HAEM5:Myeloid proliferations associated with Down syndrome: Difference between revisions

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Other relevent pages include: [[HAEM4:Transient Abnormal Myelopoiesis (TAM) Associated with Down Syndrome]], [[HAEM4:Myeloid Leukemia Associated with Down Syndrome]]

Linda D Cooley, MD, MBA, Children's Mercy Hospital, Kansas City, MO

==WHO Classification of Disease==

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|Acceptable

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|Not Recommended

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not applicable

* Chromosomal Rearrangements (Gene Fusions)

* Individual Region Genomic Gain/Loss/LOH

The disease evolution of TAM and DS-AMKL is currently conceived as a sequential multistep process of leukemogenesis. Trisomy 21 represents the critical “initiating” event. ''GATA1'' mutation reflects a “secondary hit” to fetal liver hematopoiesis, particularly megakaryocytic-erythroid progenitors, that leads to TAM and confers some selective advantage.  

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|<span class="blue-text">EXAMPLE:</span>

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not applicable

!Chromosomal Pattern

!Molecular Pathogenesis

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|<span class="blue-text">EXAMPLE:</span>

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Constitutional trisomy 21 or mosaic constitutional trisomy 21

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|<span class="blue-text">EXAMPLE:</span>''EGFR''

|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

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In addition to trisomy 21, acquired ''GATA1'' mutations are present in blast cells of TAM [1].

In normal human development, the liver is the primary site of fetal (in utero) hematopoiesis. With birth, the hepatic microenvironment changes such that liver hematopoiesis is down-regulated while bone marrow simultaneously assumes this primary functionality. Given the clinical and laboratory manifestations of TAM, which include leukocytosis and circulating megakaryoblasts, often with hepatomegaly, TAM reflects perturbation of this normal developmental process. Transient abnormal myelopoiesis may arise in utero within the fetal liver with “spontaneous resolution” reflecting the natural process of hepatic hematopoietic down-regulation. 

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==Notes==

          

<nowiki>*</nowiki>''Citation of this Page'': “Myeloid proliferations associated with Down syndrome”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Myeloid_proliferations_associated_with_Down_syndrome</nowiki>.