., Engert, A.
(2008). Eighth Biannual Report of the Cochrane Haematological Malignancies Group--Focus on Chronic Lymphatic Leukemia. JNCI J Natl Cancer Inst
100: E1-E1
[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]
Nowakowski, G. S.
(2008). Gang of 3 in aggressive CLL?. Blood
112: 5-6
[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]
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]
Lanemo Myhrinder, A., Hellqvist, E., Sidorova, E., Soderberg, A., Baxendale, H., Dahle, C., Willander, K., Tobin, G., Backman, E., Soderberg, O., Rosenquist, R., Horkko, S., Rosen, A.
(2008). A new perspective: molecular motifs on oxidized LDL, apoptotic cells, and bacteria are targets for chronic lymphocytic leukemia antibodies. Blood
111: 3838-3848
[Abstract][Full Text]
Dillman, R. O.
(2008). Immunophenotyping of Chronic Lymphoid Leukemias. JCO
26: 1193-1194
[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]
Ouillette, P., Erba, H., Kujawski, L., Kaminski, M., Shedden, K., Malek, S. N.
(2008). Integrated Genomic Profiling of Chronic Lymphocytic Leukemia Identifies Subtypes of Deletion 13q14. Cancer Res.
68: 1012-1021
[Abstract][Full Text]
Murray, F., Darzentas, N., Hadzidimitriou, A., Tobin, G., Boudjogra, M., Scielzo, C., Laoutaris, N., Karlsson, K., Baran-Marzsak, F., Tsaftaris, A., Moreno, C., Anagnostopoulos, A., Caligaris-Cappio, F., Vaur, D., Ouzounis, C., Belessi, C., Ghia, P., Davi, F., Rosenquist, R., Stamatopoulos, K.
(2008). Stereotyped patterns of somatic hypermutation in subsets of patients with chronic lymphocytic leukemia: implications for the role of antigen selection in leukemogenesis. Blood
111: 1524-1533
[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]
Visco, C., Ruggeri, M., Laura Evangelista, M., Stasi, R., Zanotti, R., Giaretta, I., Ambrosetti, A., Madeo, D., Pizzolo, G., Rodeghiero, F.
(2008). Impact of immune thrombocytopenia on the clinical course of chronic lymphocytic leukemia. Blood
111: 1110-1116
[Abstract][Full Text]
de Totero, D., Meazza, R., Capaia, M., Fabbi, M., Azzarone, B., Balleari, E., Gobbi, M., Cutrona, G., Ferrarini, M., Ferrini, S.
(2008). The opposite effects of IL-15 and IL-21 on CLL B cells correlate with differential activation of the JAK/STAT and ERK1/2 pathways. Blood
111: 517-524
[Abstract][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]
Santidrian, A. F., Cosialls, A. M., Coll-Mulet, L., Iglesias-Serret, D., de Frias, M., Gonzalez-Girones, D. M., Campas, C., Domingo, A., Pons, G., Gil, J.
(2007). The potential anticancer agent PK11195 induces apoptosis irrespective of p53 and ATM status in chronic lymphocytic leukemia cells. haematol
92: 1631-1638
[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]
Backman, E., Bergh, A.-C., Lagerdahl, I., Rydberg, B., Sundstrom, C., Tobin, G., Rosenquist, R., Linderholm, M., Rosen, A.
(2007). Thioredoxin, produced by stromal cells retrieved from the lymph node microenvironment, rescues chronic lymphocytic leukemia cells from apoptosis in vitro. haematol
92: 1495-1504
[Abstract][Full Text]
Burkle, A., Niedermeier, M., Schmitt-Graff, A., Wierda, W. G., Keating, M. J., Burger, J. A.
(2007). Overexpression of the CXCR5 chemokine receptor, and its ligand, CXCL13 in B-cell chronic lymphocytic leukemia. Blood
110: 3316-3325
[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]
Joshi, A. D., Hegde, G. V., Dickinson, J. D., Mittal, A. K., Lynch, J. C., Eudy, J. D., Armitage, J. O., Bierman, P. J., Bociek, R. G., Devetten, M. P., Vose, J. M., Joshi, S. S.
(2007). ATM, CTLA4, MNDA, and HEM1 in High versus Low CD38 Expressing B-Cell Chronic Lymphocytic Leukemia. Clin. Cancer Res.
13: 5295-5304
[Abstract][Full Text]
Stilgenbauer, S., Sander, S., Bullinger, L., Benner, A., Leupolt, E., Winkler, D., Krober, A., Kienle, D., Lichter, P., Dohner, H.
(2007). Clonal evolution in chronic lymphocytic leukemia: acquisition of high-risk genomic aberrations associated with unmutated VH, resistance to therapy, and short survival. haematol
92: 1242-1245
[Abstract][Full Text]
Lech-Maranda, E., Juszczynski, P., Szmigielska-Kaplon, A., Jamroziak, K., Balcerczak, E., Robak, T.
