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{{Acute myeloid leukemia}}
{{Acute myeloid leukemia}}


{{CMG}}; {{AE}} {{RT}} {{CLG}} {{shyam}}
{{CMG}}; {{AE}} {{RT}}, {{CLG}}, {{shyam}}; {{GRR}} {{Nat}}


==Overview==
==Overview==
Acute myeloid leukemia may be classified according to the [[French-American-British classification | French-American-British (FAB) classification]] and [[World Health Organization]] (WHO).
There are three classification systems for acute myeloid leukemia. These classifications include[[French-American-British classification | French-American-British (FAB)]] , the [[World Health Organization]] (WHO), and the [[European LeukemiaNet]] (ELN) . The original classification was the [[French-American-British classification |French-American-British (FAB) classification]], and the most recent classification was the 2017 European LeukemiaNet (ELN) classification. There are several broad classification schemes for [[Acute promyelocytic leukemia classification|acute promyelocytic leukemia]]. The most well-accepted [[Acute promyelocytic leukemia classification|classification scheme]] is risk-based classification, which categories patients into low-risk, intermediate-risk, or high-risk based on the [[white blood cell]] count and [[platelet]] count. Another classification scheme is based on the origin of the leukemia, which categorized patients as having ''de novo'' or therapy-related disease. A final classification scheme is cytogenetic-based, in which case specific chromosomal abnormalities are used to stratify patients.


== Classification ==
== Classification of Acute myeloid leukemia: ==
There are 3 classifications systems for acute myeloid leukemia. These include the [[French-American-British classification | French-American-British (FAB) classification]], the [[World Health Organization]] (WHO) classification, and the [[European LeukemiaNet]] (ELN) classification.


===French-American-British classification===
===French-American-British classification===
The [[French-American-British classification | French-American-British (FAB) classification]] system divided acute myeloid leukemia into 8 subtypes, M0 through to M7, based on the type of cell from which the leukemia developed and its degree of maturity.  This was done by examining the appearance of the malignant cells under [[light microscopy]] and/or by using [[cytogenetics]] to characterize any underlying chromosomal abnormalities.  The subtypes have varying prognoses and responses to therapy.  Although the [[World Health Organization]] (WHO) classification (see below) may be more useful, the FAB system is still widely used as of mid-2006.
The [[French-American-British classification | French-American-British (FAB) classification]] system divided acute myeloid leukemia into 8 sub-types, M0 through to M7, based on the type of cell from which the leukemia developed and its degree of maturity.  This was done by examining the appearance of the malignant cells under [[light microscopy]] and/or by using [[cytogenetics]] to characterize any underlying chromosomal abnormalities.  The sub-types have varying prognoses and responses to therapy.  Although the [[World Health Organization]] (WHO) classification (see below) may be more useful, the FAB system is still widely used as of mid-2006.


The eight FAB subtypes are:<ref>{{cite journal | author = Bennett J, Catovsky D, Daniel M, Flandrin G, Galton D, Gralnick H, Sultan C | title = Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group | journal = Br J Haematol | volume = 33 | issue = 4 | pages = 451-8 | year = 1976 | pmid = 188440}}</ref>
The eight FAB sub-types are:<ref>{{cite journal | author = Bennett J, Catovsky D, Daniel M, Flandrin G, Galton D, Gralnick H, Sultan C | title = Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group | journal = Br J Haematol | volume = 33 | issue = 4 | pages = 451-8 | year = 1976 | pmid = 188440}}</ref>


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===World Health Organization classification ===
===World Health Organization classification ===
The [[World Health Organization]] (WHO) 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 sub-categories of interest to the [[hematopathologist]] and [[oncologist]]; however, most of the clinically significant information in the WHO schema is communicated via categorization into one of the five subtypes listed below. The 2016 revision of the WHO classification was recently developed.
The [[World Health Organization]] (WHO) 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 sub-categories of interest to [[hematopathologist|hematopathologists]] and [[oncologist|oncologists]]; however, most of the clinically significant information in the WHO schema is communicated via categorization into one of the five sub-types listed below. The 2016 revision of the WHO classification was recently developed.


