cchoi1022/wikitext-103-v1 · Datasets at Hugging Face

text stringlengths 0 6.86k

most rails are secretive wetland birds that have made little cultural impression but as a formerly common farmland bird with a loud nocturnal call that sometimes led to disturbed sleep for rural dwellers the corn crake has acquired a variety of folk names and some commemoration in literature

= = = names = = =

the favoured name for this species among naturalists has changed over the years with <unk> and variants of corncrake being preferred at various times crake gallinule also had a period of popularity between 1768 and 1813 the originally older scots <unk> was popularised by thomas bewick who used this term in his 1797 a history of british birds other scots names include corn <unk> and <unk> the latter term like king of the quail grass quail the french roi de caille and the german <unk> refer to the association with the small gamebird another name <unk> has been variously interpreted as onomatopoeic or derived from the old norse ager @@ <unk> meaning cock of the field variants include drake drake hen and gorse drake

= = = in literature = = =

corn crakes are the subject of three stanzas of the seventeenth century poet andrew marvell 's upon appleton house written in 1651 about the north yorkshire country estate of thomas fairfax the narrator depicts the scene of a mower cutting the grass before his whistling <unk> unknowingly carves the rail the farmhand draws out the scythe all bloody from its breast and does the stroke detest it continues with a stanza that demonstrates the problematic nature of the corn crake 's nesting habits
john clare the nineteenth @@ century english poet based in northamptonshire wrote the landrail a semi @@ comic piece which is primarily about the difficulty of seeing corn crakes as opposed to hearing them in the fourth verse he exclaims tis like a fancy everywhere / a sort of living doubt clare wrote about corn crakes in his prose works too and his writings help to clarify the distribution of this rail when it was far more widespread than now
the finnish poet eino leino also wrote about the bird in his poem nocturne
the proverbial use of the corn crake 's call to describe someone with a grating or <unk> voice is illustrated in the quotation thanks to a wee woman with a voice like a corncrake who believed she was an apprentice angel this usage dates from at least the first half of the nineteenth century and continues through to the present


= acute myeloid leukemia =

acute myeloid leukemia ( aml ) also known as acute <unk> leukemia or acute <unk> leukemia ( <unk> ) is a cancer of the myeloid line of blood cells characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells aml is the most common acute leukemia affecting adults and its incidence increases with age although aml is a relatively rare disease accounting for roughly 1 @@ 2 of cancer deaths in the united states its incidence is expected to increase as the population ages
the symptoms of aml are caused by replacement of normal bone marrow with leukemic cells which causes a drop in red blood cells platelets and normal white blood cells these symptoms include fatigue shortness of breath easy bruising and bleeding and increased risk of infection several risk factors and chromosomal abnormalities have been identified but the specific cause is not clear as an acute leukemia aml progresses rapidly and is typically fatal within weeks or months if left untreated
aml has several subtypes treatment and prognosis vary among subtypes aml is cured in 35 40 of people less than 60 years old and 5 15 more than 60 years old older people who are not able to withstand intensive chemotherapy have an average survival of 5 10 months
aml is treated initially with chemotherapy aimed at inducing a remission people may go on to receive additional chemotherapy or a hematopoietic stem cell transplant recent research into the genetics of aml has resulted in the availability of tests that can predict which drug or drugs may work best for a particular person as well as how long that person is likely to survive the treatment and prognosis of aml differ from those of chronic <unk> leukemia ( <unk> ) in part because the cellular differentiation is not the same aml involves higher percentages of <unk> and undifferentiated cells including more blasts ( <unk> <unk> and <unk> )

