Changes

[[AML|Acute Myeloid Leukemia]]

[[AML|Acute Myeloid Leukemia]]

[[Myeloid Proliferations Associated with Down Syndrome]]

[[HAEM4:Myeloid Proliferations Associated with Down Syndrome]]

==Cancer Sub-Classification / Subtype==

==Cancer Sub-Classification / Subtype==

==Definition / Description of Disease==

==Definition / Description of Disease==

This is a distinct entity in the World Health Organization (WHO) classification system within the section of [[Myeloid Proliferations Associated with Down Syndrome]]<ref name=":0">Arber DA, et al., (2017). Myeloid proliferations associated with Down syndrome, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p170-171.</ref>.  

This is a distinct entity in the World Health Organization (WHO) classification system within the section of [[HAEM4:Myeloid Proliferations Associated with Down Syndrome]]<ref name=":0">Arber DA, et al., (2017). Myeloid proliferations associated with Down syndrome, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p170-171.</ref>.  

In Down Syndrome (DS), most cases of AML are acute megakaryoblastic leukemia (AMKL). AMKL accounts for >50% of all cases of acute leukemia in DS beyond the  neonatal period. AML often follows a myelodysplastic syndrome (MDS)-like phase. In DS individuals, there is no biological difference between MDS and overt AML<ref name=":0" />.

In Down Syndrome (DS), most cases of AML are acute megakaryoblastic leukemia (AMKL). AMKL accounts for >50% of all cases of acute leukemia in DS beyond the  neonatal period. AML often follows a myelodysplastic syndrome (MDS)-like phase. In DS individuals, there is no biological difference between MDS and overt AML<ref name=":0" />.

Acute megakaryoblastic leukemia (AMKL) is a subtype of acute myeloid leukemia (AML) characterized by abnormal megakaryoblasts that express platelet-specific surface glycoprotein. Bone marrow biopsy frequently demonstrates extensive myelofibrosis, often making aspiration in these patients difficult. AMKL comprises between 4% and 15% of pediatric AML patients. It is divided into 2 major subgroups: AMKL in patients with Down syndrome (DS-AMKL) and AMKL in patients without DS (non-DS-AMKL). AMKL is the most frequent type of AML in children with DS, and the incidence in these patients is 500-fold higher than in the general population.

Acute megakaryoblastic leukemia (AMKL) is a subtype of acute myeloid leukemia (AML) characterized by abnormal megakaryoblasts that express platelet-specific surface glycoprotein. Bone marrow biopsy frequently demonstrates extensive myelofibrosis, often making aspiration in these patients difficult. AMKL comprises between 4% and 15% of pediatric AML patients. It is divided into 2 major subgroups: AMKL in patients with Down syndrome (DS-AMKL) and AMKL in patients without DS (non-DS-AMKL). AMKL is the most frequent type of AML in children with DS, and the incidence in these patients is 500-fold higher than in the general population.

DS-AMKL is biologically and clinically distinct from non-DS-AMKL. Pediatric '''''non'''''-DS-AMKL (i.e. AMKL NOT associated with Down syndrome) occurs in a heterogenous group of patients, a significant proportion of whom carry chimeric oncogenes including RBM15-MKL1, which represents the distinct entity [http://www.ccga.io/index.php/Acute_Myeloid_Leukemia_(AML)_Megakaryoblastic_with_t(1;22)(p13.3;q13.1);RBM15-MKL1 Acute Myeloid Leukemia (AML) Megakaryoblastic with t(1;22)(p13.3;q13.1);RBM15-MKL1], CBFA2T3-GLIS2, NUP98-KDM5A, and [[KMT2A]](MLL) rearrangements, which are not found in DS-AMKL<ref name=":1">{{Cite journal|last=Gruber|first=Tanja A.|last2=Downing|first2=James R.|date=2015|title=The biology of pediatric acute megakaryoblastic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/26186939|journal=Blood|volume=126|issue=8|pages=943–949|doi=10.1182/blood-2015-05-567859|issn=1528-0020|pmc=4551356|pmid=26186939}}</ref>.

DS-AMKL is biologically and clinically distinct from non-DS-AMKL. Pediatric '''''non'''''-DS-AMKL (i.e. AMKL NOT associated with Down syndrome) occurs in a heterogenous group of patients, a significant proportion of whom carry chimeric oncogenes including RBM15-MKL1, which represents the distinct entity [http://www.ccga.io/index.php/HAEM5:Acute_myeloid_leukaemia_with_RBM15::MRTFA_fusion Acute Myeloid Leukemia (AML) Megakaryoblastic with t(1;22)(p13.3;q13.1);RBM15-MKL1], CBFA2T3-GLIS2, NUP98-KDM5A, and [[KMT2A]](MLL) rearrangements, which are not found in DS-AMKL<ref name=":1">{{Cite journal|last=Gruber|first=Tanja A.|last2=Downing|first2=James R.|date=2015|title=The biology of pediatric acute megakaryoblastic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/26186939|journal=Blood|volume=126|issue=8|pages=943–949|doi=10.1182/blood-2015-05-567859|issn=1528-0020|pmc=4551356|pmid=26186939}}</ref>.

==Synonyms / Terminology==

==Synonyms / Terminology==

==Other Information==

==Other Information==

Also see: [http://www.ccga.io/index.php/Transient_Abnormal_Myelopoiesis_(TAM)_Associated_with_Down_Syndrome Transient Abnormal Myelopoiesis (TAM) Associated with Down Syndrome]

Also see: [http://www.ccga.io/index.php/HAEM5:Myeloid_proliferations_associated_with_Down_syndrome Transient Abnormal Myelopoiesis (TAM) Associated with Down Syndrome]

==Links==

==Links==