HAEM5:B-lymphoblastic leukaemia/lymphoma with hypodiploidy - Revision history

Miguel.GonzalezMancera: /* Genes and Main Pathways Involved */

2025-11-21T15:28:28Z

Genes and Main Pathways Involved

← Older revision		Revision as of 10:28, 21 November 2025
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	\|Propagation of genetically altered cells.		\|Propagation of genetically altered cells.
	\|-		\|-
	\|''IKZF1, IKZF2, IKZF3, PAX5, EBF1, VPREB1''		\|''IKZF1, IKZF2, IKZF3, PAX5, EBF1, VPREB1''<ref name=":16" />
	\|B-cell development		\|B-cell development
	\|Altered lymphoid development and differentiation.		\|Altered lymphoid development and differentiation.
	\|-		\|-
	\|''PAG1''		\|''PAG1<ref name=":16" />''
	\|BCR signaling		\|BCR signaling
	\|Altered regulatory function in proximal B cell–receptor signaling.		\|Altered regulatory function in proximal B cell–receptor signaling.
	\|-		\|-
	\|''ETV6''		\|''ETV6<ref name=":16" />''
	\|Hematopoiesis		\|Hematopoiesis
	\|Not fully elucidated in this entity		\|Not fully elucidated in this entity
	\|-		\|-
	\|''ARPP21''		\|''ARPP21<ref name=":16" />''
	\|Calmodulin signaling		\|Calmodulin signaling
	\|Not fully elucidated in this entity		\|Not fully elucidated in this entity
	\|-		\|-
	\|''SLX4IP''		\|''SLX4IP<ref name=":16" />''
	\|Telomere length maintenance		\|Telomere length maintenance
	\|Not fully elucidated in this entity		\|Not fully elucidated in this entity
	\|-		\|-
	\|''CUL5''		\|''CUL5<ref name=":16" />''
	\|Ubiquitin pathway		\|Ubiquitin pathway
	\|Not fully elucidated in this entity		\|Not fully elucidated in this entity
	\|-		\|-
	\|''FAM53B''		\|''FAM53B<ref name=":16" />''
	\|Wnt signaling		\|Wnt signaling
	\|Not fully elucidated in this entity		\|Not fully elucidated in this entity
	\|-		\|-
	\|''PDS5B''		\|''PDS5B<ref name=":16" />''
	\|Cohesis complex		\|Cohesis complex
	\|Not fully elucidated in this entity		\|Not fully elucidated in this entity
	\|-		\|-
	\|''ANKRD11, DMD''		\|''ANKRD11, DMD<ref name=":16" />''
	\|Cell adhesion		\|Cell adhesion
	\|Not fully elucidated in this entity		\|Not fully elucidated in this entity