(2007). Human leukocyte antigens HLA DRB1 influence clinical outcome of chronic lymphocytic leukemia. haematol
92: 710-711
[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]
Ocana, E., Delgado-Perez, L., Campos-Caro, A., Munoz, J., Paz, A., Franco, R., Brieva, J. A.
(2007). The prognostic role of CXCR3 expression by chronic lymphocytic leukemia B cells. haematol
92: 349-356
[Abstract][Full Text]
Landgren, O., Rapkin, J. S., Caporaso, N. E., Mellemkjaer, L., Gridley, G., Goldin, L. R., Engels, E. A.
(2007). Respiratory tract infections and subsequent risk of chronic lymphocytic leukemia. Blood
109: 2198-2201
[Abstract][Full Text]
Smit, L. A., Hallaert, D. Y.H., Spijker, R., de Goeij, B., Jaspers, A., Kater, A. P., van Oers, M. H.J., van Noesel, C. J.M., Eldering, E.
(2007). Differential Noxa/Mcl-1 balance in peripheral versus lymph node chronic lymphocytic leukemia cells correlates with survival capacity. Blood
109: 1660-1668
[Abstract][Full Text]
Volkheimer, A. D., Weinberg, J. B., Beasley, B. E., Whitesides, J. F., Gockerman, J. P., Moore, J. O., Kelsoe, G., Goodman, B. K., Levesque, M. C.
(2007). Progressive immunoglobulin gene mutations in chronic lymphocytic leukemia: evidence for antigen-driven intraclonal diversification. Blood
109: 1559-1567
[Abstract][Full Text]
Stamatopoulos, K., Belessi, C., Moreno, C., Boudjograh, M., Guida, G., Smilevska, T., Belhoul, L., Stella, S., Stavroyianni, N., Crespo, M., Hadzidimitriou, A., Sutton, L., Bosch, F., Laoutaris, N., Anagnostopoulos, A., Montserrat, E., Fassas, A., Dighiero, G., Caligaris-Cappio, F., Merle-Beral, H., Ghia, P., Davi, F.
(2007). Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: pathogenetic implications and clinical correlations. Blood
109: 259-270
[Abstract][Full Text]
Moufarij, M. A., Sampath, D., Keating, M. J., Plunkett, W.
(2006). Fludarabine increases oxaliplatin cytotoxicity in normal and chronic lymphocytic leukemia lymphocytes by suppressing interstrand DNA crosslink removal. Blood
108: 4187-4193
[Abstract][Full Text]
Barragan, M., de Frias, M., Iglesias-Serret, D., Campas, C., Castano, E., Santidrian, A. F., Coll-Mulet, L., Cosialls, A. M., Domingo, A., Pons, G., Gil, J.
(2006). Regulation of Akt/PKB by phosphatidylinositol 3-kinase-dependent and -independent pathways in B-cell chronic lymphocytic leukemia cells: role of protein kinase C{beta}. J. Leukoc. Biol.
80: 1473-1479
[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]
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]
Yan, X.-j., Albesiano, E., Zanesi, N., Yancopoulos, S., Sawyer, A., Romano, E., Petlickovski, A., Efremov, D. G., Croce, C. M., Chiorazzi, N.
(2006). B cell receptors in TCL1 transgenic mice resemble those of aggressive, treatment-resistant human chronic lymphocytic leukemia. Proc. Natl. Acad. Sci. USA
103: 11713-11718
[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]
Landgren, O., Engels, E. A., Caporaso, N. E., Gridley, G., Mellemkjaer, L., Hemminki, K., Linet, M. S., Goldin, L. R.
(2006). Patterns of autoimmunity and subsequent chronic lymphocytic leukemia in Nordic countries. Blood
108: 292-296
[Abstract][Full Text]
Coll-Mulet, L., Iglesias-Serret, D., Santidrian, A. F., Cosialls, A. M., de Frias, M., Castano, E., Campas, C., Barragan, M., de Sevilla, A. F., Domingo, A., Vassilev, L. T., Pons, G., Gil, J.
(2006). MDM2 antagonists activate p53 and synergize with genotoxic drugs in B-cell chronic lymphocytic leukemia cells. Blood
107: 4109-4114
[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]
Khan, I. H., Mendoza, S., Rhyne, P., Ziman, M., Tuscano, J., Eisinger, D., Kung, H.-J., Luciw, P. A.
(2006). Multiplex Analysis of Intracellular Signaling Pathways in Lymphoid Cells by Microbead Suspension Arrays. Mol. Cell. Proteomics
5: 758-768
[Abstract][Full Text]
Caligaris-Cappio, F.