= = signs and symptoms = =

most signs and symptoms of aml are caused by the replacement of normal blood cells with leukemic cells a lack of normal white blood cell production makes people more susceptible to infections while the leukemic cells themselves are derived from white blood cell precursors they have no infection @@ fighting capacity a drop in red blood cell count ( anemia ) can cause fatigue paleness and shortness of breath a lack of platelets can lead to easy bruising or bleeding with minor trauma
the early signs of aml are often vague and nonspecific and may be similar to those of influenza or other common illnesses some generalized symptoms include fever fatigue weight loss or loss of appetite shortness of breath anemia easy bruising or bleeding petechiae ( flat pin @@ head sized spots under the skin caused by bleeding ) bone and joint pain and persistent or frequent infections
enlargement of the spleen may occur in aml but it is typically mild and asymptomatic <unk> node swelling is rare in aml in contrast to acute lymphoblastic leukemia the skin is involved about 10 of the time in the form of leukemia cutis rarely sweet 's syndrome a paraneoplastic inflammation of the skin can occur with aml
some people with aml may experience swelling of the gums because of infiltration of leukemic cells into the gum tissue rarely the first sign of leukemia may be the development of a solid leukemic mass or tumor outside of the bone marrow called a <unk> occasionally a person may show no symptoms and the leukemia may be discovered incidentally during a routine blood test

= = risk factors = =

a number of risk factors for developing aml have been identified including other blood disorders chemical exposures ionizing radiation and genetics

= = = <unk> = = =

<unk> blood disorders such as myelodysplastic syndrome ( mds ) or myeloproliferative disease ( mps ) can evolve into aml the exact risk depends on the type of mds / mps

= = = chemical exposure = = =

exposure to anticancer chemotherapy in particular alkylating agents can increase the risk of subsequently developing aml the risk is highest about three to five years after chemotherapy other chemotherapy agents specifically <unk> and anthracyclines have also been associated with treatment @@ related leukemias which are often associated with specific chromosomal abnormalities in the leukemic cells
occupational chemical exposure to benzene and other aromatic organic solvents is controversial as a cause of aml <unk> and many of its derivatives are known to be carcinogenic in vitro while some studies have suggested a link between occupational exposure to benzene and increased risk of aml others have suggested the attributable risk if any is slight

= = = radiation = = =

high amounts of ionizing radiation exposure can increase the risk of aml survivors of the atomic bombings of hiroshima and nagasaki had an increased rate of aml as did radiologists exposed to high levels of x @@ rays prior to the adoption of modern radiation safety practices people treated with ionizing radiation after treatment for prostate cancer non @@ hodgkin lymphoma lung cancer and breast cancer have the highest chance of acquiring aml but this increased risk returns to the background risk observed in the general population after 12 years

= = = genetics = = =

a hereditary risk for aml appears to exist multiple cases of aml developing in a family at a rate higher than predicted by chance alone have been reported several congenital conditions may increase the risk of leukemia the most common is probably down syndrome which is associated with a 10 to 18 @@ fold increase in the risk of aml

= = diagnosis = =

the first clue to a diagnosis of aml is typically an abnormal result on a complete blood count while an excess of abnormal white blood cells ( <unk> ) is a common finding and leukemic blasts are sometimes seen aml can also present with isolated decreases in platelets red blood cells or even with a low white blood cell count ( leukopenia ) while a presumptive diagnosis of aml can be made by examination of the peripheral blood smear when there are circulating leukemic blasts a definitive diagnosis usually requires an adequate bone marrow aspiration and biopsy
marrow or blood is examined under light microscopy as well as flow cytometry to diagnose the presence of leukemia to differentiate aml from other types of leukemia ( eg acute lymphoblastic leukemia all ) and to classify the subtype of disease a sample of marrow or blood is typically also tested for chromosomal abnormalities by routine cytogenetics or fluorescent in situ hybridization genetic studies may also be performed to look for specific mutations in genes such as flt3 <unk> and kit which may influence the outcome of the disease
<unk> stains on blood and bone marrow smears are helpful in the distinction of aml from all and in subclassification of aml the combination of a myeloperoxidase or sudan black stain and a nonspecific esterase stain will provide the desired information in most cases the myeloperoxidase or sudan black reactions are most useful in establishing the identity of aml and distinguishing it from all the nonspecific esterase stain is used to identify a <unk> component in <unk> and to distinguish a poorly differentiated <unk> leukemia from all
the diagnosis and classification of aml can be challenging and should be performed by a qualified <unk> or hematologist in straightforward cases the presence of certain morphologic features ( such as auer rods ) or specific flow cytometry results can distinguish aml from other leukemias however in the absence of such features diagnosis may be more difficult
the two most commonly used classification <unk> for aml are the older french @@ american @@ british ( fab ) system and the newer world health organization ( who ) system according to the widely used who criteria the diagnosis of aml is established by demonstrating involvement of more than 20 of the blood and / or bone marrow by leukemic <unk> except in the three best prognosis forms of aml with recurrent genetic abnormalities ( t ( 8 21 ) <unk> ( 16 ) and t ( 15 17 ) ) in which the presence of the genetic abnormality is diagnostic irrespective of blast percent the french american british ( fab ) classification is a bit more stringent requiring a blast percentage of at least 30 in bone marrow ( bm ) or peripheral blood ( pb ) for the diagnosis of aml aml must be carefully differentiated from <unk> conditions such as myelodysplastic or myeloproliferative syndromes which are treated differently
because acute promyelocytic leukemia ( apl ) has the highest <unk> and requires a unique form of treatment it is important to quickly establish or exclude the diagnosis of this subtype of leukemia fluorescent in situ hybridization performed on blood or bone marrow is often used for this purpose as it readily identifies the chromosomal translocation [ t ( 15 17 ) ( <unk> <unk> ) ] that characterizes apl there is also a need to molecularly detect the presence of pml / <unk> fusion protein which is an oncogenic product of that translocation