The subtypes of acute myeloid leukemia are shown below:<ref>{{cite journal | author = Vardiman J, Harris N, Brunning R | title = The World Health Organization (WHO) classification of the myeloid neoplasms | journal = Blood | volume = 100 | issue = 7 | pages = 2292-302 | year = 2002 | pmid = 12239137}}'' [http://www.bloodjournal.org/cgi/content/full/100/7/2292 Full text]''.</ref>
The sub-types of acute myeloid leukemia are shown below:<ref>{{cite journal | author = Vardiman J, Harris N, Brunning R | title = The World Health Organization (WHO) classification of the myeloid neoplasms | journal = Blood | volume = 100 | issue = 7 | pages = 2292-302 | year = 2002 | pmid = 12239137}}'' [http://www.bloodjournal.org/cgi/content/full/100/7/2292 Full text]''.</ref>


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|-
|-
| '''Acute myeloid leukemia with characteristic genetic abnormalities'''
| '''Acute myeloid leukemia with characteristic genetic abnormalities'''
| Includes:
| This category includes:


* AML with translocations between [[chromosome 8]] and 21; [[RUNX1]]/[[RUNX1T1]]<ref name="pmid21629739">{{cite journal| author=Reikvam H, Hatfield KJ, Kittang AO, Hovland R, Bruserud Ø| title=Acute myeloid leukemia with the t(8;21) translocation: clinical consequences and biological implications. | journal=J Biomed Biotechnol | year= 2011 | volume= 2011 | issue=  | pages= 104631 | pmid=21629739 | doi=10.1155/2011/104631 | pmc=3100545 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21629739  }} </ref>
* AML with translocations between [[chromosome 8]] and 21; [[RUNX1]]/[[RUNX1T1]]<ref name="pmid21629739">{{cite journal| author=Reikvam H, Hatfield KJ, Kittang AO, Hovland R, Bruserud Ø| title=Acute myeloid leukemia with the t(8;21) translocation: clinical consequences and biological implications. | journal=J Biomed Biotechnol | year= 2011 | volume= 2011 | issue=  | pages= 104631 | pmid=21629739 | doi=10.1155/2011/104631 | pmc=3100545 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21629739  }} </ref>
* AML with inversions in [[chromosome 16]] &#91;inv(16)&#93; (ICD-O 9871/3); [[CBFB]]/[[MYH11]]
* AML with inversions in [[chromosome 16]]; [[CBFB]]/[[MYH11]]<ref name="pmid29755956">{{cite journal| author=Pulikkan JA, Castilla LH| title=Preleukemia and Leukemia-Initiating Cell Activity in inv(16) Acute Myeloid Leukemia. | journal=Front Oncol | year= 2018 | volume= 8 | issue=  | pages= 129 | pmid=29755956 | doi=10.3389/fonc.2018.00129 | pmc=5932169 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29755956  }} </ref>
* APL with translocations between [[chromosome 15]] and 17 &#91;t(15;17)&#93; (ICD-O 9866/3); [[Retinoic acid receptor alpha|RARA]];[[Promyelocytic leukemia protein|PML]]
* APL with translocations between [[chromosome 15]] and 17; [[Retinoic acid receptor alpha|RARA]];[[Promyelocytic leukemia protein|PML]]<ref name="pmid26660431">{{cite journal| author=Grimwade D, Ivey A, Huntly BJ| title=Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance. | journal=Blood | year= 2016 | volume= 127 | issue= 1 | pages= 29-41 | pmid=26660431 | doi=10.1182/blood-2015-07-604496 | pmc=4705608 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26660431  }} </ref>


Patients with acute myeloid leukemia in this category generally have a high rate of remission and a better prognosis compared to other types of acute myeloid leukemia.
Patients with acute myeloid leukemia in this category generally have a high rate of remission and a better prognosis compared to other types of acute myeloid leukemia.
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|-
|-
| '''Acute myeloid leukemia not otherwise categorized'''
| '''Acute myeloid leukemia not otherwise categorized'''
| Includes subtypes of acute myeloid leukemia that do not fall into the above categories.
| This category includes sub-types of acute myeloid leukemia that do not fall into the above categories.
| {{ICDO|9861|3}}
| {{ICDO|9861|3}}
|}
|}


===European LeukemiaNet classification===
===European LeukemiaNet classification===
The European LeukemiaNet classification is a risk-based classification system that was recently revised in 2017.<ref name="pmid27895058">{{cite journal| author=Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T et al.| title=Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. | journal=Blood | year= 2017 | volume= 129 | issue= 4 | pages= 424-447 | pmid=27895058 | doi=10.1182/blood-2016-08-733196 | pmc=5291965 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27895058  }} </ref>


