HAEM5:Acute myeloid leukaemia with RBM15::MRTFA fusion - Revision history

Bailey.Glen at 17:08, 3 July 2025

2025-07-03T17:08:05Z

← Older revision		Revision as of 12:08, 3 July 2025
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	\|}		\|}

	~~==WHO Essential and Desirable Genetic Diagnostic Criteria==~~
	~~{\| class="wikitable"~~
	\|+
	\|WHO Essential Criteria (Genetics)*
	~~\|Detection of ''RBM15''::''MRTFA'' fusion by FISH and/or RT-PCR or a similar molecular technique~~
	\|-
	\|WHO Desirable Criteria (Genetics)*
	~~\|Detection of t(1;22)(p13.3;q13.1) by karyotype analysis~~
	\|-
	~~\|Other Classification~~
	~~\|N/A~~
	\|}
	<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
	==Related Terminology==		==Related Terminology==

Bailey.Glen at 21:27, 25 May 2025

2025-05-25T21:27:29Z

← Older revision		Revision as of 16:27, 25 May 2025
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	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-
	!Chr #!!~~'''~~Gain, Loss, Amp, LOH~~'''~~!!~~'''~~Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]~~'''~~!!~~'''~~Relevant Gene(s)~~'''~~		!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
	!~~'''~~Diagnostic, Prognostic, and Therapeutic Significance - D, P, T~~'''~~		!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
	!~~'''~~Established Clinical Significance Per Guidelines - Yes or No (Source)~~'''~~		!Established Clinical Significance Per Guidelines - Yes or No (Source)
	!~~'''~~Clinical Relevance Details/Other Notes~~'''~~		!Clinical Relevance Details/Other Notes
	\|-		\|-
	\|N/A		\|N/A
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	!Chromosomal Pattern		!Chromosomal Pattern
	!Molecular Pathogenesis		!Molecular Pathogenesis
	!~~'''~~Prevalence -~~'''~~		!Prevalence -
	~~'''~~Common >20%, Recurrent 5-20% or Rare <5% (Disease)~~'''~~		Common >20%, Recurrent 5-20% or Rare <5% (Disease)
	!~~'''~~Diagnostic, Prognostic, and Therapeutic Significance - D, P, T~~'''~~		!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
	!~~'''~~Established Clinical Significance Per Guidelines - Yes or No (Source)~~'''~~		!Established Clinical Significance Per Guidelines - Yes or No (Source)
	!~~'''~~Clinical Relevance Details/Other Notes~~'''~~		!Clinical Relevance Details/Other Notes
	\|-		\|-
	\|N/A		\|N/A
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	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-
	!Gene!!~~'''~~Genetic Alteration~~'''~~!!~~'''~~Tumor Suppressor Gene, Oncogene, Other~~'''~~!!~~'''~~Prevalence -~~'''~~		!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
	~~'''~~Common >20%, Recurrent 5-20% or Rare <5% (Disease)~~'''~~		Common >20%, Recurrent 5-20% or Rare <5% (Disease)
	!~~'''~~Diagnostic, Prognostic, and Therapeutic Significance - D, P, T ~~'''~~		!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
	!~~'''~~Established Clinical Significance Per Guidelines - Yes or No (Source)~~'''~~		!Established Clinical Significance Per Guidelines - Yes or No (Source)
	!~~'''~~Clinical Relevance Details/Other Notes~~'''~~		!Clinical Relevance Details/Other Notes
	\|-		\|-
	\|N/A		\|N/A

Bailey.Glen at 20:03, 25 May 2025

2025-05-25T20:03:54Z

← Older revision		Revision as of 15:03, 25 May 2025
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	<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].		<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
	==Related Terminology==		==Related Terminology==
	~~<span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>~~
	{\| class="wikitable"		{\| class="wikitable"
	\|+		\|+
	\|Acceptable		\|Acceptable
	\|		\|Acute megakaryoblastic leukaemia with RBM15::MRTFA
	\|-		\|-
	\|Not Recommended		\|Not Recommended
	\|		\|Acute myeloid leukaemia with RBM15::MKL1; acute megakaryoblastic leukaemia with RBM15::MKL1; acute myeloid leukaemia with OTT::MAL
	\|}		\|}

