Hematological malignancies

Thymidine Kinase has been used substantially as biomarker for cell proliferation and disruption in clinical studies of hematological malignancies. It can be used to predict outcome and monitor effectiveness of drug treatment.

Hematological malignancies comprise forms of cancer that begin in the cells of blood-forming tissue, such as the bone marrow, or in the cells of the immune system. Hematological malignancies comprise forms of cancer that begin in the cells of blood-forming tissue, such as the bone marrow, or in the cells of the immune system. Genetic abnormalities such as chromosomal translocations are a common cause of these diseases.

Lymphomas exist as indolent and aggressive forms. Transformation may occur changing the treatment. The most common type is lymphoma (566 000 new cases in 2012), the second most common type is myeloma (488 200 new cases in 2012) and the more uncommon type is leukemia (322 000 new cases in 2012)¹. In 2016 there were 269 000 deaths caused by lymphomas (29 000 Hodgkin’s and 240 000 non-Hodgkin’s lymphomas), 310 000 deaths are caused by leukemia and 98 000 deaths come from myeloma². The number of incidences increases annually due to an aging and growing population as well as a changing population structure. For example, between 2006 and 2016 the incidence of global leukemia increased by 26% and non-Hodgkin’s lymphoma by 45%.

It is common that hematological malignancies are treated using costly and toxic drugs. For example, the recommended treatment for Diffuse Large B-Cell Lymphoma made by the European Society for Medical Oncology (ESMO) consists of 6 to 8 cycles of rituximab + CHOP with intervals of 21 to 28 days in between each cycle. This therapy is costly, and it is critical to monitor the effectiveness of the treatment. Patient monitoring during treatment, post-treatment evaluation and follow-up are made today for at least two years using CT and PET/CET.

AroCell TK 210 ELISA offers a simple and cost-effective assay for monitoring of patients under treatment. Preliminary studies show that AroCell TK 210 ELISA can be used to predict outcome and monitor effectiveness of drug treatment (before, during, and after treatment) in subjects suffering from Diffuse Large B-Cell Lymphoma, the most common non-Hodgkin’s Lymphoma.

 

 

TK1 as a biomarker in hematological malignancies

Thymidine Kinase 1 (TK1) has been used substantially as a cell proliferation and disruption biomarker in subjects suffering from hematological malignancies. TK1 is more practical than other biomarkers such as Ki-67 because it is measurable in both tissues and blood and therefore simplifies serial testing³.

TK1 has been found to be significantly over-expressed in circulating lymphocytes in subjects with aggressive Chronic Lymphocytic Leukemia (CLL) compared with lymphocytes from healthy individuals and subjects with indolent disease4. Tissue TK1 activity in subjects with Non-Hodgkin’s Lymphoma were found to increase in parallel with the occurrence of less well differentiated cells and the clinical Rappaport score4. An increase in intracellular TK1 was associated with a change to more aggressive disease4 and increased cellular TK1 could be a predictive biomarker.

Elevations in serum TK1 are associated with more aggressive hematological malignancies and elevated serum TK1 activities in subjects with chronic lymphocytic leukemia are of increased risk of disease progression5, while subjects with lower serum TK1 values may have improved survival6.

  1. International Agency for Research on Cancer. World Cancer Report (2014). World Health Organization.
    http://publications.iarc.fr/Non-Series-Publications/World-Cancer-Reports/World-Cancer-Report-2014
  1. Alexander M. Castellino. Global burden of hematology malignancies. Hematology Times, (2018).
    https://www.mdedge.com/hematology-oncology/article/184818/leukemia-myelodysplasia-transplantation/global-burden-hematologic?channel=49434
  1. Guan, H. et al. Thymidine Kinase 1 Expression in Atypical Ductal Hyperplasia Significantly Differs from Usual Ductal Hyperplasia and Ductal Carcinoma In-Situ: A Useful Tool in Tumor Therapy Management. Med. Rep. 2(6) (2009), 923-9.
    https://www.ncbi.nlm.nih.gov/pubmed/21475922
  1. Ellims, P.H. et al. Thymidine Kinase Isoenzymes in Human Malignant Lymphoma. Cancer Research41 (1981), 691-695.
    http://cancerres.aacrjournals.org/content/canres/41/2/691.full.pdf
  1. Hallek, M. et al. Elevated Serum Thymidine Kinase Levels Identify a Subgroup at High Risk of Disease Progression in Early, Non-smouldering, Chronic Lymphocytic Leukemia. Blood93(5) (1999), 1732-1737.
    https://www.ncbi.nlm.nih.gov/pubmed/10029603
  1. Gatt, M.E. et al. Thymidine Kinase Levels Correlate with Prognosis in Aggressive Lymphoma and Can Discriminate Patients with a Clinical Suspicion of Indolent to Aggressive Transformation. Anticancer Res. 35(5) (2015), 3019-26.
    https://www.ncbi.nlm.nih.gov/pubmed/25964590