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| Includes:
| Includes:


* AML with translocations between chromosome 8 and chromosome 21 &#91;t(8;21)&#93; (ICD-O 9896/3); [[RUNX1]]/[[RUNX1T1]]
* AML with translocations between chromosome 8 and chromosome 21; t(8;21); [[RUNX1]]/[[RUNX1T1]]
* AML with inversions in [[chromosome 16]] &#91;inv(16)&#93; (ICD-O 9871/3); [[CBFB]]/[[MYH11]]
* AML with inversions in [[chromosome 16]]; inv(16); [[CBFB]]/[[MYH11]]
* AML with mutant ''NPM1'' and wild-type ''FLT3''
* AML with mutant ''NPM1'' and wild-type ''FLT3''
* AML with biallelic CEBP''alpha'' mutation
* AML with biallelic CEBP''alpha'' mutation
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* AML with mutant ''RUNX1'', mutant ''ASXL1'', or mutant ''TP53''
* AML with mutant ''RUNX1'', mutant ''ASXL1'', or mutant ''TP53''


|}
==Classification of acute promyelocytic leukemia:==
[[Acute promyelocytic leukemia classification|Acute promyelocytic leukemi]]<nowiki/>a is further classified in to the following several classification schemes.
===Based on Risk ===
*'''Low-risk disease''':
**Low-risk disease is defined as the presence of less than 10000 [[white blood cells]] per microliter and greater than 40000 [[platelets]] per microliter in the [[Peripheral blood cell|peripheral blood]].
**Treatment of low-risk [[disease]] involves non-[[chemotherapy]]-based regimens, such as the combination of all trance [[retinoic acid]] and [[arsenic trioxide]].<ref name="pmid25885425">{{cite journal| author=Coombs CC, Tavakkoli M, Tallman MS| title=Acute promyelocytic leukemia: where did we start, where are we now, and the future. | journal=Blood Cancer J | year= 2015 | volume= 5 | issue=  | pages= e304 | pmid=25885425 | doi=10.1038/bcj.2015.25 | pmc=4450325 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25885425  }} </ref>
*'''Intermediate-risk disease''':
**Intermediate-risk [[disease]] is defined as the presence of less than 10000 [[white blood cells]] per [[Microliter|microl]]<nowiki/>[[Microliter|ite]]<nowiki/>r and less than 40000 [[Platelet|plate]]<nowiki/>[[Platelet|lets]] per [[microliter]] in [[Peripheral blood cell|peripheral blood]].<ref name="pmid28352191">{{cite journal| author=McCulloch D, Brown C, Iland H| title=Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives. | journal=Onco Targets Ther | year= 2017 | volume= 10 | issue=  | pages= 1585-1601 | pmid=28352191 | doi=10.2147/OTT.S100513 | pmc=5359123 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28352191  }} </ref>
*'''High-risk disease''':
**High-risk [[disease]] is defined as the presence of greater than 10000 [[white blood cells]] per [[microliter]] in [[peripheral blood]], regardless of the [[platelet]] count.
**[[Platelet]] count is typically less than 40,000 [[Cell (biology)|cells]] per [[microliter]], though [[platelet]] count is not a formal [[criterion]] in the [[classification]] of acute promyelocytic leukemia.<ref name="pmid25885425" />
===Based on etiology===
*'''''De novo'' disease''': 
**''[[De novo]]'' acute promyelocytic leukemia is the most common sub-type.
**This refers to development of the [[disease]] in the absence of prior [[cytotoxic]] [[therapy]] or prior precursor conditions.
**''[[De novo]]'' acute promyelocytic leukemia is due to a sporadic events in [[Cell (biology)|cells]], without prior [[DNA]] damaging insults. This is in contrast to [[therapy]]-related [[disease]].
*'''Therapy-related disease''':
**Therapy-related [[disease]] refers to the development of acute promyelocytic leukemia in-[[Patient|patients]] who were previously treated with [[DNA]]-damaging or [[genotoxic]] agents for other conditions, such as other [[Cancer|cancers]].
**The most common [[DNA]]-damaging agents that cause therapy-associated acute promyelocytic leukemia are [[topoisomerase]] inhibitors and [[Alkylating agent|alkylating agents]].
**Therapy-related acute promyelocytic leukemia is typically seen in [[Patient|patients]] with a history of [[breast cancer]] who received cyclophosphamide or patients with a history of a [[germ cell tumor]] who have received [[etoposide]].
**The [[prognosis]] of [[therapy]]-related [[disease]] is worse than that of ''[[de novo]]'' [[disease]], with a 5-year survival of less than 10 years. The 4-year overall survival for [[therapy]]-related [[disease]] is 24.5%, compared to 39.5% for ''[[de novo]]'' [[disease]].<ref name="pmid25892894">{{cite journal| author=Zhang YC, Zhou YQ, Yan B, Shi J, Xiu LJ, Sun YW et al.| title=Secondary acute promyelocytic leukemia following chemotherapy for gastric cancer: a case report. | journal=World J Gastroenterol | year= 2015 | volume= 21 | issue= 14 | pages= 4402-7 | pmid=25892894 | doi=10.3748/wjg.v21.i14.4402 | pmc=4394105 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25892894  }} </ref>
{| class="wikitable"
|+
! colspan="2" |'''''Chemotherapeutic agents'''''
|-
|'''''Topoisomerase II inhibitors'':'''
|
*This class of [[chemotherapeutics]] causes early-onset [[leukemia]], with a typical latency of 2-3 years from the receipt of the [[topoisomerase inhibitor]].
