Acute promyelocytic leukemia

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Acute promyelocytic leukemia

Acute promyelocytic leukemia is a subtype of acute myelogenous leukemia (AML), a cancer

Cancer

Cancer is a class of diseases in which a group of cell display uncontrolled growth , invasion , and sometimes metastasis . These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize....
of the blood

Blood

Blood is a specialized bodily fluid that delivers necessary substances to the body's Cell s ? such as nutrients and oxygen ? and transports waste products away from those same cells....
and bone marrow

Bone marrow

Bone marrow is the flexible biological tissue found in the hollow interior of bones. In adults, marrow in large bones produces new blood cells....
. It is also known as acute progranulocytic leukemia; APL; AML with t(15;17)(q22;q12), PML-RARA and variants; FAB subtype M3 and M3 variant.

In APL, there is an abnormal accumulation of immature granulocytes called promyelocytes

Promyelocyte

A promyelocyte is a granulocyte precursor, developing from the myeloblast and developing into the myelocyte....
. The disease is characterized by a chromosomal translocation

Chromosomal translocation

In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A fusion gene may be created when the translocation joins two otherwise separated genes, an event which is common in cancer....
involving the retinoic acid receptor

Retinoic acid receptor

The retinoic acid receptor is a type of nuclear receptor which is activated by both retinoic acid and retinoic acid. There are three retinoic acid receptors , retinoic acid receptor alpha, retinoic acid receptor beta, and retinoic acid receptor gamma encoded by the , , genes respectively....
alpha (RARa or RARA) gene and is unique from other forms of AML in its responsiveness to all trans retinoic acid

Atra

Atra or ATRA can refer to:*Stachybotrys chartarum*All-trans retinoic acid*American Tort Reform Association*the location of an Arabic fortress west of the Tigris...
(ATRA) therapy.

Acute promyelocytic leukemia was first characterized in 1957.

s and symptoms of acute promyelocytic leukemia are similar to other forms of AML.

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Encyclopedia

Acute promyelocytic leukemia is a subtype of acute myelogenous leukemia (AML), a cancer

Cancer

Blood

Bone marrow

Promyelocyte

A promyelocyte is a granulocyte precursor, developing from the myeloblast and developing into the myelocyte....
. The disease is characterized by a chromosomal translocation

Chromosomal translocation

Retinoic acid receptor

Atra

Signs and symptoms

Signs and symptoms of acute promyelocytic leukemia are similar to other forms of AML. Symptoms include fever

Fever

Fever is a frequent medical sign that describes an increase in internal body temperature to levels above normal. Fever is most accurately characterized as a temporary elevation in the body's thermoregulatory set-point, usually by about 1?2 ?C ....
, fatigue

Fatigue (physical)

Fatigue is a weariness caused by exertion. It can describe a range of afflictions, varying from a general state of wikt:lethargy to a specific work-induced burning sensation within one's muscles....
, weight loss

Weight loss

Weight loss, in the context of medicine or health or physical fitness, is a reduction of the total body weight, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue....
or loss of appetite, shortness of breath with exertion, anemia

Anemia

Anemia or an?mia/anaemia is defined as a qualitative or quantitative deficiency of hemoglobin, a protein found inside red blood cells ....
, easy bruising or bleeding, petechiae (flat, pin-head sized spots under the skin caused by bleeding), bone pain and joint pain and persistent or frequent infections.

The accumulation of promyelocytes in the bone marrow results in a reduction in the production of normal red blood cell

Red blood cell

Red blood cells are the most common type of blood cell and the vertebrate body's principal means of delivering oxygen to the body tissues via the blood....
s and platelet

Platelet

Platelets, or Thrombocyte, are small, irregularly shaped anuclear cells, 2-4?m in diameter, which are derived from fragmentation of precursor megakaryocytes....
s resulting in anemia

Anemia

Anemia or an?mia/anaemia is defined as a qualitative or quantitative deficiency of hemoglobin, a protein found inside red blood cells ....
and thrombocytopenia

Thrombocytopenia

Thrombocytopenia is the presence of relatively few platelets in blood.Generally speaking, in humans, a normal platelet count ranges from 150,000 and 450,000 per mm3....
. Either leukopenia

Leukopenia

Leukopenia is a decrease in the number of circulating white blood cells in the blood. As the principal function of white cells is to combat infection, a decrease in the number of these cells can place patients at increased risk for infection....
(low white cell count) or leukocytosis

Leukocytosis

Leukocytosis is a raised white blood cell count above the normal range. This increase in leukocytes is usually accompanied by a "left shift" in the ratio of immature to mature neutrophils....
(high white cell count) may be observed in the peripheral blood.

Symptoms include:

Fatigue, weakness, shortness of breath (from anemia)
Easy bruising and bleeding (from thrombocytopenia and coagulopathy
Coagulopathy

Coagulopathy is a medical term for a defect in the body's mechanism for blood clotting....
)
Fever and infection (from lack of normal white blood cells)

In addition, acute promyelocytic leukemia is frequently associated with bleeding caused by disseminated intravascular coagulation

Disseminated intravascular coagulation

Disseminated intravascular coagulation , also known as consumptive coagulopathy, is a pathological activation of coagulation mechanisms that happens in response to a variety of diseases....
(DIC).

