HAEM5:B-lymphoblastic leukaemia/lymphoma with high hyperdiploidy - Revision history

Miguel.GonzalezMancera: /* Individual Region Genomic Gain/Loss/LOH */

2025-11-21T15:09:37Z

Individual Region Genomic Gain/Loss/LOH

← Older revision		Revision as of 10:09, 21 November 2025
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	==Individual Region Genomic Gain/Loss/LOH==		==Individual Region Genomic Gain/Loss/LOH==

	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.		* 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.
	{\| class="wikitable sortable"		{\| class="wikitable sortable"
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	==Genetic Diagnostic Testing Methods==		==Genetic Diagnostic Testing Methods==

	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>.		* 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>.

	==Familial Forms==		==Familial Forms==

Miguel.GonzalezMancera: /* Familial Forms */

2025-11-21T12:32:21Z

Familial Forms

← Older revision		Revision as of 07:32, 21 November 2025
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	==Familial Forms==		==Familial Forms==

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

Miguel.GonzalezMancera: /* Epigenomic Alterations */

2025-11-21T12:31:43Z

Epigenomic Alterations

← Older revision		Revision as of 07:31, 21 November 2025
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	==Epigenomic Alterations==		==Epigenomic Alterations==

	No relevant epigenomic alterations have been described.		No relevant epigenomic alterations have been described<ref name=":3" />.
	==Genes and Main Pathways Involved==		==Genes and Main Pathways Involved==
	{\| class="wikitable sortable"		{\| class="wikitable sortable"

Miguel.GonzalezMancera: /* Characteristic Chromosomal or Other Global Mutational Patterns */

2025-11-17T14:35:20Z

Characteristic Chromosomal or Other Global Mutational Patterns

← Older revision		Revision as of 09:35, 17 November 2025
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	\|Hyperdiploid		\|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" />.		\|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
	\|D: Needs demonstration of high-hyperdiploidy status (comprising 51–65 chromosomes) by karyotyping and/or FISH		\|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>.		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>.

Miguel.GonzalezMancera: /* Genetic Diagnostic Testing Methods */

2025-11-17T14:33:22Z

Genetic Diagnostic Testing Methods

← Older revision		Revision as of 09:33, 17 November 2025
Line 295:		Line 295:
	==Genetic Diagnostic Testing Methods==		==Genetic Diagnostic Testing Methods==

	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>.		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>.

	==Familial Forms==		==Familial Forms==

Miguel.GonzalezMancera: /* Gene Mutations (SNV/INDEL) */

2025-11-17T14:30:10Z

Gene Mutations (SNV/INDEL)

← Older revision		Revision as of 09:30, 17 November 2025
Line 209:		Line 209:

	<br />		<br />
	\|Nonsynonymous single nucleotide variant (SNV) in known codon 12 and 13 hotspot region, and additional mutations in codons 116 and 146<ref name=":5"~~>{{Cite journal\|last=Paulsson\|first=Kajsa\|last2=Johansson\|first2=Bertil\|date=2009-08\|title=High hyperdiploid childhood acute lymphoblastic leukemia\|url=https:~~/~~/pubmed.ncbi.nlm.nih.gov/19415723\|journal=Genes, Chromosomes & Cancer\|volume=48\|issue=8\|pages=637–660\|doi=10.1002/gcc.20671\|issn=1098-2264\|pmid=19415723}}</ref~~>		\|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		\|Oncogene
	\|Common		\|Common

Miguel.GonzalezMancera: /* Gene Mutations (SNV/INDEL) */

2025-11-17T14:22:05Z

Gene Mutations (SNV/INDEL)

← Older revision		Revision as of 09:22, 17 November 2025
Line 197:		Line 197:
	==Gene Mutations (SNV/INDEL)==		==Gene Mutations (SNV/INDEL)==

	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" /><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>.		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" />.
	{\| class="wikitable sortable"		{\| class="wikitable sortable"
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	==Genetic Diagnostic Testing Methods==		==Genetic Diagnostic Testing Methods==

	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" /> <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>.		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>.

	==Familial Forms==		==Familial Forms==

Miguel.GonzalezMancera: /* Gene Mutations (SNV/INDEL) */

2025-11-17T14:21:40Z

Gene Mutations (SNV/INDEL)

← Older revision		Revision as of 09:21, 17 November 2025
Line 197:		Line 197:
	==Gene Mutations (SNV/INDEL)==		==Gene Mutations (SNV/INDEL)==

	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=":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>.		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" /><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>.
	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-

Miguel.GonzalezMancera: /* Characteristic Chromosomal or Other Global Mutational Patterns */

2025-11-17T14:10:36Z

Characteristic Chromosomal or Other Global Mutational Patterns

← Older revision		Revision as of 09:10, 17 November 2025
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	==Individual Region Genomic Gain/Loss/LOH==		==Individual Region Genomic Gain/Loss/LOH==

	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" />. Below are the typical chromosomal gains described.		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.
	{\| class="wikitable sortable"		{\| class="wikitable sortable"
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	\|-		\|-
	\|Hyperdiploid		\|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<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~~>.		\|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		\|D: Needs demonstration of high-hyperdiploidy status (comprising 51–65 chromosomes) by karyotyping and/or FISH

Miguel.GonzalezMancera: /* Individual Region Genomic Gain/Loss/LOH */

2025-11-17T14:07:38Z

Individual Region Genomic Gain/Loss/LOH

← Older revision		Revision as of 09:07, 17 November 2025
Line 75:		Line 75:
	==Individual Region Genomic Gain/Loss/LOH==		==Individual Region Genomic Gain/Loss/LOH==

	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" />. Below are the typical chromosomal gains described.		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" />. Below are the typical chromosomal gains described.
	{\| class="wikitable sortable"		{\| class="wikitable sortable"
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	\|-		\|-
	\|Hyperdiploid		\|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<ref>{{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>.		\|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<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>.
	\|		\|
	\|D: Needs demonstration of high-hyperdiploidy status (comprising 51–65 chromosomes) by karyotyping and/or FISH		\|D: Needs demonstration of high-hyperdiploidy status (comprising 51–65 chromosomes) by karyotyping and/or FISH