Bailey.Glen at 19:20, 25 May 2025

2025-05-25T19:20:14Z

← Older revision		Revision as of 14:20, 25 May 2025
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	{{DISPLAYTITLE:Acute myeloid leukaemia with RBM15::MRTFA fusion}}		{{DISPLAYTITLE:Acute myeloid leukaemia with RBM15::MRTFA fusion}}

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

Jennelleh at 14:02, 17 May 2025

2025-05-17T14:02:28Z

← Older revision		Revision as of 09:02, 17 May 2025
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	==Genes and Main Pathways Involved==		==Genes and Main Pathways Involved==

	* The molecular mechanism is not completely understood, but the fusion protein may modulate chromatin organization, HOX-induced differentiation and extracellular signaling pathways associated with leukemogenesis<ref>{{Cite journal\|last=Mercher\|first=T.\|last2=Coniat\|first2=M. B.\|last3=Monni\|first3=R.\|last4=Mauchauffe\|first4=M.\|last5=Nguyen Khac\|first5=F.\|last6=Gressin\|first6=L.\|last7=Mugneret\|first7=F.\|last8=Leblanc\|first8=T.\|last9=Dastugue\|first9=N.\|date=2001-05-08\|title=Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/11344311\|journal=Proceedings of the National Academy of Sciences of the United States of America\|volume=98\|issue=10\|pages=5776–5779\|doi=10.1073/pnas.101001498\|issn=0027-8424\|pmc=33289\|pmid=11344311}}</ref>. The fusion of MKL1 to RBM15 deregulates the normal intracellular localization of MKL1 such that it is becomes constitutively localized to the nucleus, resulting in serum response factor (SRF) activation even in the absence of stimuli<ref>{{Cite journal\|last=Gruber\|first=Tanja A.\|last2=Downing\|first2=James R.\|date=2015-08-20\|title=The biology of pediatric acute megakaryoblastic leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/26186939\|journal=Blood\|volume=126\|issue=8\|pages=943–949\|doi=10.1182/blood-2015-05-567859\|issn=1528-0020\|pmc=4551356\|pmid=26186939}}</ref>. SRF is a transcription factor that regulates the expression of genes involved in cell growth, proliferation, and differentiation, as well as genes that control the actin cytoskeleton<ref>{{Cite journal\|last=Halene\|first=Stephanie\|last2=Gao\|first2=Yuan\|last3=Hahn\|first3=Katherine\|last4=Massaro\|first4=Stephanie\|last5=Italiano\|first5=Joseph E.\|last6=Schulz\|first6=Vincent\|last7=Lin\|first7=Sharon\|last8=Kupfer\|first8=Gary M.\|last9=Krause\|first9=Diane S.\|date=2010-09-16\|title=Serum response factor is an essential transcription factor in megakaryocytic maturation\|url=https://pubmed.ncbi.nlm.nih.gov/20525922\|journal=Blood\|volume=116\|issue=11\|pages=1942–1950\|doi=10.1182/blood-2010-01-261743\|issn=1528-0020\|pmc=3173990\|pmid=20525922}}</ref>. Of note, while a ''RBM15''::''MKL1'' fusion knock-in model mouse showed abnormal megakaryopoiesis, it was not sufficient to induce leukemia<ref>{{Cite journal\|last=Mercher\|first=Thomas\|last2=Raffel\|first2=Glen D.\|last3=Moore\|first3=Sandra A.\|last4=Cornejo\|first4=Melanie G.\|last5=Baudry-Bluteau\|first5=Dominique\|last6=Cagnard\|first6=Nicolas\|last7=Jesneck\|first7=Jonathan L.