There is not “a” clonal marker. There are many clonal markers.

First example: any nucleated cell from a woman has one functional X chromosome. The second one does not function. Glucose 6-phosphate dehydrogenase is an X-linked enzyme found in erythrocytes. There are two kinds of G6PD, type A and type B. If the chromosome X is neutralized randomly, you expect to find around 50% type A and 50% type B G6PD. To prove that CML resulted from a pluripotent cell (a precursor of white cells, red cells and platelets), not from a myeloblast (a white cell precursor) type A and type B G6PD were assessed in erythrocytes of many women with CML. Results came out 70% and 30%, or 11% and 89%, showing that the problem was not restricted to leukocytes.

Second example: CML is caused by a gene formed when fragments of chromosomes 9 and 22 break off and trade places . The abl gene from chromosome 9 (genes are represented with three letters, abl is from Abelson murine leukemia) joins to the bcr gene (from breakpoint cluster region protein) on chromosome 22. The resultant chromosome is called chromosome Philadelphia. Different medications were developed to inhibit the abnormal functioning of the bcr-abl gene. One of them is called imatinib (STI571 or Gleevec). If you search Imatinib in wikipedia, you’ll be amazed by the mechanism of action of the medication. Very specific.

You may find that the tumor is clonal by studying cell markers. A good example is cluster of differentiation, CD molecules. CD molecules are surface molecules that act as receptors or ligands, and have an important role in cell signaling. You may detect the percentage of CD molecules by immunophenotyping the cells or the tissue. There are more than 300 CD molecules, so you better know what you are looking for. If I am suspecting that my patient has hairy cell leukemia (a type of leukemia that responds to specific medications) I will ask the laboratory to perform immunophenotyping of the leukocytes in peripheral blood or in the bone marrow. Hairy cell leukemia is characterized by low or no cell-surface expression of CD25 (also called the Interleukin-2 receptor alpha chain).

But clonality is not restricted to tumor markers. Immunoglobulins are cell products, detected in plasma. Electrophoresis allows us to know if they are polyclonal or monoclonal. It is like cars: if they have the same size, the same appearance, they were made by the same factory. If a patient has increased levels of polyclonal immunoglobulins, the immunoglobulins are a response to an infection or to inflammation. Monoclonal immunoglobulins are not reactive (it is impossible to make war only with grenades, isn’t it?). They are the product of cell that lost control and remain producing immunoglobulins even after stimulus cessation (an infection, for instance). Patients with monoclonal immunoglobulins may evolve to a malignant condition or not.

I agree, tumors have distinct clones (just like the fingers of our hands). Depending on the environmental factors (including impact of treatment) a subdominant clone might become predominant

thank you