HAEM5:Acute myeloid leukaemia with RUNX1::RUNX1T1 fusion: Difference between revisions
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<blockquote class= | <blockquote class='blockedit'>{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Acute Myeloid Leukemia (AML) with t(8;21)(q22;q22.1); RUNX1-RUNX1T1]]. | ||
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<blockquote class= | <blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}</blockquote> | ||
*May present as a myeloid sarcoma and, if so, the bone marrow aspirate blast count may be misleadingly low | *May present as a myeloid sarcoma and, if so, the bone marrow aspirate blast count may be misleadingly low | ||
*Concurrent systemic mastocytosis has been reported. | *Concurrent systemic mastocytosis has been reported. | ||
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==Sites of Involvement== | ==Sites of Involvement== | ||
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<blockquote class= | <blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote> | ||
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<blockquote class= | <blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in: | ||
* Chromosomal Rearrangements (Gene Fusions) | * Chromosomal Rearrangements (Gene Fusions) | ||
* Individual Region Genomic Gain/Loss/LOH | * Individual Region Genomic Gain/Loss/LOH | ||
* Characteristic Chromosomal Patterns | * Characteristic Chromosomal Patterns | ||
* Gene Mutations (SNV/INDEL)}} | * Gene Mutations (SNV/INDEL)}}</blockquote> | ||
Diagnostic: | Diagnostic: | ||
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*Recently homoharringtonine, aclarubicin and cytarabine as the first course of induction therapy has been found to be highly effective for acute myeloid leukemia with t(8;21)(q22;q22)<ref name=":0" />. | *Recently homoharringtonine, aclarubicin and cytarabine as the first course of induction therapy has been found to be highly effective for acute myeloid leukemia with t(8;21)(q22;q22)<ref name=":0" />. | ||
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==Individual Region Genomic Gain / Loss / LOH== | ==Individual Region Genomic Gain / Loss / LOH== | ||
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9q22 loss | 9q22 loss | ||
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==Characteristic Chromosomal Patterns== | ==Characteristic Chromosomal Patterns== | ||
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<blockquote class= | <blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}</blockquote> | ||
Additional aberrations in >70% of cases with t(8;21); common loss of a sex chromosome or deletion 9q | Additional aberrations in >70% of cases with t(8;21); common loss of a sex chromosome or deletion 9q | ||
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Trisomy 4 is a rare numerical abnormality detected in 3% of AML patients with t(8;21) (PMIDs: 12682630, 26573082, 27451976). A negative effect on prognosis this group of patients has been attributed to the presence of the mutations in the KIT gene.. Gain of chromosome 4 would likely result in increased dosage of the mutant KIT allele (PMIDs: 16291592, 30899636). | Trisomy 4 is a rare numerical abnormality detected in 3% of AML patients with t(8;21) (PMIDs: 12682630, 26573082, 27451976). A negative effect on prognosis this group of patients has been attributed to the presence of the mutations in the KIT gene.. Gain of chromosome 4 would likely result in increased dosage of the mutant KIT allele (PMIDs: 16291592, 30899636). | ||
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==Gene Mutations (SNV / INDEL)== | ==Gene Mutations (SNV / INDEL)== | ||
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AML with t(8;21)(q22;q22) has genetic heterogeneity at the molecular level. Several genes have been identified that are frequently mutated in this subset of AML, some of them adversely affecting prognosis. | AML with t(8;21)(q22;q22) has genetic heterogeneity at the molecular level. Several genes have been identified that are frequently mutated in this subset of AML, some of them adversely affecting prognosis. | ||
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==Epigenomic Alterations== | ==Epigenomic Alterations== | ||
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<blockquote class= | <blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote> | ||
Genes: | Genes: | ||
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*The normal transcriptional activity of the RUNX1 protein in the core binding factor is affected in a negative manner by the chimeric protein encoded by the RUNX1-RUNX1T1 fusion gene. It has been proposed that the RUNX1-RUNX1T1 protein recruits histone deacetylases and DNA methyl transferase 1 to core binding factor target genes<ref>{{Cite journal|last=Marcucci|first=Guido|date=2006|title=Core binding factor acute myeloid leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/16728942|journal=Clinical Advances in Hematology & Oncology: H&O|volume=4|issue=5|pages=339–341|issn=1543-0790|pmid=16728942}}</ref>. This leads to increased chromatin deacetylation and promotor hypermethylation, resulting in gene transcriptional repression and disruption of normal cellular pathways of hematopoiesis. | *The normal transcriptional activity of the RUNX1 protein in the core binding factor is affected in a negative manner by the chimeric protein encoded by the RUNX1-RUNX1T1 fusion gene. It has been proposed that the RUNX1-RUNX1T1 protein recruits histone deacetylases and DNA methyl transferase 1 to core binding factor target genes<ref>{{Cite journal|last=Marcucci|first=Guido|date=2006|title=Core binding factor acute myeloid leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/16728942|journal=Clinical Advances in Hematology & Oncology: H&O|volume=4|issue=5|pages=339–341|issn=1543-0790|pmid=16728942}}</ref>. This leads to increased chromatin deacetylation and promotor hypermethylation, resulting in gene transcriptional repression and disruption of normal cellular pathways of hematopoiesis. | ||
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==Genetic Diagnostic Testing Methods== | ==Genetic Diagnostic Testing Methods== | ||