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

 

[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]

<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:B-Lymphoblastic Leukemia/Lymphoma with Hyperdiploidy]].

<span style="color:#0070C0">(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)</span>

Miguel Gonzalez Mancera, MD

{| class="wikitable"

|-

|Haematolymphoid Tumours (5th ed.)

|B-cell lymphoid proliferations and lymphomas

|-

|Family

|Precursor B-cell neoplasms

|-

|Type

|B-lymphoblastic leukaemias/lymphomas

|-

|Subtype(s)

|B-lymphoblastic leukaemia/lymphoma with high hyperdiploidy

|}

|+

|Acceptable

| ||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||

|

|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.

|

<blockquote class="blockedit">

==Individual Region Genomic Gain/Loss/LOH==

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

|21

|No (NCCN)

|Chromosome 21 is universally gained in high-hyperdiploid B-ALL/LBL <ref>{{Cite journal|last=Harrison|first=Christine J.|last2=Haas|first2=Oskar|last3=Harbott|first3=Jochen|last4=Biondi|first4=Andrea|last5=Stanulla|first5=Martin|last6=Trka|first6=Jan|last7=Izraeli|first7=Shai|last8=Biology and Diagnosis Committee of International Berlin-Frankfürt-Münster study group|date=2010-10|title=Detection of prognostically relevant genetic abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: recommendations from the Biology and Diagnosis Committee of the International Berlin-Frankfürt-Münster study group|url=https://pubmed.ncbi.nlm.nih.gov/20701601|journal=British Journal of Haematology|volume=151|issue=2|pages=132–142|doi=10.1111/j.1365-2141.2010.08314.x|issn=1365-2141|pmid=20701601}}</ref>; therefore, the presence of multiple (three to five) discrete ''RUNX1'' signals seen when using ''ETV6''::''RUNX1'' FISH probes suggests the presence of high hyperdiploidy.

|X

|No (NCCN)

|N/A

|6

|No (NCCN)

|N/A

|14

|No (NCCN)

|The prognostic impact of the “triple trisomies”, i.e., concurrent rent +4, +10, and +17, is debated; they have been reported to be associated with low risk by the Children’s Oncology Group (COG)<ref>{{Cite journal|last=Schultz|first=Kirk R.|last2=Pullen|first2=D. Jeanette|last3=Sather|first3=Harland N.|last4=Shuster|first4=Jonathan J.|last5=Devidas|first5=Meenakshi|last6=Borowitz|first6=Michael J.|last7=Carroll|first7=Andrew J.|last8=Heerema|first8=Nyla A.|last9=Rubnitz|first9=Jeffrey E.|date=2007-02-01|title=Risk- and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children's Cancer Group (CCG)|url=https://pubmed.ncbi.nlm.nih.gov/17003380|journal=Blood|volume=109|issue=3|pages=926–935|doi=10.1182/blood-2006-01-024729|issn=0006-4971|pmc=1785141|pmid=17003380}}</ref>, but not in UK trials<ref name=":1" />.