= = = world health organization = = =

the who 2008 classification of acute myeloid leukemia attempts to be more clinically useful and to produce more meaningful prognostic information than the fab criteria each of the who categories contains numerous descriptive subcategories of interest to the <unk> and oncologist however most of the clinically significant information in the who schema is communicated via categorization into one of the subtypes listed below
the who subtypes of aml are
acute leukemias of ambiguous lineage ( also known as mixed phenotype or <unk> acute leukemia ) occur when the leukemic cells can not be classified as either myeloid or lymphoid cells or where both types of cells are present

= = = french @@ american @@ british = = =

the french @@ american @@ british ( fab ) classification system divides aml into eight subtypes m0 through to m7 based on the type of cell from which the leukemia developed and its degree of maturity this is done by examining the appearance of the malignant cells with light microscopy and / or by using cytogenetics to characterize any underlying chromosomal abnormalities the subtypes have varying prognoses and responses to therapy although the who classification ( see above ) may be more useful the fab system is still widely used
eight fab subtypes were proposed in 1976
the morphologic subtypes of aml also include rare types not included in the fab system such as acute basophilic leukemia which was proposed as a ninth subtype m8 in 1999

= = pathophysiology = =

the malignant cell in aml is the myeloblast in normal <unk> the myeloblast is an immature precursor of myeloid white blood cells a normal myeloblast will gradually mature into a mature white blood cell in aml though a single myeloblast accumulates genetic changes which freeze the cell in its immature state and prevent differentiation such a mutation alone does not cause leukemia however when such a differentiation arrest is combined with other mutations which disrupt genes controlling proliferation the result is the uncontrolled growth of an immature clone of cells leading to the clinical entity of aml
much of the diversity and heterogeneity of aml stems is because leukemic transformation can occur at a number of different steps along the differentiation pathway modern classification schemes for aml recognize the characteristics and behavior of the leukemic cell ( and the leukemia ) may depend on the stage at which differentiation was halted
specific cytogenetic abnormalities can be found in many people with aml the types of chromosomal abnormalities often have prognostic significance the chromosomal translocations encode abnormal fusion proteins usually transcription factors whose altered properties may cause the differentiation arrest for example in acute promyelocytic leukemia the t ( 15 17 ) translocation produces a pml @@ <unk> fusion protein which binds to the retinoic acid receptor element in the promoters of several myeloid @@ specific genes and inhibits myeloid differentiation
the clinical signs and symptoms of aml result from the growth of leukemic clone cells which tends to displace or interfere with the development of normal blood cells in the bone marrow this leads to neutropenia anemia and thrombocytopenia the symptoms of aml are in turn often due to the low numbers of these normal blood elements in rare cases people with aml can develop a <unk> or solid tumor of leukemic cells outside the bone marrow which can cause various symptoms depending on its location
an important pathophysiological mechanism of <unk> in aml is the epigenetic induction of <unk> by genetic mutations that alter the function of epigenetic enzymes such as the dna <unk> <unk> and the metabolic enzymes <unk> and <unk> which lead to the generation of a novel <unk> d @@ 2 @@ <unk> which inhibits the activity of epigenetic enzymes such as <unk> the hypothesis is that such epigenetic mutations lead to the silencing of tumor suppressor genes and / or the activation of proto @@ oncogenes