\|last8=Pikman\|first8=Yana\|last9=Cullen\|first9=Dana\|date=2009-04\|title=The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model\|url=https://pubmed.ncbi.nlm.nih.gov/19287095\|journal=The Journal of Clinical Investigation\|volume=119\|issue=4\|pages=852–864\|doi=10.1172/JCI35901\|issn=1558-8238\|pmc=2662544\|pmid=19287095}}</ref>.		*The molecular mechanism is not completely understood, but the fusion protein may modulate chromatin organization, HOX-induced differentiation and extracellular signaling pathways associated with leukemogenesis<ref>{{Cite journal\|last=Mercher\|first=T.\|last2=Coniat\|first2=M. B.\|last3=Monni\|first3=R.\|last4=Mauchauffe\|first4=M.\|last5=Nguyen Khac\|first5=F.\|last6=Gressin\|first6=L.\|last7=Mugneret\|first7=F.\|last8=Leblanc\|first8=T.\|last9=Dastugue\|first9=N.\|date=2001-05-08\|title=Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/11344311\|journal=Proceedings of the National Academy of Sciences of the United States of America\|volume=98\|issue=10\|pages=5776–5779\|doi=10.1073/pnas.101001498\|issn=0027-8424\|pmc=33289\|pmid=11344311}}</ref>. The fusion of MKL1 to RBM15 deregulates the normal intracellular localization of MKL1 such that it is becomes constitutively localized to the nucleus, resulting in serum response factor (SRF) activation even in the absence of stimuli<ref>{{Cite journal\|last=Gruber\|first=Tanja A.\|last2=Downing\|first2=James R.\|date=2015-08-20\|title=The biology of pediatric acute megakaryoblastic leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/26186939\|journal=Blood\|volume=126\|issue=8\|pages=943–949\|doi=10.1182/blood-2015-05-567859\|issn=1528-0020\|pmc=4551356\|pmid=26186939}}</ref>. SRF is a transcription factor that regulates the expression of genes involved in cell growth, proliferation, and differentiation, as well as genes that control the actin cytoskeleton<ref>{{Cite journal\|last=Halene\|first=Stephanie\|last2=Gao\|first2=Yuan\|last3=Hahn\|first3=Katherine\|last4=Massaro\|first4=Stephanie\|last5=Italiano\|first5=Joseph E.\|last6=Schulz\|first6=Vincent\|last7=Lin\|first7=Sharon\|last8=Kupfer\|first8=Gary M.\|last9=Krause\|first9=Diane S.\|date=2010-09-16\|title=Serum response factor is an essential transcription factor in megakaryocytic maturation\|url=https://pubmed.ncbi.nlm.nih.gov/20525922\|journal=Blood\|volume=116\|issue=11\|pages=1942–1950\|doi=10.1182/blood-2010-01-261743\|issn=1528-0020\|pmc=3173990\|pmid=20525922}}</ref>. Of note, while a ''RBM15''::''MKL1'' fusion knock-in model mouse showed abnormal megakaryopoiesis, it was not sufficient to induce leukemia<ref>{{Cite journal\|last=Mercher\|first=Thomas\|last2=Raffel\|first2=Glen D.\|last3=Moore\|first3=Sandra A.\|last4=Cornejo\|first4=Melanie G.\|last5=Baudry-Bluteau\|first5=Dominique\|last6=Cagnard\|first6=Nicolas\|last7=Jesneck\|first7=Jonathan L.\|last8=Pikman\|first8=Yana\|last9=Cullen\|first9=Dana\|date=2009-04\|title=The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model\|url=https://pubmed.ncbi.nlm.nih.gov/19287095\|journal=The Journal of Clinical Investigation\|volume=119\|issue=4\|pages=852–864\|doi=10.1172/JCI35901\|issn=1558-8238\|pmc=2662544\|pmid=19287095}}</ref>.

