Lymphoproliferative disorders
Encyclopedia
Lymphoproliferative disorders (LPDs) refer to several conditions in which lymphocytes are produced in excessive quantities. They typically occur in patients who have compromised immune system
s. They are sometimes equated with "immunoproliferative disorders
", but technically Lymphoproliferative disorders are a subset of immunoproliferative disorders, along with hypergammaglobulinemia
and paraproteinemias.
s into a monoclonal
lymphocytosis
. The two major types of lymphocytes are B cells and T cells, which are derived from pluripotent hematopoetic stem cells in the bone marrow. Individuals who have some sort of immunodysfuction are susceptible to developing a lymphoproliferative disorder because when any of the numerous control points of the immune system become dysfunctional, immunodeficiency
or deregulation of lymphocytes is more likely to occur. There are several inherited gene gene mutations
that have been identified to cause lymphoproliferative disorders, however there are also acquired and iatrogenic causes.
that has been found to be associated with a T cell
and NK cell lymphoproliferative disorder.
. Which is located on the long arm of chromosome 10 at position 24.1, denoted 10q24.1. This gene is member 6 of the TNF-receptor superfamily (TNFRSF6). The Fas receptor contains a death domain and has been shown to play a central role in the physiological regulation of programmed cell death. Normally, stimulation of recently activated T cells by antigen leads to coexpression of Fas and Fas receptor on the T cell surface. The engagement of Fas by Fas receptor results in apoptosis
of the cell and is important for eliminating T cells that are repeatedly stimulated by antigens. As a result of the mutation in the Fas receptor gene, there is no recognition of Fas by Fas receptor
, leading to a primitive population of T cells that proliferates in an uncontrolled manner.
infections, and are predisposed to develop a lymphoproliferative disorder or lymphoma.
Children with common variable immune deficiency (CVID) are also at a higher risk of developing a lymphoproliferative disorder.
Some disorders that predispose a person to lymphoproliferative disorders are severe combined immuno deficiency (SCID), Chédiak-Higashi syndrome
, Wiskott-Aldrich syndrome (an X-linked recessive disorder) and Ataxia telangiectasia
.
Interestingly, even though Ataxia telangiectasia is an autosomal recessive disorder, people who are heterozygotes for this still have an increased risk of developing a lymphoproliferative disorder.
infection because it is highly associated with acquired immunodeficiency, which often leads to lymphoproliferative disorders.
therapies. In most reported cases, these cause B cell lymphoproliferative disorders, however some T cell variations have been described. The T cell variations are usually caused by the prolonged use of T cell suppressant drugs, such as sirolimus
, tacrolimus
or cyclosporine A.
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
s. They are sometimes equated with "immunoproliferative disorders
Immunoproliferative disorders
Immunoproliferative disorders are disorders of the immune system that are characterized by the abnormal proliferation of the primary cells of the immune system, which includes B cells, T cells and Natural killer cells, or by the excessive production of immunoglobulins Immunoproliferative...
", but technically Lymphoproliferative disorders are a subset of immunoproliferative disorders, along with hypergammaglobulinemia
Hypergammaglobulinemia
Hypergammaglobulinemia is a medical condition with elevated levels of gamma globulin.It is a type of immunoproliferative disorder.- Types :...
and paraproteinemias.
Examples of LPDs
- follicular lymphomaFollicular lymphomaFollicular lymphoma is the most common of the indolent non-Hodgkin's lymphomas, and the second most common form of non-Hodgkin's lymphomas overall. It is defined as a lymphoma of follicle center B-cells , which has at least a partially follicular pattern...
- chronic lymphocytic leukemiaChronic lymphocytic leukemiaB-cell chronic lymphocytic leukemia , also known as chronic lymphoid leukemia , is the most common type of leukemia. Leukemias are cancers of the white blood cells . CLL affects B cell lymphocytes. B cells originate in the bone marrow, develop in the lymph nodes, and normally fight infection by...
- acute lymphoblastic leukemiaAcute lymphoblastic leukemiaAcute lymphoblastic leukemia is a form of leukemia, or cancer of the white blood cells characterized by excess lymphoblasts.Malignant, immature white blood cells continuously multiply and are overproduced in the bone marrow. ALL causes damage and death by crowding out normal cells in the bone...
- hairy cell leukemiaHairy cell leukemiaHairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. It is usually classified as a sub-type of chronic lymphoid leukemia...
- lymphomaLymphomaLymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
s - multiple myelomaMultiple myelomaMultiple myeloma , also known as plasma cell myeloma or Kahler's disease , is a cancer of plasma cells, a type of white blood cell normally responsible for the production of antibodies...
- Waldenstrom's macroglobulinemia
- Wiskott-Aldrich syndromeWiskott-Aldrich syndromeWiskott–Aldrich syndrome is a rare X-linked recessive disease characterized by eczema, thrombocytopenia , immune deficiency, and bloody diarrhea . It is also sometimes called the eczema-thrombocytopenia-immunodeficiency syndrome in keeping with Aldrich's original description in 1954...
- post-transplant lymphoproliferative disorderPost-transplant lymphoproliferative disorderPost-transplant lymphoproliferative disorder is the name given to a B-cell proliferation due to therapeutic immunosupression after organ transplantation. These patients may develop infectious mononucleosis-like lesions or polyclonal polymorphic B-cell hyperplasia...
- Autoimmune lymphoproliferative syndrome (ALPS)
- "Lymphoid interstitial pneumonia"
Types
Lymphoproliferative disorders are a set of disorders characterized by the abnormal proliferation of lymphocyteLymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s into a monoclonal
Monoclonal
Monoclonal cells are defined as a group of cells produced from a single ancestral cell by repeated cellular replication. Thus they can be said to form a single "clone". The process of replication can occur in vivo, or may be stimulated in vitro for laboratory manipulations...
lymphocytosis
Lymphocytosis
Lymphocytosis is an increase in the number or proportion of lymphocytes in the blood, usually detected when a complete blood count is routinely obtained. Lymphocytes normally represent 20 to 40% of circulating white blood cells...