= = treatment = =

first @@ line treatment of aml consists primarily of chemotherapy and is divided into two phases induction and postremission ( or consolidation ) therapy the goal of induction therapy is to achieve a complete remission by reducing the number of leukemic cells to an undetectable level the goal of consolidation therapy is to eliminate any residual undetectable disease and achieve a cure <unk> stem cell transplantation is usually considered if induction chemotherapy fails or after a person relapses although transplantation is also sometimes used as front @@ line therapy for people with high @@ risk disease efforts to use tyrosine kinase inhibitors in aml continue

= = = induction = = =

all fab subtypes except m3 are usually given induction chemotherapy with cytarabine ( ara @@ c ) and an anthracycline ( most often daunorubicin ) this induction chemotherapy regimen is known as 7 + 3 ( or 3 + 7 ) because the cytarabine is given as a continuous iv infusion for seven consecutive days while the anthracycline is given for three consecutive days as an iv push up to 70 of people with aml will achieve a remission with this protocol other alternative induction regimens including high @@ dose cytarabine alone flag @@ like regimens or investigational agents may also be used because of the toxic effects of therapy including <unk> and an increased risk of infection induction chemotherapy may not be offered to the very elderly and the options may include less intense chemotherapy or palliative care
the m3 subtype of aml also known as acute promyelocytic leukemia ( apl ) is almost universally treated with the drug all @@ trans @@ retinoic acid ( atra ) in addition to induction chemotherapy usually an anthracycline care must be taken to prevent disseminated intravascular coagulation ( dic ) complicating the treatment of apl when the <unk> release the contents of their granules into the peripheral circulation apl is eminently curable with well @@ documented treatment protocols
the goal of the induction phase is to reach a complete remission complete remission does not mean the disease has been cured rather it signifies no disease can be detected with available diagnostic methods complete remission is obtained in about 50 75 of newly diagnosed adults although this may vary based on the prognostic factors described above the length of remission depends on the prognostic features of the original leukemia in general all remissions will fail without additional consolidation therapy

= = = consolidation = = =

even after complete remission is achieved leukemic cells likely remain in numbers too small to be detected with current diagnostic techniques if no further postremission or consolidation therapy is given almost all people with aml will eventually relapse therefore more therapy is necessary to eliminate <unk> disease and prevent relapse that is to achieve a cure
the specific type of postremission therapy is individualized based on a person 's prognostic factors ( see above ) and general health for good @@ prognosis leukemias ( ie <unk> ( 16 ) t ( 8 21 ) and t ( 15 17 ) ) people will typically undergo an additional three to five courses of intensive chemotherapy known as consolidation chemotherapy for people at high risk of relapse ( eg those with high @@ risk cytogenetics underlying mds or therapy @@ related aml ) <unk> stem cell transplantation is usually recommended if the person is able to tolerate a transplant and has a suitable donor the best postremission therapy for intermediate @@ risk aml ( normal cytogenetics or cytogenetic changes not falling into good @@ risk or high @@ risk groups ) is less clear and depends on the specific situation including the age and overall health of the person the person 's values and whether a suitable stem cell donor is available
for people who are not eligible for a stem cell transplant immunotherapy with a combination of histamine <unk> ( <unk> ) and interleukin 2 ( <unk> ) after the completion of consolidation has been shown to reduce the absolute relapse risk by 14 translating to a 50 increase in the likelihood of maintained remission

= = = <unk> aml = = =

for people with relapsed aml the only proven potentially curative therapy is a hematopoietic stem cell transplant if one has not already been performed in 2000 the monoclonal antibody @@ linked cytotoxic agent <unk> <unk> ( <unk> ) was approved in the united states for people aged more than 60 years with relapsed aml who are not candidates for high @@ dose chemotherapy this drug was voluntarily withdrawn from the market by its manufacturer pfizer in 2010
since treatment options for relapsed aml are so limited palliative care or enrolment in a clinical trial may be offered
for relapsed acute promyelocytic leukemia ( apl ) arsenic trioxide is approved by the us fda like atra arsenic trioxide does not work with other subtypes of aml

most rails are secretive wetland birds that have made little cultural impression but as a formerly common farmland bird with a loud nocturnal call that sometimes led to disturbed sleep for rural dwellers the corn crake has acquired a variety of folk names and some commemoration in literature