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

2025-11-21T13:32:22Z

Characteristic Chromosomal or Other Global Mutational Patterns

← Older revision		Revision as of 08:32, 21 November 2025
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	</blockquote>		</blockquote>
	==Characteristic Chromosomal or Other Global Mutational Patterns==		==Characteristic Chromosomal or Other Global Mutational Patterns==
	This entity is defined by the presence of neoplastic lymphoblasts containing less than 46 chromosomes<ref name=":0">Borowitz MJ, et al., (2017). B-Lymphoblastic leukaemia/lymphoma with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p206.</ref>, and can be subdivided into near-haploid B-ALL/LBL with hypodiploidy (24–31 chromosomes); low-hypodiploid B-ALL/LBL with hypodiploidy (32–39 chromosomes); and high-hypodiploid B-ALL/LBL with hypodiploidy (40–43 chromosomes)<ref name=":13" /><ref name=":18">{{Cite journal\|last=Harrison\|first=Christine J.\|last2=Moorman\|first2=Anthony V.\|last3=Broadfield\|first3=Zoë J.\|last4=Cheung\|first4=Kan L.\|last5=Harris\|first5=Rachel L.\|last6=Reza Jalali\|first6=G.\|last7=Robinson\|first7=Hazel M.\|last8=Barber\|first8=Kerry E.\|last9=Richards\|first9=Sue M.\|date=2004\|title=Three distinct subgroups of hypodiploidy in acute lymphoblastic leukaemia\|url=https://www.ncbi.nlm.nih.gov/pubmed/15147369\|journal=British Journal of Haematology\|volume=125\|issue=5\|pages=552–559\|doi=10.1111/j.1365-2141.2004.04948.x\|issn=0007-1048\|pmid=15147369}}</ref>. Of note, near-diploid cases (44–45 chromosomes) are not included in the hypodiploid category in clinical therapy–directed classification schemes because they do not share the poor prognosis observed<ref name=":14" />. In a study, for patients with 44 chromosomes, monosomy 7, the presence of a dicentric chromosome, or both predicted a worse event-free survival (EFS) but similar overall survival (OS)<ref name=":3">{{Cite journal\|last=Nachman\|first=James B.\|last2=Heerema\|first2=Nyla A.\|last3=Sather\|first3=Harland\|last4=Camitta\|first4=Bruce\|last5=Forestier\|first5=Erik\|last6=Harrison\|first6=Christine J.\|last7=Dastugue\|first7=Nicole\|last8=Schrappe\|first8=Martin\|last9=Pui\|first9=Ching-Hon\|date=2007\|title=Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia\|url=https://www.ncbi.nlm.nih.gov/pubmed/17473063\|journal=Blood\|volume=110\|issue=4\|pages=1112–1115\|doi=10.1182/blood-2006-07-038299\|issn=0006-4971\|pmc=1939895\|pmid=17473063}}</ref>.		This entity is defined by the presence of neoplastic lymphoblasts containing less than 46 chromosomes, and can be subdivided into near-haploid B-ALL/LBL with hypodiploidy (24–31 chromosomes); low-hypodiploid B-ALL/LBL with hypodiploidy (32–39 chromosomes); and high-hypodiploid B-ALL/LBL with hypodiploidy (40–43 chromosomes)<ref name=":13" /><ref name=":18">{{Cite journal\|last=Harrison\|first=Christine J.\|last2=Moorman\|first2=Anthony V.\|last3=Broadfield\|first3=Zoë J.\|last4=Cheung\|first4=Kan L.\|last5=Harris\|first5=Rachel L.\|last6=Reza Jalali\|first6=G.\|last7=Robinson\|first7=Hazel M.\|last8=Barber\|first8=Kerry E.\|last9=Richards\|first9=Sue M.\|date=2004\|title=Three distinct subgroups of hypodiploidy in acute lymphoblastic leukaemia\|url=https://www.ncbi.nlm.nih.gov/pubmed/15147369\|journal=British Journal of Haematology\|volume=125\|issue=5\|pages=552–559\|doi=10.1111/j.1365-2141.2004.04948.x\|issn=0007-1048\|pmid=15147369}}</ref>. Of note, near-diploid cases (44–45 chromosomes) are not included in the hypodiploid category in clinical therapy–directed classification schemes because they do not share the poor prognosis observed<ref name=":14" />. In a study, for patients with 44 chromosomes, monosomy 7, the presence of a dicentric chromosome, or both predicted a worse event-free survival (EFS) but similar overall survival (OS)<ref name=":3">{{Cite journal\|last=Nachman\|first=James B.\|last2=Heerema\|first2=Nyla A.\|last3=Sather\|first3=Harland\|last4=Camitta\|first4=Bruce\|last5=Forestier\|first5=Erik\|last6=Harrison\|first6=Christine J.\|last7=Dastugue\|first7=Nicole\|last8=Schrappe\|first8=Martin\|last9=Pui\|first9=Ching-Hon\|date=2007\|title=Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia\|url=https://www.ncbi.nlm.nih.gov/pubmed/17473063\|journal=Blood\|volume=110\|issue=4\|pages=1112–1115\|doi=10.1182/blood-2006-07-038299\|issn=0006-4971\|pmc=1939895\|pmid=17473063}}</ref>.
	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-

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

2025-11-21T13:31:19Z

Individual Region Genomic Gain/Loss/LOH

← Older revision		Revision as of 08:31, 21 November 2025
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	==Individual Region Genomic Gain/Loss/LOH==		==Individual Region Genomic Gain/Loss/LOH==

	Please refer to section "Characteristic Chromosomal or Other Global Mutational Patterns" below.		Hypodiploid B-ALL is characterized by widespread genomic losses consistent with the hypodiploid karyotype<ref name=":13" />. Please refer to section "Characteristic Chromosomal or Other Global Mutational Patterns" below.
	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-

Miguel.GonzalezMancera: /* Genes and Main Pathways Involved */

2025-11-21T13:17:38Z

Genes and Main Pathways Involved

← Older revision		Revision as of 08:17, 21 November 2025
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	\|Constitutive activation of mitogenic and anti-apoptotic pathways, driving uncontrolled cell proliferation, survival, and malignant transformation.		\|Constitutive activation of mitogenic and anti-apoptotic pathways, driving uncontrolled cell proliferation, survival, and malignant transformation.
	\|-		\|-
	\|''CDKN2A/B, TP53, RB1''; Loss of function mutations		\|''CDKN2A/B, TP53, RB1''; Loss of function mutations<ref name=":2" />
	\|Cell cycle and apoptosis		\|Cell cycle and apoptosis
	\|Propagation of genetically altered cells.		\|Propagation of genetically altered cells.

