Adult T-cell leukemia
Encyclopedia
Adult T-cell leukemia/lymphoma (ATL) is a rare cancer
of the immune system's own T-cells.
Human T cell leukemia/lymphotropic virus type 1 (HTLV-1) is believed to be the cause of it, in addition to several other diseases.
. Circulating lymphocyte
s with an irregular nuclear contour (leukemic cells) are frequently seen. Several lines of evidence suggest that HTLV-1 causes ATL. This evidence includes the frequent isolation of HTLV-1 from patients with this disease and the detection of HTLV-1 proviral genome
in ATL leukemic cells. ATL is frequently accompanied by visceral involvement, hypercalcemia, lytic bone lesions, and skin lesions. Most patients die within one year of diagnosis.
Infection with HTLV-1, like infection with other retroviruses, probably occurs for life and can be inferred when antibody
against HTLV-1 is detected in the serum
.
or sharing of contaminated needles.
and the CHOP
regimen. Pralatrexate has also been investigated. Most therapy is directed towards the cancer rather than the virus itself.
Recently, it has been reported that the traditional glucocorticoid-based chemotherapy toward ATL are largely mediated by thioredoxin binding protein-2 (TBP-2/TXNIP/VDUP1), suggesting the potential use of a TBP-2 inducer as a novel therapeutic target.
appears to be rare. Although little serologic data exist, prevalence of infection is thought to be highest among blacks living in the Southeast. A prevalence rate of 30% has been found among black intravenous drug abusers in New Jersey
, and a rate of 49% has been found in a similar group in New Orleans. It is possible that prevalence of infection is increasing in this risk group. Studies of HTLV-1 antibody indicate that the virus is endemic in southern Japan
, in the Caribbean
, South America
, and in Africa
.
ATL is relatively uncommon among those infected with HTLV-1. The overall incidence of ATL is estimated at about 1 per 1,500 adult HTLV-1 carriers per year. Those cases that have been reported have occurred mostly among persons from the Caribbean or blacks from the Southeast (National Institutes of Health, unpublished data). There appears to be a long latent period between HTLV-1 infection and the start of ATL.
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
of the immune system's own T-cells.
Human T cell leukemia/lymphotropic virus type 1 (HTLV-1) is believed to be the cause of it, in addition to several other diseases.
Signs and symptoms
ATL is usually a highly aggressive non-Hodgkin's lymphoma with no characteristic histologic appearance except for a diffuse pattern and a mature T-cell phenotypePhenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
. Circulating lymphocyte
Lymphocyte
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 with an irregular nuclear contour (leukemic cells) are frequently seen. Several lines of evidence suggest that HTLV-1 causes ATL. This evidence includes the frequent isolation of HTLV-1 from patients with this disease and the detection of HTLV-1 proviral genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
in ATL leukemic cells. ATL is frequently accompanied by visceral involvement, hypercalcemia, lytic bone lesions, and skin lesions. Most patients die within one year of diagnosis.
Infection with HTLV-1, like infection with other retroviruses, probably occurs for life and can be inferred when antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
against HTLV-1 is detected in the serum
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
.
Transmission
Transmission of HTLV-1 is believed to occur from mother to child; by sexual contact; and through exposure to contaminated blood, either through blood transfusionBlood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
or sharing of contaminated needles.
Treatment
Treatment options that have been tried include zidovudineZidovudine
Zidovudine or azidothymidine is a nucleoside analog reverse-transcriptase inhibitor , a type of antiretroviral drug used for the treatment of HIV/AIDS. It is an analog of thymidine....
and the CHOP
CHOP
CHOP is the acronym for a chemotherapy regimen used in the treatment of non-Hodgkin lymphoma. CHOP consists of:* Cyclophosphamide, an alkylating agent which damages DNA by binding to it and causing cross-links...
regimen. Pralatrexate has also been investigated. Most therapy is directed towards the cancer rather than the virus itself.
Recently, it has been reported that the traditional glucocorticoid-based chemotherapy toward ATL are largely mediated by thioredoxin binding protein-2 (TBP-2/TXNIP/VDUP1), suggesting the potential use of a TBP-2 inducer as a novel therapeutic target.
Epidemiology
HTLV-1 infection in the United StatesUnited States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
appears to be rare. Although little serologic data exist, prevalence of infection is thought to be highest among blacks living in the Southeast. A prevalence rate of 30% has been found among black intravenous drug abusers in New Jersey
New Jersey
New Jersey is a state in the Northeastern and Middle Atlantic regions of the United States. , its population was 8,791,894. It is bordered on the north and east by the state of New York, on the southeast and south by the Atlantic Ocean, on the west by Pennsylvania and on the southwest by Delaware...
, and a rate of 49% has been found in a similar group in New Orleans. It is possible that prevalence of infection is increasing in this risk group. Studies of HTLV-1 antibody indicate that the virus is endemic in southern Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
, in the Caribbean
Caribbean
The Caribbean is a crescent-shaped group of islands more than 2,000 miles long separating the Gulf of Mexico and the Caribbean Sea, to the west and south, from the Atlantic Ocean, to the east and north...
, South America
South America
South America is a continent situated in the Western Hemisphere, mostly in the Southern Hemisphere, with a relatively small portion in the Northern Hemisphere. The continent is also considered a subcontinent of the Americas. It is bordered on the west by the Pacific Ocean and on the north and east...
, and in Africa
Africa
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
.
ATL is relatively uncommon among those infected with HTLV-1. The overall incidence of ATL is estimated at about 1 per 1,500 adult HTLV-1 carriers per year. Those cases that have been reported have occurred mostly among persons from the Caribbean or blacks from the Southeast (National Institutes of Health, unpublished data). There appears to be a long latent period between HTLV-1 infection and the start of ATL.
Research
Novel approaches to the treatment of PTCL in the relapsed or refractory setting are under investigation. Pralatrexate is one compound currently under investigations for the treatment of PTCL.In pregnancy
Leukemia is rarely associated with pregnancy, affecting only about 1 in 10,000 pregnant women. How it is handled depends primarily on the type of leukemia. Acute leukemias normally require prompt, aggressive treatment, despite significant risks of pregnancy loss and birth defects, especially if chemotherapy is given during the developmentally sensitive first trimester.External links
- Genoveffa Franchini's NCI page: Human Retroviral Diseases: Pathogenesis and Prevention
- International Retrovirology Association