= = = names = = =

the favoured name for this species among naturalists has changed over the years with <unk> and variants of corncrake being preferred at various times crake gallinule also had a period of popularity between 1768 and 1813 the originally older scots <unk> was popularised by thomas bewick who used this term in his 1797 a history of british birds other scots names include corn <unk> and <unk> the latter term like king of the quail grass quail the french roi de caille and the german <unk> refer to the association with the small gamebird another name <unk> has been variously interpreted as onomatopoeic or derived from the old norse ager @@ <unk> meaning cock of the field variants include drake drake hen and gorse drake

= = = in literature = = =

corn crakes are the subject of three stanzas of the seventeenth century poet andrew marvell 's upon appleton house written in 1651 about the north yorkshire country estate of thomas fairfax the narrator depicts the scene of a mower cutting the grass before his whistling <unk> unknowingly carves the rail the farmhand draws out the scythe all bloody from its breast and does the stroke detest it continues with a stanza that demonstrates the problematic nature of the corn crake 's nesting habits

john clare the nineteenth @@ century english poet based in northamptonshire wrote the landrail a semi @@ comic piece which is primarily about the difficulty of seeing corn crakes as opposed to hearing them in the fourth verse he exclaims tis like a fancy everywhere / a sort of living doubt clare wrote about corn crakes in his prose works too and his writings help to clarify the distribution of this rail when it was far more widespread than now

the finnish poet eino leino also wrote about the bird in his poem nocturne

the proverbial use of the corn crake 's call to describe someone with a grating or <unk> voice is illustrated in the quotation thanks to a wee woman with a voice like a corncrake who believed she was an apprentice angel this usage dates from at least the first half of the nineteenth century and continues through to the present

= acute myeloid leukemia =

acute myeloid leukemia ( aml ) also known as acute <unk> leukemia or acute <unk> leukemia ( <unk> ) is a cancer of the myeloid line of blood cells characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells aml is the most common acute leukemia affecting adults and its incidence increases with age although aml is a relatively rare disease accounting for roughly 1 @@ 2 of cancer deaths in the united states its incidence is expected to increase as the population ages

the symptoms of aml are caused by replacement of normal bone marrow with leukemic cells which causes a drop in red blood cells platelets and normal white blood cells these symptoms include fatigue shortness of breath easy bruising and bleeding and increased risk of infection several risk factors and chromosomal abnormalities have been identified but the specific cause is not clear as an acute leukemia aml progresses rapidly and is typically fatal within weeks or months if left untreated

aml has several subtypes treatment and prognosis vary among subtypes aml is cured in 35 40 of people less than 60 years old and 5 15 more than 60 years old older people who are not able to withstand intensive chemotherapy have an average survival of 5 10 months

aml is treated initially with chemotherapy aimed at inducing a remission people may go on to receive additional chemotherapy or a hematopoietic stem cell transplant recent research into the genetics of aml has resulted in the availability of tests that can predict which drug or drugs may work best for a particular person as well as how long that person is likely to survive the treatment and prognosis of aml differ from those of chronic <unk> leukemia ( <unk> ) in part because the cellular differentiation is not the same aml involves higher percentages of <unk> and undifferentiated cells including more blasts ( <unk> <unk> and <unk> )

= = signs and symptoms = =

most signs and symptoms of aml are caused by the replacement of normal blood cells with leukemic cells a lack of normal white blood cell production makes people more susceptible to infections while the leukemic cells themselves are derived from white blood cell precursors they have no infection @@ fighting capacity a drop in red blood cell count ( anemia ) can cause fatigue paleness and shortness of breath a lack of platelets can lead to easy bruising or bleeding with minor trauma

the early signs of aml are often vague and nonspecific and may be similar to those of influenza or other common illnesses some generalized symptoms include fever fatigue weight loss or loss of appetite shortness of breath anemia easy bruising or bleeding petechiae ( flat pin @@ head sized spots under the skin caused by bleeding ) bone and joint pain and persistent or frequent infections

