HAEM5:B-lymphoblastic leukaemia/lymphoma with hypodiploidy: Difference between revisions
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|Low-hypodiploid B-ALL/LBL with hypodiploidy (32–39 chromosomes) | |Low-hypodiploid B-ALL/LBL with hypodiploidy (32–39 chromosomes) | ||
|More than 90% of low-hypodiploid patients have been identified with ''TP53'' mutations, which occur in virtually all low-hypodiploid B-ALL cases due to the very recurrent loss of chromosome 17<ref name=":6" /><ref name=":9" /><ref>{{Cite journal|last=Stengel|first=Anna|last2=Schnittger|first2=Susanne|last3=Weissmann|first3=Sandra|last4=Kuznia|first4=Sabrina|last5=Kern|first5=Wolfgang|last6=Kohlmann|first6=Alexander|last7=Haferlach|first7=Torsten|last8=Haferlach|first8=Claudia|date=2014-07-10|title=TP53 mutations occur in 15.7% of ALL and are associated with MYC-rearrangement, low hypodiploidy, and a poor prognosis|url=https://pubmed.ncbi.nlm.nih.gov/24829203|journal=Blood|volume=124|issue=2|pages=251–258|doi=10.1182/blood-2014-02-558833|issn=1528-0020|pmid=24829203}}</ref>. p53 is one of the most prominent tumor suppressors. Its activation as a transcription factor stimulates downstream pathways leading to protective cellular processes, including cell-cycle arrest, apoptosis, and senescence, to prevent the propagation of genetically altered cells<ref>{{Cite journal|last=Vogelstein|first=B.|last2=Lane|first2=D.|last3=Levine|first3=A. J.|date=2000-11-16|title=Surfing the p53 network|url=https://pubmed.ncbi.nlm.nih.gov/11099028|journal=Nature|volume=408|issue=6810|pages=307–310|doi=10.1038/35042675|issn=0028-0836|pmid=11099028}}</ref>. | |More than 90% of low-hypodiploid patients have been identified with ''TP53'' mutations, which occur in virtually all low-hypodiploid B-ALL cases due to the very recurrent loss of chromosome 17<ref name=":6" /><ref name=":9" /><ref name=":10">{{Cite journal|last=Stengel|first=Anna|last2=Schnittger|first2=Susanne|last3=Weissmann|first3=Sandra|last4=Kuznia|first4=Sabrina|last5=Kern|first5=Wolfgang|last6=Kohlmann|first6=Alexander|last7=Haferlach|first7=Torsten|last8=Haferlach|first8=Claudia|date=2014-07-10|title=TP53 mutations occur in 15.7% of ALL and are associated with MYC-rearrangement, low hypodiploidy, and a poor prognosis|url=https://pubmed.ncbi.nlm.nih.gov/24829203|journal=Blood|volume=124|issue=2|pages=251–258|doi=10.1182/blood-2014-02-558833|issn=1528-0020|pmid=24829203}}</ref>. p53 is one of the most prominent tumor suppressors. Its activation as a transcription factor stimulates downstream pathways leading to protective cellular processes, including cell-cycle arrest, apoptosis, and senescence, to prevent the propagation of genetically altered cells<ref>{{Cite journal|last=Vogelstein|first=B.|last2=Lane|first2=D.|last3=Levine|first3=A. J.|date=2000-11-16|title=Surfing the p53 network|url=https://pubmed.ncbi.nlm.nih.gov/11099028|journal=Nature|volume=408|issue=6810|pages=307–310|doi=10.1038/35042675|issn=0028-0836|pmid=11099028}}</ref>. | ||
|Rare in children, recurrent in adolescents, young adults, and adults | |Rare in children, recurrent in adolescents, young adults, and adults | ||
|P: Associated with poor prognosis. EFS 30–50%<ref name=":8" />. | |P: Associated with poor prognosis. EFS 30–50%<ref name=":8" />. | ||
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==Familial Forms== | ==Familial Forms== | ||
In Low hypodiploid (LH), several studies have not only identified a high percentage of pediatric patients with ''TP53'' mutations, but close to half displayed germline mutations, suggesting that LH ALL is a manifestation of Li-Fraumeni syndrome in children. | In Low hypodiploid (LH), several studies have not only identified a high percentage of pediatric patients with ''TP53'' mutations, but close to half displayed germline mutations, suggesting that LH ALL is a manifestation of Li-Fraumeni syndrome in children<ref name=":2" /><ref name=":10" /><ref>{{Cite journal|last=Comeaux|first=Evan Q.|last2=Mullighan|first2=Charles G.|date=2017-03-01|title=TP53 Mutations in Hypodiploid Acute Lymphoblastic Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/28003275|journal=Cold Spring Harbor Perspectives in Medicine|volume=7|issue=3|pages=a026286|doi=10.1101/cshperspect.a026286|issn=2157-1422|pmc=5334249|pmid=28003275}}</ref>. | ||
Adults also showed a high incidence of ''TP53'' mutations, but these mutations appear to be somatic in origin. In NH, mutations of genes of receptor tyrosine kinase (RTK) pathway, Ras signaling, ''IKZF3'' (17q21.1) and histone clusters, but mutations of ''IZFK2'', ''RB1'', or ''TP53'' were rare. | Adults also showed a high incidence of ''TP53'' mutations, but these mutations appear to be somatic in origin. In NH, mutations of genes of receptor tyrosine kinase (RTK) pathway, Ras signaling, ''IKZF3'' (17q21.1) and histone clusters, but mutations of ''IZFK2'', ''RB1'', or ''TP53'' were rare. | ||