HAEM5:B-lymphoblastic leukaemia/lymphoma with hypodiploidy: Difference between revisions

|Near-haploid B-ALL/LBL with hypodiploidy<ref>{{Cite journal|title=BlueBooksOnline|url=https://tumourclassification.iarc.who.int/chaptercontent/63/293}}</ref>

|24–31 chromosomes

|Associated with poor prognosis

|No

|This is a very rare category, has been observed in the pediatric population with virtually no adult cases reported.  Nonrandom retention of the X chromosome plus chromosomes 8, 14, 18, and 21 are frequently observed.

|Low-hypodiploid B-ALL/LBL with hypodiploidy

|No

|Low-hypodiploid B-ALL/LBL is rare in children (< 1%); however, the frequency increases with age, accounting for 5% of B-ALL/LBL cases in adolescents and young adults, and > 10% of cases in adults. Nonrandom retention of two copies of chromosomes from the following: the sex chromosomes plus chromosomes 1,6, 8, 10, 14, 18, and19.  Chromosome 21 is almost always retained in two copies.

|Associated with poor prognosis

|No

|Chromosome abnormalities include whole chromosome loss, specifically one sex chromosome and often chromosomes 7, 9, and/or 13.  Also detected are structural anomalies especially dicentric chromosomes involving chromosomes 7, 9 or 12.

'''Note: A slight variation in the range of chromosome number has been reported in the literature in the classification of NH, LH, HH and NH'''<ref name=":0" /><ref name=":1">{{Cite journal|last=Terwilliger|first=T.|last2=Abdul-Hay|first2=M.|date=2017|title=Acute lymphoblastic leukemia: a comprehensive review and 2017 update|url=https://www.ncbi.nlm.nih.gov/pubmed/28665419|journal=Blood Cancer Journal|volume=7|issue=6|pages=e577|doi=10.1038/bcj.2017.53|issn=2044-5385|pmc=5520400|pmid=28665419}}</ref><ref name=":2" /><ref name=":5" /><ref name=":3" /><ref>{{Cite journal|last=Safavi|first=Setareh|last2=Paulsson|first2=Kajsa|date=2017|title=Near-haploid and low-hypodiploid acute lymphoblastic leukemia: two distinct subtypes with consistently poor prognosis|url=https://www.ncbi.nlm.nih.gov/pubmed/27903530|journal=Blood|volume=129|issue=4|pages=420–423|doi=10.1182/blood-2016-10-743765|issn=1528-0020|pmid=27903530}}</ref><ref>{{Cite journal|last=Mehta|first=Parinda 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R.|last2=Mullighan|first2=C. G.|date=2010|title=Genomic profiling of high-risk acute lymphoblastic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/20739952|journal=Leukemia|volume=24|issue=10|pages=1676–1685|doi=10.1038/leu.2010.177|issn=1476-5551|pmid=20739952}}</ref><ref name=":4">Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD (2018). Acute lymphoblastic  leukemia (ALL). Medscape. emedicine, Medscape Article, Drugs & Diseases, Hematology.</ref>  '''[1-17].'''  

|''TP53''<br />

|The majority are missense mutations located in exon 7, exon 8, exon 6, and exon 5. Less frequent frameshift mutations in exon 4 and 7 have been described<ref name=":6" />. In general are predicted to be loss of function (LOF) mutations.

|Common  (>90%)

|Approximately 50% of children with low-hypodiploid B-ALL/LBL carry germline ''TP53'' variants associated with Li–Fraumeni syndrome, an autosomal dominant disorder caused by ''TP53'' mutations. These alterations correlate with low-hypodiploid ALL (32–39 chromosomes) and poorer clinical outcomes<ref name=":2" />.

|-

|''RB1''

|Associated with low-hypodiploid B-ALL.

|Associated with low-hypodiploid B-ALL.

|''IKZF3''  

|No

|Associated with near-haploid B-ALL.

|''NF1, NRAS, KRAS, MAPK1, FLT3 or PTPN11''; Activating mutations<ref name=":2" />

|RTK or Ras signaling

|Constitutive activation of mitogenic and anti-apoptotic pathways, driving uncontrolled cell proliferation, survival, and malignant transformation