enlargement of the spleen may occur in aml but it is typically mild and asymptomatic <unk> node swelling is rare in aml in contrast to acute lymphoblastic leukemia the skin is involved about 10 of the time in the form of leukemia cutis rarely sweet 's syndrome a paraneoplastic inflammation of the skin can occur with aml

some people with aml may experience swelling of the gums because of infiltration of leukemic cells into the gum tissue rarely the first sign of leukemia may be the development of a solid leukemic mass or tumor outside of the bone marrow called a <unk> occasionally a person may show no symptoms and the leukemia may be discovered incidentally during a routine blood test

= = risk factors = =

a number of risk factors for developing aml have been identified including other blood disorders chemical exposures ionizing radiation and genetics

= = = <unk> = = =

<unk> blood disorders such as myelodysplastic syndrome ( mds ) or myeloproliferative disease ( mps ) can evolve into aml the exact risk depends on the type of mds / mps

= = = chemical exposure = = =

exposure to anticancer chemotherapy in particular alkylating agents can increase the risk of subsequently developing aml the risk is highest about three to five years after chemotherapy other chemotherapy agents specifically <unk> and anthracyclines have also been associated with treatment @@ related leukemias which are often associated with specific chromosomal abnormalities in the leukemic cells

occupational chemical exposure to benzene and other aromatic organic solvents is controversial as a cause of aml <unk> and many of its derivatives are known to be carcinogenic in vitro while some studies have suggested a link between occupational exposure to benzene and increased risk of aml others have suggested the attributable risk if any is slight

= = = radiation = = =

high amounts of ionizing radiation exposure can increase the risk of aml survivors of the atomic bombings of hiroshima and nagasaki had an increased rate of aml as did radiologists exposed to high levels of x @@ rays prior to the adoption of modern radiation safety practices people treated with ionizing radiation after treatment for prostate cancer non @@ hodgkin lymphoma lung cancer and breast cancer have the highest chance of acquiring aml but this increased risk returns to the background risk observed in the general population after 12 years

= = = genetics = = =

a hereditary risk for aml appears to exist multiple cases of aml developing in a family at a rate higher than predicted by chance alone have been reported several congenital conditions may increase the risk of leukemia the most common is probably down syndrome which is associated with a 10 to 18 @@ fold increase in the risk of aml

= = diagnosis = =

the first clue to a diagnosis of aml is typically an abnormal result on a complete blood count while an excess of abnormal white blood cells ( <unk> ) is a common finding and leukemic blasts are sometimes seen aml can also present with isolated decreases in platelets red blood cells or even with a low white blood cell count ( leukopenia ) while a presumptive diagnosis of aml can be made by examination of the peripheral blood smear when there are circulating leukemic blasts a definitive diagnosis usually requires an adequate bone marrow aspiration and biopsy

marrow or blood is examined under light microscopy as well as flow cytometry to diagnose the presence of leukemia to differentiate aml from other types of leukemia ( eg acute lymphoblastic leukemia all ) and to classify the subtype of disease a sample of marrow or blood is typically also tested for chromosomal abnormalities by routine cytogenetics or fluorescent in situ hybridization genetic studies may also be performed to look for specific mutations in genes such as flt3 <unk> and kit which may influence the outcome of the disease

<unk> stains on blood and bone marrow smears are helpful in the distinction of aml from all and in subclassification of aml the combination of a myeloperoxidase or sudan black stain and a nonspecific esterase stain will provide the desired information in most cases the myeloperoxidase or sudan black reactions are most useful in establishing the identity of aml and distinguishing it from all the nonspecific esterase stain is used to identify a <unk> component in <unk> and to distinguish a poorly differentiated <unk> leukemia from all

the diagnosis and classification of aml can be challenging and should be performed by a qualified <unk> or hematologist in straightforward cases the presence of certain morphologic features ( such as auer rods ) or specific flow cytometry results can distinguish aml from other leukemias however in the absence of such features diagnosis may be more difficult

