Title
Metabolic Profiling of Leukemic Cells through Isotope Tracing in Patients with CLL

Description
Metabolic reprogramming has been identified as a hallmark of cancer. Almost a century after Otto Warburg initially discovered increased glycolytic activity in tumor tissue ("Warburg effect"), therapeutic targeting of cancer metabolism has become a field of intense research effort in cancer biology.

A growing appreciation of metabolic heterogeneity and complexity is currently reshaping investigators "simplistic" understanding of metabolic reprogramming in cancer. Discovering metabolic vulnerabilities as new treatment targets for cancer requires systematic dissection of metabolic dependencies, fuel preferences, and underlying mechanisms in the specific physiological context. However, today's data on cancer cell metabolic signatures and heterogeneity in their physiological habitat of the human organism is sparse to non-existent representing a critical knowledge gap in designing effective metabolic therapies. Here, the investigators propose a "top-down" approach studying cancer cell metabolism in patients followed by mechanistic in-depth studies in cell culture and animal models to define metabolic vulnerabilities.

Investigators will develop a metabolic tracing method to quantitatively characterize metabolic signatures and fuel preferences of leukemic lymphocytes in patients with chronic lymphocytic leukemia (CLL). Isotopic metabolic tracers are nutrients that are chemically identical to the native nutrient. Incorporated stable, non-radioactive isotopes allow investigators to follow their metabolic fate by monitoring conversion of tracer nutrients into downstream metabolites using cutting-edge metabolomics analysis. Using this method, investigators propose to test the hypothesis that leukemic lymphocytes show tissue-specific metabolic preferences that differ from non-leukemic lymphocytes and that ex vivo in-plasma labeling represents a useful model for assaying metabolic activity in leukemic cells in a patient-specific manner.

Objective
Develop a metabolic tracing method to quantitatively characterize metabolic signatures and fuel preferences of leukemic lymphocytes in patients with chronic lymphocytic leukemia (CLL) through in vivo and ex vivo stable isotope tracing.

Treatment Active Comparator: Group A: Healthy volunteers
Healthy volunteers are defined as people without a history of cancer

Experimental: Group B subset-1: Treatment naïve CLL(Chronic Lymphocytic Leukemia) patients with low disease burden
Participants with low disease burden CLL (Chronic Lymphocytic Leukemia) defined as confined to Rai stage 0.

Experimental: Group B subset-2: Treatment naïve CLL patients with low disease burden
Participants with low disease burden CLL (Chronic Lymphocytic Leukemia) defined as confined to Rai stage 0.

Experimental: Group C:Treatment naïve CLL patients with high systemic disease burden
Treatment naïve CLL patients with high systemic disease burden

Key Eligibility Inclusion Criteria:
Group A

Adult (18 years of age or older)

No previous history of cancer

Routine history of normal blood counts and vital signs

Documented Informed Consent

Adult (18 years of age or older)

Diagnosis of CLL with low disease burden defined as Rai stage 0 ((Lymphocytosis; no enlargement of the lymph nodes, spleen, or liver; red blood cell and platelet counts are near normal.)

Treatment naïve

Documented Informed Consent

Adult (18 years of age or older)

Diagnosis of CLL with high systemic disease burden defined as infiltration of bone marrow causing cytopenia

Treatment naïve

Able/willing to have bone marrow aspiration

Documented Informed Consent

Prisoners

Psychiatric inpatients or people who are institutionalized

Minor (Less than 18 years of age)

History of diabetes

Cannot be on antihyperglycemic therapy

Carbohydrate restricting diets: Atkins, Vegan, Ketogenic, etc.

Females of child bearing potential

Persons without decision-making capacity

Person who cannot read/write English

Not meeting inclusion criteria defined above

Applicable Disease Sites
Leukemia

Participating Institutions
UW Health University Hospital