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

2025-11-21T13:14:04Z

Gene Mutations (SNV/INDEL)

← Older revision		Revision as of 08:14, 21 November 2025
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	\|-		\|-
	\|''NF1''		\|''NF1''
	\|Mutations and focal deletions. In 68% of the cases, the ''NF1'' deletions were intragenic involving exons 15 through 35<ref name=":2" />.		\|Mutations and focal deletions. In 68% of the cases, the ''NF1'' deletions were intragenic involving exons 15 through 35. Because of aneuploidy, the ''NF1'' alterations were biallelic in 76.7% of near-haploid cases.<ref name=":2" />
	\|Tumor supressor gene		\|Tumor supressor gene
	\|Mutations: Recurrent		\|Mutations: Recurrent

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

2025-11-21T13:12:08Z

Characteristic Chromosomal or Other Global Mutational Patterns

← Older revision		Revision as of 08:12, 21 November 2025
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	\|No (NCCN)		\|No (NCCN)
	\|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.		\|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.
	\|}		\|}<blockquote class="blockedit">
			<center>
	~~<blockquote class="blockedit"></blockquote>~~<blockquote class="blockedit">
	<center~~><span style="color:Maroon">'''End of V4 Section'''</span~~>
	----		----
	</blockquote>		</blockquote>
	==Gene Mutations (SNV/INDEL)==		==Gene Mutations (SNV/INDEL)==
			Holmfeldt et al sequenced 124 cases of low-hypodiploid B-ALL and showed that more than two-thirds (70.6%) of near-haploid ALL cases harbored genetic alterations known or predicted to result in activation of RTK or Ras signaling, including deletion, amplification and/or sequence mutation of ''NF1'', ''NRAS'', ''KRAS'', ''MAPK1'', ''FLT3'' or ''PTPN11<ref name=":2" />''.
	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-
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	\|-		\|-
	\|''FLT3''		\|''FLT3''
	\|~~Mutations~~<ref name=":2" />		\|Mutation<ref name=":2" />
	\|Oncogene		\|Oncogene
	\|Recurrent		\|Recurrent
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	\|-		\|-
	\|''NRAS''		\|''NRAS''
	\|~~Mutations~~<ref name=":2" />		\|Mutation<ref name=":2" />
	\|Oncogene		\|Oncogene
	\|Recurrent		\|Recurrent
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	\|-		\|-
	\|''IKZF2''		\|''IKZF2''
	\|Focal deletion<ref name=":16" />		\|Focal deletion. Alterations of ''IKZF2'' and ''IKZF3'' were biallelic as a result of aneuploidy<ref name=":2" />.
	\|Tumor supressor		\|Tumor supressor
	\|Common		\|Common
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	\|''IKZF3''		\|''IKZF3''
	<br />		<br />
	\|Focal deletion<ref name=":16" />		\|Focal deletion and one frameshift mutation<ref name=":2" />
	\|Tumor supressor		\|Tumor supressor
	\|Recurrent		\|Recurrent
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	\|-		\|-
	\|''PAG1''		\|''PAG1''
	\|Focal deletion<ref name=":2" />		\|Focal deletion<ref name=":2" />. Most ''PAG1'' deletions were homozygous and involved the upstream region and first exon, leading to a complete loss of ''PAG1'' expression.
	\|Tumor supressor		\|Tumor supressor
	\|Recurrent		\|Recurrent
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	\|''IKZF1, IKZF2, IKZF3, PAX5, EBF1, VPREB1''		\|''IKZF1, IKZF2, IKZF3, PAX5, EBF1, VPREB1''
	\|B-cell development		\|B-cell development
	\|		\|Altered lymphoid development and differentiation.
			\|-
			\|''PAG1''
			\|BCR signaling
			\|Altered regulatory function in proximal B cell–receptor signaling.
	\|-		\|-
	\|''ETV6''		\|''ETV6''
	\|Hematopoiesis		\|Hematopoiesis
	\|		\|Not fully elucidated in this entity
	\|-
	~~\|''PAG1''~~
	~~\|BCR signaling~~
	\|
	\|-		\|-
	\|''ARPP21''		\|''ARPP21''
	\|Calmodulin signaling		\|Calmodulin signaling
	\|		\|Not fully elucidated in this entity
	\|-		\|-
	\|''SLX4IP''		\|''SLX4IP''
	\|Telomere length maintenance		\|Telomere length maintenance
	\|		\|Not fully elucidated in this entity
	\|-		\|-
	\|''CUL5''		\|''CUL5''
	\|Ubiquitin pathway		\|Ubiquitin pathway
	\|		\|Not fully elucidated in this entity
	\|-		\|-
	\|''FAM53B''		\|''FAM53B''
	\|Wnt signaling		\|Wnt signaling
	\|		\|Not fully elucidated in this entity
	\|-		\|-
	\|''PDS5B''		\|''PDS5B''
	\|Cohesis complex		\|Cohesis complex
	\|		\|Not fully elucidated in this entity
	\|-		\|-
	\|''ANKRD11, DMD''		\|''ANKRD11, DMD''
	\|Cell adhesion		\|Cell adhesion
	\|		\|Not fully elucidated in this entity
	\|}		\|}