the two most commonly used classification <unk> for aml are the older french @@ american @@ british ( fab ) system and the newer world health organization ( who ) system according to the widely used who criteria the diagnosis of aml is established by demonstrating involvement of more than 20 of the blood and / or bone marrow by leukemic <unk> except in the three best prognosis forms of aml with recurrent genetic abnormalities ( t ( 8 21 ) <unk> ( 16 ) and t ( 15 17 ) ) in which the presence of the genetic abnormality is diagnostic irrespective of blast percent the french american british ( fab ) classification is a bit more stringent requiring a blast percentage of at least 30 in bone marrow ( bm ) or peripheral blood ( pb ) for the diagnosis of aml aml must be carefully differentiated from <unk> conditions such as myelodysplastic or myeloproliferative syndromes which are treated differently

because acute promyelocytic leukemia ( apl ) has the highest <unk> and requires a unique form of treatment it is important to quickly establish or exclude the diagnosis of this subtype of leukemia fluorescent in situ hybridization performed on blood or bone marrow is often used for this purpose as it readily identifies the chromosomal translocation [ t ( 15 17 ) ( <unk> <unk> ) ] that characterizes apl there is also a need to molecularly detect the presence of pml / <unk> fusion protein which is an oncogenic product of that translocation

= = = world health organization = = =

the who 2008 classification of acute myeloid leukemia attempts to be more clinically useful and to produce more meaningful prognostic information than the fab criteria each of the who categories contains numerous descriptive subcategories of interest to the <unk> and oncologist however most of the clinically significant information in the who schema is communicated via categorization into one of the subtypes listed below

the who subtypes of aml are

acute leukemias of ambiguous lineage ( also known as mixed phenotype or <unk> acute leukemia ) occur when the leukemic cells can not be classified as either myeloid or lymphoid cells or where both types of cells are present

= = = french @@ american @@ british = = =

the french @@ american @@ british ( fab ) classification system divides aml into eight subtypes m0 through to m7 based on the type of cell from which the leukemia developed and its degree of maturity this is done by examining the appearance of the malignant cells with light microscopy and / or by using cytogenetics to characterize any underlying chromosomal abnormalities the subtypes have varying prognoses and responses to therapy although the who classification ( see above ) may be more useful the fab system is still widely used

eight fab subtypes were proposed in 1976

the morphologic subtypes of aml also include rare types not included in the fab system such as acute basophilic leukemia which was proposed as a ninth subtype m8 in 1999

= = pathophysiology = =

the malignant cell in aml is the myeloblast in normal <unk> the myeloblast is an immature precursor of myeloid white blood cells a normal myeloblast will gradually mature into a mature white blood cell in aml though a single myeloblast accumulates genetic changes which freeze the cell in its immature state and prevent differentiation such a mutation alone does not cause leukemia however when such a differentiation arrest is combined with other mutations which disrupt genes controlling proliferation the result is the uncontrolled growth of an immature clone of cells leading to the clinical entity of aml

much of the diversity and heterogeneity of aml stems is because leukemic transformation can occur at a number of different steps along the differentiation pathway modern classification schemes for aml recognize the characteristics and behavior of the leukemic cell ( and the leukemia ) may depend on the stage at which differentiation was halted

specific cytogenetic abnormalities can be found in many people with aml the types of chromosomal abnormalities often have prognostic significance the chromosomal translocations encode abnormal fusion proteins usually transcription factors whose altered properties may cause the differentiation arrest for example in acute promyelocytic leukemia the t ( 15 17 ) translocation produces a pml @@ <unk> fusion protein which binds to the retinoic acid receptor element in the promoters of several myeloid @@ specific genes and inhibits myeloid differentiation

the clinical signs and symptoms of aml result from the growth of leukemic clone cells which tends to displace or interfere with the development of normal blood cells in the bone marrow this leads to neutropenia anemia and thrombocytopenia the symptoms of aml are in turn often due to the low numbers of these normal blood elements in rare cases people with aml can develop a <unk> or solid tumor of leukemic cells outside the bone marrow which can cause various symptoms depending on its location

an important pathophysiological mechanism of <unk> in aml is the epigenetic induction of <unk> by genetic mutations that alter the function of epigenetic enzymes such as the dna <unk> <unk> and the metabolic enzymes <unk> and <unk> which lead to the generation of a novel <unk> d @@ 2 @@ <unk> which inhibits the activity of epigenetic enzymes such as <unk> the hypothesis is that such epigenetic mutations lead to the silencing of tumor suppressor genes and / or the activation of proto @@ oncogenes

