• Natural history of monoclonal B-cell lymphocytosis, chronic lymphocytic leukemia, and small lymphocytic lymphoma [ Designated as safety issue: No ]
  
• Characterization of disease stability and progression events [ Designated as safety issue: No ]
  

• Gene expression evaluation of leukemic cells [ Designated as safety issue: No ]
  
• Gene expression correlation with somatic mutations in tumor cells [ Designated as safety issue: No ]
  
• Gene expression profile of lymphocytes [ Designated as safety issue: No ]
  
• Protein expression relationship with gene expression profiles and disease behavior prior to treatment [ Designated as safety issue: No ]
  
• PET scan correlation with gene expression profile in leukemic cells and biologic and prognostic markers of disease [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Study the natural history of monoclonal B-cell lymphocytosis (MBL), chronic lymphocytic leukemia (CLL), and small lymphocytic lymphoma (SLL) in patients prior to the time when their disease requires treatment.
• Characterize clinical, biologic, and molecular events of disease stability and progression in each patient.

Secondary

• Evaluate gene expression by DNA microarray analysis of leukemic cells in blood, bone marrow, and lymph nodes.
• Correlate gene expression analysis with presence or absence of somatic mutations in the tumor cells, such as p53 mutations or deletions, and clinical parameters.
• Evaluate the molecular genetics of lymphocytes from previously untreated MBL/CLL/SLL patients by gene expression profiling on DNA microarrays, chromosomal karyotyping by banding and FISH techniques, comparative genomic hybridization, epigenetic analysis including DNA methylation and histone modifications, or similar techniques.
• Investigate the biology of MBL/CLL/SLL by multicolor flow cytometry analysis and cell sorting (to include single-cell analysis), cell culture, viral transfections, derivation of stable cell lines, and xenograft models.
• Analyze protein expression using various proteomic approaches and presence or absence of protein modifications in relation to gene expression profiles and MBL/CLL/SLL behavior prior to treatment.
• Correlate PET scan with gene expression profile in the leukemic cells and with biologic and prognostic markers of MBL/CLL/SLL.
• Evaluate role of CT scanning in early disease.

OUTLINE: Blood samples are obtained every 3-12 months. Some patients may also undergo apheresis to obtain leukemic cells for in vitro studies related to the biology of monoclonal B-cell lymphocytosis (MBL), chronic lymphocytic leukemia (CLL), and small lymphocytic lymphoma (SLL) or to test and develop new therapies. Bone marrow aspirates and lymph node biopsy material may also be obtained from some patients. Patients undergo PET and/or CT scans periodically.

Samples from patients are analyzed using routine flow cytometric immunophenotyping, FISH cytogenetics, PCR-based assays (for immunoglobulin gene rearrangement), and ZAP-70 immunoperoxidase assays (on bone marrow biopsies, clot sections, and peripheral blood cell blocks). Various methods may be used to analyze gene promoter methylation, histone modifications, somatic mutations in the tumor cells, protein expression, and the presence of protein modifications such as immunoprecipitation, western blotting, flow cytometry analysis and cell sorting, and mass spectrometry and modifications. These analyses are then correlated with the gene expression profiles.

Some cells from patient samples may be kept in culture to study the effects of drugs (including standard therapies or experimental compounds) or the effect of immunotherapeutic approaches. Cultured cells are also used to confirm in vivo observations of gene or protein expression and to establish cell-based models of CLL or SLL. Primary cells may be kept in culture, co-cultured with autologous or allogeneic stroma cells, genetically modified by gene or RNA transfection, or injected into animal models (xenografts). Some cells may be used to establish CLL cell lines.

Patients are followed every 3-12 months until their disease requires treatment.