*[[Cytogenetics]] from the [[leukemia]] [[diagnosis]] typically shows the ''[[MLL]]'' [[rearrangement]] ([[chromosome]] 11q23).
*There is usually no preceding [[myelodysplastic]] phase; the onset of [[leukemia]] is relatively sudden.<ref name="pmid27621757">{{cite journal| author=Zahid MF, Parnes A, Savani BN, Litzow MR, Hashmi SK| title=Therapy-related myeloid neoplasms - what have we learned so far? | journal=World J Stem Cells | year= 2016 | volume= 8 | issue= 8 | pages= 231-42 | pmid=27621757 | doi=10.4252/wjsc.v8.i8.231 | pmc=4999650 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27621757  }} </ref>
|-
|'''''Alkylating agents'':'''
|
*This class of [[chemotherapeutics]] causes late-onset [[leukemia]], with a typical latency of greater than 7 years from the receipt of the [[alkylating agent]].
*Cytogenetics from the leukemia diagnosis typically shows [[monosomy]] 5 or [[monosomy]] 7.
*[[Mutation|Mutational]] analyses can show a ''[[TP53]]'' [[mutation]]. There is usually a preceding [[myelodysplastic]] phase.<ref name="pmid27621757" />
|-
|'''''Other [[chemotherapeutic agents]]'':'''
|
*Although other [[chemotherapy]] [[Medication|medications]] are not classically associated with therapy-related a[[Promyelocytic leukemia protein|promyelocytleukemiamiaiamia]], there have been cases of such associations.
*In a [[patient]] with [[Stomach cancer|gastric cancer]] treated with [[oxaliplatin]] and [[capecitabine]], acute [[Promyelocytic leukemia protein|promy]][[leukemia]] [[leukemia]] developed after a latency period of 4 years.
*The [[leukemic]] [[Cells (biology)|cells]] had [[Chromosome|chromosomal]] [[abnormalities]], suggesting that the secondary neoplasm was [[chemotherapy]]-induced rather than ''[[de novo]]''.<ref name="pmid25892894" />
|}
===Based on cytogenetics===
*The [[Karyotypes|karyotype]] of most cases of acute promyelocytic leukemia involves the t(15;17) [[translocation]] between the ''PML'' and [[RARA gene|''RARA'' genes]]. However, complex [[Karyotype|karyotypes]] may co-exist in some cases of acute promyelocytic leukemia.<ref name="pmid29541170">{{cite journal| author=Chen C, Huang X, Wang K, Chen K, Gao D, Qian S| title=Early mortality in acute promyelocytic leukemia: Potential predictors. | journal=Oncol Lett | year= 2018 | volume= 15 | issue= 4 | pages= 4061-4069 | pmid=29541170 | doi=10.3892/ol.2018.7854 | pmc=5835847 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29541170  }} </ref>
{| class="wikitable"
|+
! colspan="2" |Cytogenetics
|-
|'''Complex karyotype'''
|
*Complex karyotype is defined as the presence of two or more [[Chromosomal abnormalities|chromosomal abnormities]].
*Complex karyotype acute promyelocytic leukemia is associated with worse prognosis and lower rates of complete remission, similar to complex karyotype [[acute myeloid leukemia]]<ref name="pmid29541170" />.
*Patients with complex karyotype are more likely to have a ''[[TP53]]'' [[mutation]] and are more likely to be resistant to [[chemotherapy]].<ref name="pmid29541170" />
|-
|'''Trisomy 8'''
|
*[[Trisomy]] 8 is characterized by three copies of [[chromosome]] 8 in [[Cell (biology)|cells]].
*This [[Chromosome|chromosomal abnormality]] is commonly found in patients with [[myelodysplastic syndrome]], which is a precursor condition for [[acute myeloid leukemia]].
*Aside from t(15;17), [[trisomy]] 8 is the most frequent [[Chromosome abnormality|chromosomal abnormality]] in acute promyelocytic leukemia.<ref name="pmid29541170" />
|-
|'''Tetraploidy'''
|
*[[Tetraploidy]] is defined as the presence of four sets of [[chromosomes]] in a [[Cell (biology)|cell]].
*[[Tetraploidy]] is generally rare in acute promyelocytic [[leukemia]] and accounts for approximately 0.75% of cases. 
*The [[karyotype]] of most cases of acute promyelocytic leukemia involves the t(15;17) [[Translocations|translocation]] between the ''[[Progressive multifocal leukoencephalopathy|PML]]'' and [[RARA gene|''RARA'' genes]]. 
*However, complex [[Karyotype|karyotypes]] may co-exist in some cases of acute promyelocytic leukemia. 
*[[Polyploidy|Tetraploidy]] in acute promyelocytic leukemia is more commonly associated with [[CD2]] [[expression]] in the [[malignant]] [[cells]]. 
*[[Tetraploidy|Tetraploid]] acute promyelocytic leukemia is mostly sensitive to all-''[[trans]]'' [[retinoic acid]].<ref name="pmid29541170" />
|-
|'''t(8;21)'''
|
*The t(8;21) [[Translocations|translocation]] sometimes co-exists with the t(15;17) [[Chromosomal translocation|translocation]].
*The t(8;21) [[Translocations|translocation]] is more commonly found in [[acute myeloid leukemia]] and involves the juxtaposition of the ''ETO'' (''RUNX1T1'') [[gene]] on [[chromosome]] 8 with ''AML1'' (''[[RUNX1]]'') [[gene]] on [[chromosome]] 21.
*A total of six cases of coexisting t(8;21) and t(15;17) have thus far been described.<ref name="pmid8334990">{{cite journal |vauthors=Miyoshi H, Kozu T, Shimizu K, Enomoto K, Maseki N, Kaneko Y, Kamada N, Ohki M |title=The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript |journal=EMBO J. |volume=12 |issue=7 |pages=2715–21 |date=July 1993 |pmid=8334990 |pmc=413521 |doi= |url=}}</ref>
|}
|}



