ION Profile in Patient with Chronic Lymphocytic Leukemia (CLL)

Summary

Very high quinolinate & picolinate signal strong activation of the kynurenine pathway, secondary to cell-mediated immune activation. Over-stimulation of the kynurenine pathway can diminish tryptophan levels to the point that T-cell responses are inhibited, leading to poor prognosis in leukemia patients.

History

A 63-year-old female with CLL was recommended to undertake an ION^TM Profile by her referring doctor as part of a work-up for a comprehensive nutritional treatment program. Other relevant pathology included: raised liver enzymes; high anion gap; low platelet white cells, neutrophils and lymphocyte counts; all consistent with active CLL. Symptom wise, the main complaints consisted of: fatigue; poor concentration, memory and comprehension; joint pain; weakness; leg cramps; dry skin; poor night vision; itchy eyes and swollen eye lids; blurred vision; bloating & belching; shortness of breath and frequent urination.

Age

63

Gender

Female

Description of Results

Quinolinate & Picolinate 

Quinolinate and picolinate are the two highest markers on the patient’s ION Profile. Quinolinate is over 5 times the upper 95% reference interval whereas picolinate is over 3 times the upper 95% reference interval.   

Indoleamine 2,3-dioxygenase (IDO) is the key inducer of tryptophan degradation in the kynurenine pathway. Indeed, IDO is the ‘rate-limiting’ enzyme for the kynurenine pathway and is expressed in a variety of tissues. It is highly induced by bacterial and viral infection, which is mediated mainly by IFN-g. This results in increased tryptophan degradation along the kynurenine pathway. The tryptophan degradation induced by IDO during infection plays a role in the defense mechanism against the infectious pathogens. It results in tryptophan depletion that in turn suppresses the growth of many types of viruses, parasites and infectious bacteria.

Escape of Tumor Cells From Immune Surveillance By IDO Expression

Immune escape is a crucial property of cancer progression. Researchers have established that most human malignant tumor cells express IDO. 

Neurotoxic Quinolinate

Some of the intermediate metabolites of the kynurenine pathway are neuroactive. Of these, much attention has been focused on quinolinate. When injected intracerebrally, quinolinate has been shown to cause neural death. 

Quinolinate & Oxidative Stress  

Given that induction of IDO is an inflammatory response of the cell-mediated immune system, elevation of kynurenine pathway intermediates is often accompanied by oxidative stress.

Botanical Treatment of IDO

In light of the newly discovered role IDO plays in the regulation of the body’s inflammatory response, a number of studies have explored the efficacy of certain noted anti-inflammatory botanical extracts or actives. Active components of turmeric, green tea, garlic, St. John's Wort, rosemary, cinnamon, chocolate and even beer have been shown to inhibit the expression of IDO in different capacities.

Ammonia Overload & Asparaginase

Markers from the 20 Plasma-Amino Acid Analysis and Oranix Profile suggest the patient has a derangement in their ammonia meabolism and detoxification. Asparaginase is often given as a chemotherapeurtic agent to patients with leukemia. It takes advantage of the fact that all leukemic cells are unable to synthesize the nonessential amino acid asparagine, and therefore have to depend on circulating asparagine for supply. Asparaginase, however, catalyses the conversion of L-asparagine to aspartic acid and ammonia. This deprives the leukemic cell of circulating asparagine. It is not known whether the patient had used or is using asparaginase as a chemotherapeutic agent.

Calcium D-Glucarate and Urinary Glucarate

The very high urinary glucarate exhibited by this patient is normally a sign of liver induction due to prescription drugs/medication, which undergo extensive first-pass hepatic metabolism.

Potassium & Magnesium

ION^TM Profile are low levels of potassium and magnesium. Low potassium levels have been documented in numerous studies of leukaemia patients including patients with CLL. It is thought this may be due to kidney dysfunction, which is a common feature in leukemia patients. The referring clinician may want to prescribe potassium supplements to offset the deficiency. The patient reports to be taking magnesium, however, her levels are still suboptimal. The referring clinician might suggest the patient increase her daily dose.  

Another abnormality on this patient’s 

In most cases of infection, the induction of IDO is limited to the tissues infected with the pathogens.The patient reports mild depression, anxiety and diarrhea, which indicates she may be in the early stages of tryptophan depletion. If strong induction of IDO is allowed to continue, we might expect these symptoms to worsen. Many other essential amino acids are low, which suggests the patient’s protein intake and absorption is compromised. Muscle tissue catabolism secondary to leukemia may also be a factor as low threonine levels have been linked to heightened catabolism.

Functional CoQ10 Deficiency

Elevation of succinate and hydroxymethyglutarate are specific indicators of a functional CoQ10 deficiency. A statin drug by the name of Lovastatin is commonly used to treat acute myeloid leukaemia, however, it is not know whether such medication has been previously used by this patient. Excluding this, the deficiency may simply be due to oxidative stress secondary to the CLL.

Functional Carnitine Deficiency

Studies in children and adolescents with leukemia have shown levels of carnitine to be depressed in the early stages of disease. Thus, supplementation with carnitine may be warranted.

Recommendations

High levels of quinolinate and picolinate on this patient’s test signify that there is strong induction of IDO by IFN-g. Quinolinate levels in cancer and leukemia patients can serve as a useful prognostic tool, with high quinolinate levels correlated with poor treatment prognosis. Pharmceutical, nutritional or botanical adjunctive treatments aimed at suppressing IDO activity should be a major consideration for the patient. Ongoing monitoring of the kynurenine pathway via follow up OrganixTM Profile testing will be important to monitor treatment efficacy.

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