|N/A

<blockquote class="blockedit"></blockquote><blockquote class="blockedit">

==Characteristic Chromosomal or Other Global Mutational Patterns==

!Chromosomal Pattern

!Molecular Pathogenesis

!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

|Hyperdiploid

|Although pathogenetic mechanisms are poorly understood, chromosomal gains are early events in the pathogenesis, possibly already before birth, and are the main driver<ref name=":3">WHO Classification of Tumours: Haematolymphoid Tumours [Internet; Beta Version Ahead of Print](5th ed.), International Agency for Research on Cancer (2022)</ref><ref>{{Cite journal|last=Szczepański|first=T.|last2=Willemse|first2=M. J.|last3=van Wering|first3=E. R.|last4=van Weerden|first4=J. F.|last5=Kamps|first5=W. A.|last6=van Dongen|first6=J. J.|date=2001-09|title=Precursor-B-ALL with D(H)-J(H) gene rearrangements have an immature immunogenotype with a high frequency of oligoclonality and hyperdiploidy of chromosome 14|url=https://pubmed.ncbi.nlm.nih.gov/11516102|journal=Leukemia|volume=15|issue=9|pages=1415–1423|doi=10.1038/sj.leu.2402206|issn=0887-6924|pmid=11516102}}</ref><ref>{{Cite journal|last=Maia|first=A. T.|last2=van der Velden|first2=V. H. J.|last3=Harrison|first3=C. J.|last4=Szczepanski|first4=T.|last5=Williams|first5=M. D.|last6=Griffiths|first6=M. J.|last7=van Dongen|first7=J. J. M.|last8=Greaves|first8=M. F.|date=2003-11|title=Prenatal origin of hyperdiploid acute lymphoblastic leukemia in identical twins|url=https://pubmed.ncbi.nlm.nih.gov/12931229|journal=Leukemia|volume=17|issue=11|pages=2202–2206|doi=10.1038/sj.leu.2403101|issn=0887-6924|pmid=12931229}}</ref><ref>{{Cite journal|last=Maia|first=Ana Teresa|last2=Tussiwand|first2=Roxane|last3=Cazzaniga|first3=Giovanni|last4=Rebulla|first4=Paolo|last5=Colman|first5=Susan|last6=Biondi|first6=Andrea|last7=Greaves|first7=Mel|date=2004-05|title=Identification of preleukemic precursors of hyperdiploid acute lymphoblastic leukemia in cord blood|url=https://pubmed.ncbi.nlm.nih.gov/15034866|journal=Genes, Chromosomes & Cancer|volume=40|issue=1|pages=38–43|doi=10.1002/gcc.20010|issn=1045-2257|pmid=15034866}}</ref><ref name=":2" />. It was suggested that the aneuploidy in these cases likely arises by an initial tripolar mitosis in a diploid cell followed by clonal evolution. During the clonal evolution, chromosomes that changed in copy number comprised X, 8, 9, 14, 16, 17, and 21<ref name=":6" />.

|D: Needs demonstration of high-hyperdiploidy status (comprising 51–65 chromosomes) by karyotyping and/or FISH

P: B-ALL/LBL with high-hyperdiploidy has a very favorable prognosis, with long-term overall survival in > 90% of children<ref name=":0">{{Cite journal|last=Paulsson|first=Kajsa|last2=Forestier|first2=Erik|last3=Andersen|first3=Mette K.|last4=Autio|first4=Kirsi|last5=Barbany|first5=Gisela|last6=Borgström|first6=Georg|last7=Cavelier|first7=Lucia|last8=Golovleva|first8=Irina|last9=Heim|first9=Sverre|date=2013-09|title=High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols|url=https://pubmed.ncbi.nlm.nih.gov/23645689|journal=Haematologica|volume=98|issue=9|pages=1424–1432|doi=10.3324/haematol.2013.085852|issn=1592-8721|pmc=3762100|pmid=23645689}}</ref>.

|No (NCCN)

|High event-free survival (EFS) was associated with trisomy 4, 6, 17, 18, and 22, presence of triple trisomies (4, 10, 17), and high modal numbers ( > 50 chromosomes)<ref name=":0" />.  

<blockquote class="blockedit"></blockquote>

*

==Gene Mutations (SNV/INDEL)==

!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

|''KRAS''

|Nonsynonymous single nucleotide variant (SNV) in known codon 12 and 13 hotspot region, and additional mutations in codons 116 and 146<ref name=":2" />

|Oncogene

|Common

|No

|''KRAS'' codons 117 and 146 may be new recurrent mutational hotspots in high hyperdiploid ALL<ref name=":2" />.

|''NRAS''

|Oncogene

|Recurrent

|No

|N/A

|N/A

|''CREBBP''

|''CREBBP'' has been reported to be mutated in a high proportion of relapsing high hyperdiploid childhood ALLs<ref>{{Cite journal|last=Inthal|first=A.|last2=Zeitlhofer|first2=P.|last3=Zeginigg|first3=M.|last4=Morak|first4=M.|last5=Grausenburger|first5=R.|last6=Fronkova|first6=E.|last7=Fahrner|first7=B.|last8=Mann|first8=G.|last9=Haas|first9=O. A.|date=2012-08|title=CREBBP HAT domain mutations prevail in relapse cases of high hyperdiploid childhood acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/22388726|journal=Leukemia|volume=26|issue=8|pages=1797–1803|doi=10.1038/leu.2012.60|issn=1476-5551|pmc=4194312|pmid=22388726}}</ref>.

|''WHSC1''

|Nonsynonymous SNV

|Histone methyltransferase

|Recurrent

|No

|No

|N/A

|No

|No

|''SETD2''

|Rare

|N/A

|''EZH2''

|Nonsynonymous SNV

|Histone methyltransferase

|Rarre

|No

|No

|N/A

|}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.