Latest revision as of 13:02, 11 April 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2], Carlos A Lopez, M.D. [3], Shyam Patel [4]; Grammar Reviewer: Natalie Harpenau, B.S.[5]

Overview

There are three classification systems for acute myeloid leukemia. These classifications include French-American-British (FAB) , the World Health Organization (WHO), and the European LeukemiaNet (ELN) . The original classification was the French-American-British (FAB) classification, and the most recent classification was the 2017 European LeukemiaNet (ELN) classification. There are several broad classification schemes for acute promyelocytic leukemia. The most well-accepted classification scheme is risk-based classification, which categories patients into low-risk, intermediate-risk, or high-risk based on the white blood cell count and platelet count. Another classification scheme is based on the origin of the leukemia, which categorized patients as having de novo or therapy-related disease. A final classification scheme is cytogenetic-based, in which case specific chromosomal abnormalities are used to stratify patients.

Classification of Acute myeloid leukemia:

French-American-British classification

The French-American-British (FAB) classification system divided acute myeloid leukemia into 8 sub-types, M0 through to M7, based on the type of cell from which the leukemia developed and its degree of maturity. This was done by examining the appearance of the malignant cells under light microscopy and/or by using cytogenetics to characterize any underlying chromosomal abnormalities. The sub-types have varying prognoses and responses to therapy. Although the World Health Organization (WHO) classification (see below) may be more useful, the FAB system is still widely used as of mid-2006.

