The aim of this proposal is to identify immune biomarkers, genetic risk, and the clinical consequences of low count monoclonal B-cell lymphocytosis (LC MBL), a common premalignant condition affecting up to 17% of European adults age\>40. LC MBL is a precursor to chronic lymphocytic leukemia (CLL), characterized by a circulating population of clonal B-cells. It is relatively understudied, despite emerging evidence of clinical consequences such as increased risk for life-threatening infections and lymphoid malignancies. Studies reported that male sex, age, family history of CLL, and CLL-susceptibility genetic loci were associated with LC MBL risk. These findings were reported in European ancestry individuals and have not been generalized to other thnicities. This study will provide this missing knowledge using a unique multi-ethnic Israeli population of Jews and Arabs that have one of the highest and lowest age-standardized incidence rates of CLL in the world, respectively, and characterized with different genetic backgrounds.
Study Type
OBSERVATIONAL
Enrollment
1,500
Assess the relationship between LC MBL and life-threatening infections, hematologic malignancies, and solid tumors among Jews and Arabs in Israel
Blood samples will be screened for MBL using flow cytometry, while data on the various outcomes will be collected from electronic medical records from Clalit Health Services.
Time frame: From enrollment and 15 years of follow up
Assess the relationship between LC MBL and cardiovascular diseases, autoimmune conditions, and Alzheimer among Jews and Arabs in Israel
Blood samples will be screened for MBL using flow cytometry, while data on the various outcomes will be collected from electronic medical records from Clalit Health Services.
Time frame: From enrollment and 15 years of follow up
Identify germline genetic factors that are associated with LC MBL risk among Jews and Arabs in Israel
DNA will be extracted from the blood sample and sequenced.
Time frame: The first 5 years of the study
Evaluate the prevalence of LC MBL by Jews and Arabs and by sex in Israel.
Blood samples will be screened for MBL using flow cytometry, ethnicity and sex will be determined using a demographic questionnaire
Time frame: The first 5 years of the study
Identify immune biomarkers that are associated with LC MBL risk
Blood sample will be screened for MBL using flow cytometry, and immune biomarkers will be screened from plasma samples.
Time frame: The first 5 years of the study
Assess the relationship between LC MBL and other clinical conditions
Other clinical conditions will be determined from electronic medical records from Clalit Health Services
Time frame: From enrollment and 15 years of follow up
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