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

* This entity is defined by a hyperdiploid pattern with a karyotype comprising 51–65 chromosomes with recurrent, non-random gains of one or more copies of entire chromosomes<ref name=":3" />.

* Highly homogeneous genomes are seen for most of the leukemias, with predominantly whole chromosome gains being present in all cells<ref name=":6">{{Cite journal|last=Woodward|first=Eleanor L.|last2=Yang|first2=Minjun|last3=Moura-Castro|first3=Larissa H.|last4=van den Bos|first4=Hilda|last5=Gunnarsson|first5=Rebeqa|last6=Olsson-Arvidsson|first6=Linda|last7=Spierings|first7=Diana C. J.|last8=Castor|first8=Anders|last9=Duployez|first9=Nicolas|date=2023-03-25|title=Clonal origin and development of high hyperdiploidy in childhood acute lymphoblastic leukaemia|url=https://pubmed.ncbi.nlm.nih.gov/36966135|journal=Nature Communications|volume=14|issue=1|pages=1658|doi=10.1038/s41467-023-37356-5|issn=2041-1723|pmc=10039905|pmid=36966135}}</ref>. Below are the typical chromosomal gains described.

|No (NCCN)

|No (NCCN)

|No (NCCN)

|No (NCCN)

|No (NCCN)

|No (NCCN)

|''See "prognostic significance" section for +4 above''

|No (NCCN)

|''See prognostic significance" section for +4 above''

|No (NCCN)

|No (NCCN)

|N/A

|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" />.

|Ubiquitous

Nine genes have been found to be recurrently mutated and were also either mutated more frequently than expected by chance or targeted by structural events<ref name=":2" />.

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

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

No relevant epigenomic alterations have been described<ref name=":3" />.  

* 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" />.  

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