The eight FAB sub-types are:[1]

Type Name Cytogenetics
M0 Minimally differentiated AML
M1 Acute myeloblastic leukemia, without maturation
M2 Acute myeloblastic leukemia, with granulocytic maturation t(8;21)(q22;q22), t(6;9)
M3 Promyelocytic, or Acute promyelocytic leukemia (APL) t(15;17)
M4 Acute myelomonocytic leukemia inv(16)(p13q22), del(16q)
M4eo Myelomonocytic together with bone marrow eosinophilia inv(16), t(16;16)
M5 Acute monoblastic leukemia (M5a) or Acute monocytic leukemia (M5b) del (11q), t(9;11), t(11;19)
M6 Acute erythroid leukemias, including erythroleukemia (M6a) and very rare pure erythroid leukemia (M6b)
M7 Acute megakaryoblastic leukemia t(1;22)

World Health Organization classification

The World Health Organization (WHO) 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 sub-categories of interest to hematopathologists and oncologists; however, most of the clinically significant information in the WHO schema is communicated via categorization into one of the five sub-types listed below. The 2016 revision of the WHO classification was recently developed.

The sub-types of acute myeloid leukemia are shown below:[2]

Name Description ICD-O
Acute myeloid leukemia with characteristic genetic abnormalities This category includes:

Patients with acute myeloid leukemia in this category generally have a high rate of remission and a better prognosis compared to other types of acute myeloid leukemia.

Multiple
Acute myeloid leukemia with multilineage dysplasia This category includes patients who have had a prior myelodysplastic syndrome (MDS) or myeloproliferative disease (MPD) that transforms into acute myeloid leukemia. This category of acute myeloid leukemia occurs most often in elderly patients and often has a worse prognosis. Template:ICDO
Acute myeloid leukemia and MDS, therapy-related This category includes patients who have had prior chemotherapy and/or radiation and subsequently develop acute myeloid leukemia or MDS. These leukemias may be characterized by specific chromosomal abnormalities, and often carry a worse prognosis. Template:ICDO
Acute myeloid leukemia not otherwise categorized This category includes sub-types of acute myeloid leukemia that do not fall into the above categories. Template:ICDO

European LeukemiaNet classification

The European LeukemiaNet classification is a risk-based classification system that was recently revised in 2017.[6]

Name Description
Favorable risk Includes:
  • AML with translocations between chromosome 8 and chromosome 21; t(8;21); RUNX1/RUNX1T1
  • AML with inversions in chromosome 16; inv(16); CBFB/MYH11
  • AML with mutant NPM1 and wild-type FLT3
  • AML with biallelic CEBPalpha mutation
Intermediate risk Includes:
  • AML with mutant NPM1 and mutant FLT3 (FLT3-ITD)
  • AML with wild-type NPM1 and wild-type FLT3 (no FLT3-ITD)
  • AML with translocations between chromosome 9 and chromosome 21 (MLLT3-KMT2A)
  • AML with cytogenetic abnormalities not classified as favorable or adverse
Adverse risk Includes:
  • AML with translocations between chromosome 6 and chromosome 9
  • AML with inversion of chromosome 3
  • AML with translocations involving chromosome 11q23
  • AML with translocations between chromosome 6 and chromosome 9
  • AML with monosomy 5 or 7
  • AML with complex karyotype (2 or more cytogenetic abnormalities)
  • AML with mutant RUNX1, mutant ASXL1, or mutant TP53

Classification of acute promyelocytic leukemia:

Acute promyelocytic leukemia is further classified in to the following several classification schemes.

Based on Risk

Based on etiology

  • De novo disease:
    • De novo acute promyelocytic leukemia is the most common sub-type.
    • This refers to development of the disease in the absence of prior cytotoxic therapy or prior precursor conditions.
    • De novo acute promyelocytic leukemia is due to a sporadic events in cells, without prior DNA damaging insults. This is in contrast to therapy-related disease.
Chemotherapeutic agents
Topoisomerase II inhibitors:
Alkylating agents:
Other chemotherapeutic agents:

Based on cytogenetics

Cytogenetics
Complex karyotype
  • Complex karyotype is defined as the presence of two or more chromosomal abnormities.
  • Complex karyotype acute promyelocytic leukemia is associated with worse prognosis and lower rates of complete remission, similar to complex karyotype acute myeloid leukemia[11].
  • Patients with complex karyotype are more likely to have a TP53 mutation and are more likely to be resistant to chemotherapy.[11]
Trisomy 8
Tetraploidy
t(8;21)

References

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