= = treatment = =

first @@ line treatment of aml consists primarily of chemotherapy and is divided into two phases induction and postremission ( or consolidation ) therapy the goal of induction therapy is to achieve a complete remission by reducing the number of leukemic cells to an undetectable level the goal of consolidation therapy is to eliminate any residual undetectable disease and achieve a cure <unk> stem cell transplantation is usually considered if induction chemotherapy fails or after a person relapses although transplantation is also sometimes used as front @@ line therapy for people with high @@ risk disease efforts to use tyrosine kinase inhibitors in aml continue

= = = induction = = =

all fab subtypes except m3 are usually given induction chemotherapy with cytarabine ( ara @@ c ) and an anthracycline ( most often daunorubicin ) this induction chemotherapy regimen is known as 7 + 3 ( or 3 + 7 ) because the cytarabine is given as a continuous iv infusion for seven consecutive days while the anthracycline is given for three consecutive days as an iv push up to 70 of people with aml will achieve a remission with this protocol other alternative induction regimens including high @@ dose cytarabine alone flag @@ like regimens or investigational agents may also be used because of the toxic effects of therapy including <unk> and an increased risk of infection induction chemotherapy may not be offered to the very elderly and the options may include less intense chemotherapy or palliative care

the m3 subtype of aml also known as acute promyelocytic leukemia ( apl ) is almost universally treated with the drug all @@ trans @@ retinoic acid ( atra ) in addition to induction chemotherapy usually an anthracycline care must be taken to prevent disseminated intravascular coagulation ( dic ) complicating the treatment of apl when the <unk> release the contents of their granules into the peripheral circulation apl is eminently curable with well @@ documented treatment protocols

the goal of the induction phase is to reach a complete remission complete remission does not mean the disease has been cured rather it signifies no disease can be detected with available diagnostic methods complete remission is obtained in about 50 75 of newly diagnosed adults although this may vary based on the prognostic factors described above the length of remission depends on the prognostic features of the original leukemia in general all remissions will fail without additional consolidation therapy

= = = consolidation = = =

even after complete remission is achieved leukemic cells likely remain in numbers too small to be detected with current diagnostic techniques if no further postremission or consolidation therapy is given almost all people with aml will eventually relapse therefore more therapy is necessary to eliminate <unk> disease and prevent relapse that is to achieve a cure

the specific type of postremission therapy is individualized based on a person 's prognostic factors ( see above ) and general health for good @@ prognosis leukemias ( ie <unk> ( 16 ) t ( 8 21 ) and t ( 15 17 ) ) people will typically undergo an additional three to five courses of intensive chemotherapy known as consolidation chemotherapy for people at high risk of relapse ( eg those with high @@ risk cytogenetics underlying mds or therapy @@ related aml ) <unk> stem cell transplantation is usually recommended if the person is able to tolerate a transplant and has a suitable donor the best postremission therapy for intermediate @@ risk aml ( normal cytogenetics or cytogenetic changes not falling into good @@ risk or high @@ risk groups ) is less clear and depends on the specific situation including the age and overall health of the person the person 's values and whether a suitable stem cell donor is available

for people who are not eligible for a stem cell transplant immunotherapy with a combination of histamine <unk> ( <unk> ) and interleukin 2 ( <unk> ) after the completion of consolidation has been shown to reduce the absolute relapse risk by 14 translating to a 50 increase in the likelihood of maintained remission

= = = <unk> aml = = =

for people with relapsed aml the only proven potentially curative therapy is a hematopoietic stem cell transplant if one has not already been performed in 2000 the monoclonal antibody @@ linked cytotoxic agent <unk> <unk> ( <unk> ) was approved in the united states for people aged more than 60 years with relapsed aml who are not candidates for high @@ dose chemotherapy this drug was voluntarily withdrawn from the market by its manufacturer pfizer in 2010

since treatment options for relapsed aml are so limited palliative care or enrolment in a clinical trial may be offered

for relapsed acute promyelocytic leukemia ( apl ) arsenic trioxide is approved by the us fda like atra arsenic trioxide does not work with other subtypes of aml