HAEM5:Acute myeloid leukaemia with NPM1 mutation: Difference between revisions

<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 Mutated NPM1]].

 

 

==Definition / Description of Disease==

 

 

==Synonyms / Terminology==

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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*Mutated ''NPM1'' is associated with a favorable prognosis in AML patients who do not have FLT3-internal tandem duplication (FLT3-ITD) mutations and with normal karyotype<ref name=":0" /><ref name=":1" /><ref>{{Cite journal|last=Schnittger|first=S.|last2=Bacher|first2=U.|last3=Kern|first3=W.|last4=Alpermann|first4=T.|last5=Haferlach|first5=C.|last6=Haferlach|first6=T.|date=2011|title=Prognostic impact of FLT3-ITD load in NPM1 mutated acute myeloid leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/21537333|journal=Leukemia|volume=25|issue=8|pages=1297–1304|doi=10.1038/leu.2011.97|issn=1476-5551|pmid=21537333}}</ref><ref name=":7">{{Cite journal|last=Schnittger|first=Susanne|last2=Kern|first2=Wolfgang|last3=Tschulik|first3=Claudia|last4=Weiss|first4=Tamara|last5=Dicker|first5=Frank|last6=Falini|first6=Brunangelo|last7=Haferlach|first7=Claudia|last8=Haferlach|first8=Torsten|date=2009|title=Minimal residual disease levels assessed by NPM1 mutation-specific RQ-PCR provide important prognostic information in AML|url=https://www.ncbi.nlm.nih.gov/pubmed/19587375|journal=Blood|volume=114|issue=11|pages=2220–2231|doi=10.1182/blood-2009-03-213389|issn=1528-0020|pmid=19587375}}</ref>. A more recent study found that ''NPM1''-positive/''FLT3''-ITD-negative genotype predicts favorable outcomes in AML patients younger than 65 years, but not in those older than 65 years<ref>{{Cite journal|last=Ostronoff|first=Fabiana|last2=Othus|first2=Megan|last3=Lazenby|first3=Michelle|last4=Estey|first4=Elihu|last5=Appelbaum|first5=Frederick R.|last6=Evans|first6=Anna|last7=Godwin|first7=John|last8=Gilkes|first8=Amanda|last9=Kopecky|first9=Kenneth J.|date=2015|title=Prognostic significance of NPM1 mutations in the absence of FLT3-internal tandem duplication in older patients with acute myeloid leukemia: a SWOG and UK National Cancer Research Institute/Medical Research Council report|url=https://www.ncbi.nlm.nih.gov/pubmed/25713434|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=33|issue=10|pages=1157–1164|doi=10.1200/JCO.2014.58.0571|issn=1527-7755|pmc=4372852|pmid=25713434}}</ref>. Besides ''FLT3''-ITD, the prognostic impact of ''NPM1'' mutations in AML can be modified by the presence of other concurrent mutations. In ''NPM1'' mutated AML, concurrent mutations have been found in ''DNMT3A'' (54%), ''NRAS'' (19%), ''TET2'' (16%) and ''PTPN11'' (15%)<ref name=":1" />. ''DNMT3A'' missense mutations predicted shorter overall survival and higher cumulative incidence of relapse when stratified by ''NPM1'' mutation status, whereas '''NRAS'' truncation mutations do not correlate with clinical outcome<ref>{{Cite journal|last=Gale|first=Rosemary E.|last2=Lamb|first2=Katarina|last3=Allen|first3=Christopher|last4=El-Sharkawi|first4=Dima|last5=Stowe|first5=Cassandra|last6=Jenkinson|first6=Sarah|last7=Tinsley|first7=Steven|last8=Dickson|first8=Glenda|last9=Burnett|first9=Alan K.|date=2015|title=Simpson's Paradox and the Impact of Different DNMT3A Mutations on Outcome in Younger Adults With Acute Myeloid Leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/25964253|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=33|issue=18|pages=2072–2083|doi=10.1200/JCO.2014.59.2022|issn=1527-7755|pmid=25964253}}</ref>. ''NRAS'' codon Gly12 and Gly13 mutations predict better overall survival in AML patients with concurrent ''NPM1'' and ''DNMT3A'' mutations<ref name=":1" />.

!Chr #!!'''Gain, Loss, Amp, LOH'''!!'''Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]'''!!'''Relevant Gene(s)'''

!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''

!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''

!'''Clinical Relevance Details/Other Notes'''

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!'''Prevalence -'''

'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''

!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''

!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''

!'''Clinical Relevance Details/Other Notes'''

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!Gene!!'''Genetic Alteration'''!!'''Tumor Suppressor Gene, Oncogene, Other'''!!'''Prevalence -'''

'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''

!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  '''

!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''

!'''Clinical Relevance Details/Other Notes'''

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[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases A]]