(2006). A novel gene for an old disease. Blood
107: 2594-2594
[Full Text]
Thorselius, M., Krober, A., Murray, F., Thunberg, U., Tobin, G., Buhler, A., Kienle, D., Albesiano, E., Maffei, R., Dao-Ung, L.-P., Wiley, J., Vilpo, J., Laurell, A., Merup, M., Roos, G., Karlsson, K., Chiorazzi, N., Marasca, R., Dohner, H., Stilgenbauer, S., Rosenquist, R.
(2006). Strikingly homologous immunoglobulin gene rearrangements and poor outcome in VH3-21-using chronic lymphocytic leukemia patients independent of geographic origin and mutational status. Blood
107: 2889-2894
[Abstract][Full Text]
Kienle, D., Benner, A., Krober, A., Winkler, D., Mertens, D., Buhler, A., Seiler, T., Jager, U., Lichter, P., Dohner, H., Stilgenbauer, S.
(2006). Distinct gene expression patterns in chronic lymphocytic leukemia defined by usage of specific VH genes. Blood
107: 2090-2093
[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]
Montserrat, E., Moreno, C., Esteve, J., Urbano-Ispizua, A., Gine, E., Bosch, F.
(2006). How I treat refractory CLL. Blood
107: 1276-1283
[Abstract][Full Text]
Anichini, A., Mortarini, R., Romagnoli, L., Baldassari, P., Cabras, A., Carlo-Stella, C., Gianni, A. M., Di Nicola, M.
(2006). Skewed T-cell differentiation in patients with indolent non-Hodgkin lymphoma reversed by ex vivo T-cell culture with {gamma}c cytokines. Blood
107: 602-609
[Abstract][Full Text]
Smedby, K. E., Hjalgrim, H., Askling, J., Chang, E. T., Gregersen, H., Porwit-MacDonald, A., Sundstrom, C., Akerman, M., Melbye, M., Glimelius, B., Adami, H.-O.
(2006). Autoimmune and Chronic Inflammatory Disorders and Risk of Non-Hodgkin Lymphoma by Subtype. JNCI J Natl Cancer Inst
98: 51-60
[Abstract][Full Text]
Chiorazzi, N., Ferrarini, M.
(2006). Evolving View of the In-Vivo Kinetics of Chronic Lymphocytic Leukemia B Cells. ASH Education Book
2006: 273-278
[Abstract][Full Text]
Morton, L. M., Wang, S. S., Devesa, S. S., Hartge, P., Weisenburger, D. D., Linet, M. S.
(2006). Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001. Blood
107: 265-276
[Abstract][Full Text]
Ye, M., Ermakova, O., Graf, T.
(2005). PU.1 is not strictly required for B cell development and its absence induces a B-2 to B-1 cell switch. JEM
202: 1411-1422
[Abstract][Full Text]
Nabhan, C., Bitran, J. D.
(2005). Chronic Lymphocytic Leukemia: To Transplant or Not to Transplant... That Is the Question?. JCO
23: 8126-8127
[Full Text]
Calin, G. A., Ferracin, M., Cimmino, A., Di Leva, G., Shimizu, M., Wojcik, S. E., Iorio, M. V., Visone, R., Sever, N. I., Fabbri, M., Iuliano, R., Palumbo, T., Pichiorri, F., Roldo, C., Garzon, R., Sevignani, C., Rassenti, L., Alder, H., Volinia, S., Liu, C.-g., Kipps, T. J., Negrini, M., Croce, C. M.
(2005). A MicroRNA Signature Associated with Prognosis and Progression in Chronic Lymphocytic Leukemia. NEJM
353: 1793-1801
[Abstract][Full Text]
Chen, R., Keating, M. J., Gandhi, V., Plunkett, W.
(2005). Transcription inhibition by flavopiridol: mechanism of chronic lymphocytic leukemia cell death. Blood
106: 2513-2519
[Abstract][Full Text]
Cimmino, A., Calin, G. A., Fabbri, M., Iorio, M. V., Ferracin, M., Shimizu, M., Wojcik, S. E., Aqeilan, R. I., Zupo, S., Dono, M., Rassenti, L., Alder, H., Volinia, S., Liu, C.-g., Kipps, T. J., Negrini, M., Croce, C. M.
(2005). miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc. Natl. Acad. Sci. USA
102: 13944-13949
[Abstract][Full Text]
Balakrishnan, K., Wierda, W. G., Keating, M. J., Gandhi, V.
(2005). Mechanisms of Cell Death of Chronic Lymphocytic Leukemia Lymphocytes by RNA-Directed Agent, 8-NH2-Adenosine. Clin. Cancer Res.
11: 6745-6752
[Abstract][Full Text]
Previous
