The question is often asked as to whether there are leukemic stem cells for CLL. The theory goes like this. Most of the cells in a cancer are committed cells without self-renewal capacity. In any tumor there are small numbers of stem cells carrying the basic neoplastic defect that are capable of self-renewal and differentiation. The great bulk of the cells are differentiated cells that have committed themselves to maturation and eventual death. If you transplanted only those, they would eventually die out because they do not have the capacity for self-renewal. It is suggested that such cells are the ones that are killed by conventional therapy, while the true stem cells are resistant to treatment. This explains the phenomenon of remission and relapse. The great bulk of cells of the tumor are not stem cells so that when they respond to treatment the patient appears to be in complete remission. However, lurking somewhere in the body are the stem cells that are resistant to the treatment, and when the coast is clear they will start dividing and replenish all the cells that have been killed so that the disease relapses.
This scenario certainly appears to be the case for many solid tumors like colon cancer and pancreatic cancer, and is also the case for myeloid leukemias, both acute and chronic. Is it also the case for lymphoid tumors, and especially for CLL?
I submit that it cannot be so. The stem cells of lymphocytes are pluripotent blasts found in the bone marrow, that can commit to either myeloid or lymphoid tumors. That is why in chronic myeloid leukemia, transformation can be to either acute myeloid leukemia or acute lymphoid leukemia. However, lymphoid tumors mostly arise from lymphocytes that have already committed themselves by rearranging their immunoglobulin genes (in the case of B cells tumors) or their T cell receptor genes (in the case of T cell tumors). This is a step that can't be gone back on. You can certainly conceive of a stem cell origin for a lymphoid tumor, but there is no reason that all the cells in such a tumor would have the same Ig rearrangement in every cell as happens in CLL, myeloma and mantle cell lymphoma, and while where there is some variation in follicular lymphoma, it is usually possible to construct a 'family tree' of the variations demonstrating an origin in a single cell.
If relapse in CLL was fed by a self-renewing stem cell from a lineage arising before Ig rearrangement the relapsing tumor would have a different rearrangement.
In fact lymphocytes have a circular lifestyle. The apparently small mature lymphocytes of CLL can turn back into blasts capable of division before resuming their 'mature' appearance again. there is no need for a stem cell to answer the relapse/remission conundrum. There may certainly be cells that lack Cd20 and are thus immune to rituximab, but they are not stem cells in the conventional way.