|''FLT3, NRAS, KRAS'' and ''PTPN11''<ref name=":2">{{Cite journal|last=Paulsson|first=Kajsa|last2=Lilljebjörn|first2=Henrik|last3=Biloglav|first3=Andrea|last4=Olsson|first4=Linda|last5=Rissler|first5=Marianne|last6=Castor|first6=Anders|last7=Barbany|first7=Gisela|last8=Fogelstrand|first8=Linda|last9=Nordgren|first9=Ann|date=2015-06|title=The genomic landscape of high hyperdiploid childhood acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/25961940|journal=Nature Genetics|volume=47|issue=6|pages=672–676|doi=10.1038/ng.3301|issn=1546-1718|pmid=25961940}}</ref>; Activating mutations

|Receptor tyrosine kinase (RTK)-RAS signaling

|Increased proliferation, differentiation, and survival

* Hyperdiploidy is readily identifiable by conventional chromosome studies, FISH and CMA.  

* CMA studies have shown that approximately 80% of hyperdiploid cases have additional genomic abnormalities with chromosomes commonly involved being 1, 9, 11, 12, and X<ref name=":4">{{Cite journal|last=Paulsson|first=Kajsa|last2=Forestier|first2=Erik|last3=Lilljebjörn|first3=Henrik|last4=Heldrup|first4=Jesper|last5=Behrendtz|first5=Mikael|last6=Young|first6=Bryan D.|last7=Johansson|first7=Bertil|date=2010-12-14|title=Genetic landscape of high hyperdiploid childhood acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/21098271|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=107|issue=50|pages=21719–21724|doi=10.1073/pnas.1006981107|issn=1091-6490|pmc=3003126|pmid=21098271}}</ref><ref>{{Cite journal|last=Schraders|first=Margit|last2=van Reijmersdal|first2=Simon V.|last3=Kamping|first3=Eveline J.|last4=van Krieken|first4=Johan H. J. M.|last5=van Kessel|first5=Ad Geurts|last6=Groenen|first6=Patricia J. T. A.|last7=Hoogerbrugge|first7=Peter M.|last8=Kuiper|first8=Roland P.|date=2009-05|title=High-resolution genomic profiling of pediatric lymphoblastic lymphomas reveals subtle differences with pediatric acute lymphoblastic leukemias in the B-lineage|url=https://pubmed.ncbi.nlm.nih.gov/19389505|journal=Cancer Genetics and Cytogenetics|volume=191|issue=1|pages=27–33|doi=10.1016/j.cancergencyto.2009.01.002|issn=1873-4456|pmid=19389505}}</ref><ref>{{Cite journal|last=Steeghs|first=Elisabeth M. P.|last2=Boer|first2=Judith M.|last3=Hoogkamer|first3=Alex Q.|last4=Boeree|first4=Aurélie|last5=de Haas|first5=Valerie|last6=de Groot-Kruseman|first6=Hester A.|last7=Horstmann|first7=Martin A.|last8=Escherich|first8=Gabriele|last9=Pieters|first9=Rob|date=03 15, 2019|title=Copy number alterations in B-cell development genes, drug resistance, and clinical outcome in pediatric B-cell precursor acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/30874617|journal=Scientific Reports|volume=9|issue=1|pages=4634|doi=10.1038/s41598-019-41078-4|issn=2045-2322|pmc=6420659|pmid=30874617}}</ref><ref>{{Cite journal|last=Lejman|first=Monika|last2=Zawitkowska|first2=Joanna|last3=Styka|first3=Borys|last4=Babicz|first4=Mariusz|last5=Winnicka|first5=Dorota|last6=Zaucha-Prażmo|first6=Agnieszka|last7=Pastorczak|first7=Agata|last8=Taha|first8=Joanna|last9=Młynarski|first9=Wojciech|date=08 2019|title=Microarray testing as an efficient tool to redefine hyperdiploid paediatric B-cell precursor acute lymphoblastic leukaemia patients|url=https://pubmed.ncbi.nlm.nih.gov/31202078|journal=Leukemia Research|volume=83|pages=106163|doi=10.1016/j.leukres.2019.05.013|issn=1873-5835|pmid=31202078}}</ref>.

No familial forms have been described<ref name=":3" />.  

<references />

[[Category:HAEM5]]

[[Category:DISEASE]]

[[Category:Diseases B]]