. The two major types of lymphocytes are B cells and T cells, which are derived from pluripotent hematopoetic stem cells in the bone marrow. Individuals who have some sort of immunodysfuction are susceptible to developing a lymphoproliferative disorder because when any of the numerous control points of the immune system become dysfunctional, immunodeficiency
Immunodeficiency
Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired but some people are born with defects in their immune system,...
or deregulation of lymphocytes is more likely to occur. There are several inherited gene gene mutations
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
that have been identified to cause lymphoproliferative disorders, however there are also acquired and iatrogenic causes.
X-linked Lymphoproliferative disorder
There is a mutation on the X chromosomeX chromosome
The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...
that has been found to be associated with a T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
and NK cell lymphoproliferative disorder.
Autosomal lymphoproliferative disorder
Some children with autoimmune lymphoproliferative disorders are heterozygous for a mutation in the gene that codes for the Fas receptorFas receptor
The FAS receptor also known as apoptosis antigen 1 , cluster of differentiation 95 or tumor necrosis factor receptor superfamily member 6 is a protein that in humans is encoded by the TNFRSF6 gene....
. Which is located on the long arm of chromosome 10 at position 24.1, denoted 10q24.1. This gene is member 6 of the TNF-receptor superfamily (TNFRSF6). The Fas receptor contains a death domain and has been shown to play a central role in the physiological regulation of programmed cell death. Normally, stimulation of recently activated T cells by antigen leads to coexpression of Fas and Fas receptor on the T cell surface. The engagement of Fas by Fas receptor results in apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
of the cell and is important for eliminating T cells that are repeatedly stimulated by antigens. As a result of the mutation in the Fas receptor gene, there is no recognition of Fas by Fas receptor
Fas receptor
The FAS receptor also known as apoptosis antigen 1 , cluster of differentiation 95 or tumor necrosis factor receptor superfamily member 6 is a protein that in humans is encoded by the TNFRSF6 gene....
, leading to a primitive population of T cells that proliferates in an uncontrolled manner.
Other inherited causes
Boys with X-linked immunodeficiency syndrome are at a higher risk of mortality associated with Epstein-Barr VirusEpstein-Barr virus
The Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...
infections, and are predisposed to develop a lymphoproliferative disorder or lymphoma.
Children with common variable immune deficiency (CVID) are also at a higher risk of developing a lymphoproliferative disorder.
Some disorders that predispose a person to lymphoproliferative disorders are severe combined immuno deficiency (SCID), Chédiak-Higashi syndrome
Chédiak-Higashi syndrome
Chédiak–Higashi syndrome is a rare autosomal recessive disorder that arises from a microtubule polymerization defect which leads to a decrease in phagocytosis. The decrease in phagocytosis results in recurrent pyogenic infections, partial albinism and peripheral neuropathy...
, Wiskott-Aldrich syndrome (an X-linked recessive disorder) and Ataxia telangiectasia
Ataxia telangiectasia
Ataxia telangiectasia is a rare, neurodegenerative, inherited disease that affects many parts of the body and causes severe disability. Ataxia refers to poor coordination and telangiectasia to small dilated blood vessels, both of which are hallmarks of the disease...
.
Interestingly, even though Ataxia telangiectasia is an autosomal recessive disorder, people who are heterozygotes for this still have an increased risk of developing a lymphoproliferative disorder.
Acquired causes
Viral infection is a very common cause of lymphoproliferative disorders. The most common is congenital HIVHIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
infection because it is highly associated with acquired immunodeficiency, which often leads to lymphoproliferative disorders.
Iatrogenic causes
There are many lymphoproliferative disorders that are associated with organ transplantation and immunosuppressantImmunosuppressant
An immunosuppressant is any substance that performs immunosuppression of the immune system. They may be either exogenous, as immunosuppressive drugs, or endogenous, as ,e. g., testosterone...
therapies. In most reported cases, these cause B cell lymphoproliferative disorders, however some T cell variations have been described. The T cell variations are usually caused by the prolonged use of T cell suppressant drugs, such as sirolimus
Sirolimus
Sirolimus , also known as rapamycin, is an immunosuppressant drug used to prevent rejection in organ transplantation; it is especially useful in kidney transplants. A macrolide, sirolimus was first discovered as a product of the bacterium Streptomyces hygroscopicus in a soil sample from Easter...
, tacrolimus
Tacrolimus
Tacrolimus is an immunosuppressive drug that is mainly used after allogeneic organ transplant to reduce the activity of the patient's immune system and so lower the risk of organ rejection...
or cyclosporine A.
See also
- Evans syndromeEvans syndromeEvans syndrome is an autoimmune disease in which an individual's antibodies attack their own red blood cells and platelets. Both of these events may occur simultaneously or one follow on from the other....
- Leukaemia
- LymphomaLymphomaLymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
- LymphocytosisLymphocytosisLymphocytosis is an increase in the number or proportion of lymphocytes in the blood, usually detected when a complete blood count is routinely obtained. Lymphocytes normally represent 20 to 40% of circulating white blood cells...
- Myeloma
- Myeloproliferative diseaseMyeloproliferative diseaseThe myeloproliferative diseases are a group of diseases of the bone marrow in which excess cells are produced. They are related to, and may evolve into, myelodysplastic syndrome and acute myeloid leukemia, although the myeloproliferative diseases on the whole have a much better prognosis than...