Lymphoma Proteins


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Lymphoma

Lymphoma is the cancer of cells in the lymphatic system such as lymph nodes, spleen, thymus and tissues. Two main types of lymphoma are Hodgkin lymphomas and non-Hodgkin lymphomas that are differentiated via the presence of a single cell type, called the Hodgkin and Reed-Sternberg (HRS) cells present in the Hodgkin lymphoma. There are about 30 different non-Hodgkin lymphomas.

Non-Hodgkin Lymphomas

Non-Hodgkin Lymphoma (NHL), being the most common and the one causing the most number of deaths of all blood cancers, has several subtypes. According to the general subtype, there are B-cell, T-cell and NK-cell neoplasms that are further divided according to their maturation stage as precursor and peripheral neoplasms. Although some types are very rare and their classification is complicated, the classification of non-Hodgkin lymphomas can be summarized (Fig. 1).

Types of non-Hodgkin lymphomas

Fig. 1 Types of non-Hodgkin lymphomas (Harris NL et al. 1994).

Cytogenetics has played a crucial role in providing substantial insight into the genetic mechanisms and aided the classification of lymphoma as well as establishment of some distinct subtypes such as mantle cell lymphoma. Majority of NHLs have a number of clonal and relatively complex chromosome abnormalities that are seen with high frequencies in most of the same lymphoma subtype. However, this genetic alteration lymphoma subtype association is not absolute so other characteristics such as morphology and immunology also have important effect in the classification of the lymphoma. Some of the known genetic rearrangements of some lymphoma subtypes are given in Fig. 2.

Characteristic primary gene aberrations in select B- and T-cell lymphoma subtypes

Fig. 2 Characteristic primary gene aberrations in select B- and T-cell lymphoma subtypes.

The fact that there are so many subtypes and each subtype has its own growth characteristics makes the treatment of NHL complicated. In treatment of lymphoma, there are numerous issues to be taken into account. The clinical behavior of lymphoma, similar to leukemia, strongly depends on the stage of maturation arrest of the tumor lineage. The stage of maturation arrest determines the degree of differentiation, which is directly related to the rate of cell proliferation and cell death. The more differentiated the cancerous cells are the slower the cells proliferate, meaning the life span of the patient is longer if the cancerous cells are differentiated and shorter if they are more primitive. Therefore, accurate diagnosis of the cancer subtype plays an important role in the determination of the required therapy.

Chemotherapy is the leading mode of treatment in blood cancers, often accompanied by radiation therapy or several other drugs that are newly emerging as the research in the area progresses. The radiation therapy used in treatment of cancer also is subjected to many changes with the novel methods of delivery of the ionizing radiation that improves the efficiency of the treatment and decreases the involvement of the nearby healthy tissue. In addition, radioimmunotherapy, a treatment that combines radiation therapy with immunotherapy, is used to treat some types of NHL.

Immunotherapy: Immune cells with capability to recognize and kill cancer cells are produced in the laboratory and given to patients to treat cancer. It is usually used in combination with another therapy such as chemotherapy. It includes (i) monoclonal antibody therapy, where laboratory-produced proteins targeting cancer specific cell surface antigens are infused (ii) cancer vaccines, designed to induce immune response against cancer cells present in the patient after treatment and (iii) donor lymphocyte infusion, where a donor’s lymphocytes are infused to a patient with relapsed cancer after stem cell transplantation.

Gene therapy: Several agents are used to alter the expression of oncogenes and synthesis of corresponding proteins participating in malignancy. Rather than nullifying the effect of the oncoprotein by an external agent, its synthesis could be altered by gene therapy. Instead of protein replacement therapy, for example for a missing tumor-suppressor, a functional gene is delivered to code for the missing protein. As the oncoproteins and missing tumor-suppressors are responsible for development of cancerous features, the prevention of the synthesis of oncoproteins and/or reactivation or reintroduction of the tumor suppressors can cure the cancerous state or cause the death of the cancerous cells. In another approach, gene transfer therapy, the patients’ T-cells are removed, genetically engineered and re-infused after chemotherapy to stop or slow down the remission of the disease.

Stem cell transplantation: when the bone marrow of the patient is impaired due to the blood cancer and/or the treatment, stem cells are transplanted into the patient to restore the function of the bone marrow. The stem cell transplantations are mainly either (i) autologous, where patient’s own stem cells are collected, frozen and then thawed to be returned to the patient after intensive chemotherapy, or (ii) allogeneic, where a matching donor’s stem cells are transplanted into the patient.