Miguel.GonzalezMancera: /* Epigenomic Alterations */

2025-11-21T12:46:00Z

Epigenomic Alterations

← Older revision		Revision as of 07:46, 21 November 2025
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	==Epigenomic Alterations==		==Epigenomic Alterations==

	In near haploid 19% of the cases had focal deletions of histone gene cluster at 6p22, however, non-hypodiploid ALL had 8%, lower frequency of these deletions<ref name=":2" />.		In near haploid 19% of the cases had focal deletions of histone gene cluster at 6p22, however, non-hypodiploid ALL had 8%, lower frequency of these deletions<ref name=":2" />. Of the 25 next generation sequenced haploid cases 16 (64%) cases had twenty six histone modifier gene mutations and of the 15 low hypodiploid ALL cases 9 (60%) cases had 9 mutations; the most common mutation (32%) of the near haploid cases was transcriptional co-activator and histone acetyltransferase ''CREBBP''<ref name=":2" />.

	Of the 25 next generation sequenced haploid cases 16 (64%) cases had twenty six histone modifier gene mutations and of the 15 low hypodiploid ALL cases 9 (60%) cases had 9 mutations; the most common mutation (32%) of the near haploid cases was transcriptional co-activator and histone acetyltransferase ''CREBBP''<ref name=":2" />.

	==Genes and Main Pathways Involved==		==Genes and Main Pathways Involved==

Miguel.GonzalezMancera: /* Genes and Main Pathways Involved */

2025-11-20T15:24:07Z

Genes and Main Pathways Involved

← Older revision		Revision as of 10:24, 20 November 2025
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	\|RTK or Ras signaling		\|RTK or Ras signaling
	\|Constitutive activation of mitogenic and anti-apoptotic pathways, driving uncontrolled cell proliferation, survival, and malignant transformation.		\|Constitutive activation of mitogenic and anti-apoptotic pathways, driving uncontrolled cell proliferation, survival, and malignant transformation.
			\|-
			\|''CDKN2A/B, TP53, RB1''; Loss of function mutations
			\|Cell cycle and apoptosis
			\|Propagation of genetically altered cells.
	\|-		\|-
	\|''IKZF1, IKZF2, IKZF3, PAX5, EBF1, VPREB1''		\|''IKZF1, IKZF2, IKZF3, PAX5, EBF1, VPREB1''
	\|B-cell development		\|B-cell development
	\|		\|
	\|-
	~~\|''CDKN2A/B, TP53, RB1''; Loss of function mutations~~
	~~\|Cell cycle and apoptosis~~
	~~\|Propagation of genetically altered cells.~~
	\|-		\|-
	\|''ETV6''		\|''ETV6''
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	\|}		\|}

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

Miguel.GonzalezMancera: /* Genes and Main Pathways Involved */

2025-11-20T14:57:38Z

Genes and Main Pathways Involved

← Older revision		Revision as of 09:57, 20 November 2025
Line 264:		Line 264:
	\|		\|
	\|-		\|-
	\|''CDKN2A/B, TP53, RB1''		\|''CDKN2A/B, TP53, RB1''; Loss of function mutations
	\|Cell cycle and apoptosis		\|Cell cycle and apoptosis
	\|		\|Propagation of genetically altered cells.
	\|-		\|-
	\|''ETV6''		\|''ETV6''

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

2025-11-20T14:46:34Z

Characteristic Chromosomal or Other Global Mutational Patterns

Show changes