Epidemiology

Acute promyelocytic leukemia represents 5-8% of AML in adults. The median age is approximately 40 years, which is considerably younger than the other subtypes of AML (70 years). The incidence is increased in patients originated in Latin American countries.

Pathogenesis

Acute promyelocytic leukemia is characterized by chromosomal translocation involving the retinoic acid receptor-alpha gene on chromosome 17 (RARa). In 95% of cases of APL, retinoic acid receptor-alpha (RARa) gene on chromosome 17 is involved in a reciprocal translocation with the promyelocytic leukemia gene (PML) on chromosome 15, a translocation denoted as t(15;17)(q22;q12).

Four other gene rearrangements have been described in APL fusing RARa to promyelocytic leukemia zinc finger (PLZF), nucleophosmin (NPM), nuclear matrix associated (NUMA), or signal transducer and activator of transcription 5b (STAT5B) genes.

The resultant fusion proteins disrupt the function of RARa which blocks the normal maturation of granulocytes. Although the chromosomal translocation involving RARa is believed to be the initiating event, additional mutations are required for the development of leukemia.

Diagnosis

Acute promyelocytic leukemia can be distinguished from other types of AML based on morphologic examination of a bone marrow biopsy

Bone marrow biopsy

Bone marrow examination refers to the pathology analysis of samples of bone marrow obtained by bone marrow biopsy and bone marrow aspiration....
or aspirate. Definitive diagnosis requires testing for the RARa fusion gene. This may be done by polymerase chain reaction

Polymerase chain reaction

The polymerase chain reaction is a technique widely used in molecular biology. It derives its name from one of its key components, a DNA polymerase used to amplify a piece of DNA by in vitro enzyme DNA replication....
(PCR), fluorescent in situ hybridization

Fluorescent in situ hybridization

FISH is a cytogenetics technique that can be used to detect and localize the presence or absence of specific DNA DNA sequence on chromosomes. It uses hybridization probe that bind to only those parts of the chromosome with which they show a high degree of sequence similarity....
(FISH), or conventional cytogenetics

Cytogenetics

Cytogenetics is a branch of genetics that is concerned with the study of the structure and function of the cell, especially the chromosomes. It includes routine analysis of G banding chromosomes, other cytogenetic banding techniques, as well as molecular cytogenetics such as fluorescent in situ hybridization and comparative genomic hybridiz...
of peripheral blood or bone marrow.

Monitoring for relapse using PCR tests for RARa allows early re-treatment which is successful in many instances.

Treatment

APL is unique among the leukemias distinguished by its sensitivity to all-trans retinoic acid (ATRA), a derivative of vitamin A

Vitamin A

Vitamin A, a bi-polar molecule formed with bi-polar covalent bonds between carbon and hydrogen, is linked to a family of similarly shaped molecules, the retinoids, which complete the remainder of the vitamin sequence....
. Treatment with ATRA causes differentiation of the immature leukemic promyelocytes into mature granulocytes. ATRA is typically combined with anthracycline

Anthracycline

Anthracyclines are a class of drugs used in chemotherapy derived from Streptomyces bacteria .These compounds are used to treat a wide range of cancers, including leukemias, lymphomas, and breast cancer, uterine cancer, ovarian cancer, and lung cancers....
based chemotherapy resulting in a clinical remission in approximately 90% of patients.

ATRA therapy is associated with the unique side effect of retinoic acid syndrome

Retinoic acid syndrome

Retinoic acid syndrome is a potentially life threatening complication seen in patients with acute promyelocytic leukemia who are treated with Tretinoin ....
. This is associated with the development of dyspnea, fever, weight gain, peripheral edema and is treated with dexamethasone

Dexamethasone

Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid hormones. It acts as an anti-inflammatory and immunosuppressive drug....
. The etiology of retinoic acid syndrome has been attributed to capillary leak syndrome from cytokine release from the differentiating promyelocytes.

Allogeneic stem cell transplant

Bone marrow transplant

Hematopoietic stem cell transplantation is the transplantation of Pluripotential hemopoietic stem cell derived from the bone marrow or blood. Stem cell transplantation is a medical procedure in the fields of hematology and oncology, most often performed for people with diseases of the blood, bone marrow, or certain types of cancer....
is a treatment option in APL. Remission with use of arsenic trioxide

Arsenic trioxide

Arsenic trioxide is the most important commercial compound of arsenic, and the main starting material for arsenic chemistry. It is the highly toxic byproduct of certain kinds of ore processing, for example gold mining....
has been reported.

External links

ACUTE MYELOID LEUKEMIA IN ADULTS
at University of Virginia
University of Virginia

The University of Virginia is a public university research university located in Charlottesville, Virginia, founded by Thomas Jefferson. Conceived by 1800 and established in 1819, it is the only university in the United States to be designated a World Heritage Site by UNESCO, an honor it shares with nearby Monticello....
at Nagoya University
Nagoya University

, abbreviated to , is a Japanese national university headquartered in Chikusa-ku, Nagoya, and is considered as one of the most prestigious universities in Japan....