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

	Karyotype, FISH, RT-PCR		Karyotype, FISH, RT-PCR (and any other fusion detecting technologies)

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

Jennelleh at 21:52, 13 May 2025

2025-05-13T21:52:22Z

← Older revision		Revision as of 16:52, 13 May 2025
Line 134:		Line 134:
	==Genes and Main Pathways Involved==		==Genes and Main Pathways Involved==

	The molecular mechanism is not completely understood, but the fusion protein may modulate chromatin organization, HOX-induced differentiation and extracellular signaling pathways associated with leukemogenesis<ref>{{Cite journal\|last=Mercher\|first=T.\|last2=Coniat\|first2=M. B.\|last3=Monni\|first3=R.\|last4=Mauchauffe\|first4=M.\|last5=Nguyen Khac\|first5=F.\|last6=Gressin\|first6=L.\|last7=Mugneret\|first7=F.\|last8=Leblanc\|first8=T.\|last9=Dastugue\|first9=N.\|date=2001-05-08\|title=Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/11344311\|journal=Proceedings of the National Academy of Sciences of the United States of America\|volume=98\|issue=10\|pages=5776–5779\|doi=10.1073/pnas.101001498\|issn=0027-8424\|pmc=33289\|pmid=11344311}}</ref>. The fusion of MKL1 to RBM15 deregulates the normal intracellular localization of MKL1 such that it is becomes constitutively localized to the nucleus, resulting in serum response factor (SRF) activation even in the absence of stimuli<ref>{{Cite journal\|last=Gruber\|first=Tanja A.\|last2=Downing\|first2=James R.\|date=2015-08-20\|title=The biology of pediatric acute megakaryoblastic leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/26186939\|journal=Blood\|volume=126\|issue=8\|pages=943–949\|doi=10.1182/blood-2015-05-567859\|issn=1528-0020\|pmc=4551356\|pmid=26186939}}</ref>. SRF is a transcription factor that regulates the expression of genes involved in cell growth, proliferation, and differentiation, as well as genes that control the actin cytoskeleton<ref>{{Cite journal\|last=Halene\|first=Stephanie\|last2=Gao\|first2=Yuan\|last3=Hahn\|first3=Katherine\|last4=Massaro\|first4=Stephanie\|last5=Italiano\|first5=Joseph E.\|last6=Schulz\|first6=Vincent\|last7=Lin\|first7=Sharon\|last8=Kupfer\|first8=Gary M.\|last9=Krause\|first9=Diane S.\|date=2010-09-16\|title=Serum response factor is an essential transcription factor in megakaryocytic maturation\|url=https://pubmed.ncbi.nlm.nih.gov/20525922\|journal=Blood\|volume=116\|issue=11\|pages=1942–1950\|doi=10.1182/blood-2010-01-261743\|issn=1528-0020\|pmc=3173990\|pmid=20525922}}</ref>. Of note, while a ''RBM15''::''MKL1'' fusion knock-in model mouse showed abnormal megakaryopoiesis, it was not sufficient to induce leukemia<ref>{{Cite journal\|last=Mercher\|first=Thomas\|last2=Raffel\|first2=Glen D.\|last3=Moore\|first3=Sandra A.\|last4=Cornejo\|first4=Melanie G.\|last5=Baudry-Bluteau\|first5=Dominique\|last6=Cagnard\|first6=Nicolas\|last7=Jesneck\|first7=Jonathan L.\|last8=Pikman\|first8=Yana\|last9=Cullen\|first9=Dana\|date=2009-04\|title=The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model\|url=https://pubmed.ncbi.nlm.nih.gov/19287095\|journal=The Journal of Clinical Investigation\|volume=119\|issue=4\|pages=852–864\|doi=10.1172/JCI35901\|issn=1558-8238\|pmc=2662544\|pmid=19287095}}</ref>.		* The molecular mechanism is not completely understood, but the fusion protein may modulate chromatin organization, HOX-induced differentiation and extracellular signaling pathways associated with leukemogenesis<ref>{{Cite journal\|last=Mercher\|first=T.\|last2=Coniat\|first2=M. B.\|last3=Monni\|first3=R.\|last4=Mauchauffe\|first4=M.\|last5=Nguyen Khac\|first5=F.\|last6=Gressin\|first6=L.\|last7=Mugneret\|first7=F.\|last8=Leblanc\|first8=T.\|last9=Dastugue\|first9=N.\|date=2001-05-08\|title=Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/11344311\|journal=Proceedings of the National Academy of Sciences of the United States of America\|volume=98\|issue=10\|pages=5776–5779\|doi=10.1073/pnas.101001498\|issn=0027-8424\|pmc=33289\|pmid=11344311}}</ref>. The fusion of MKL1 to RBM15 deregulates the normal intracellular localization of MKL1 such that it is becomes constitutively localized to the nucleus, resulting in serum response factor (SRF) activation even in the absence of stimuli<ref>{{Cite journal\|last=Gruber\|first=Tanja A.\|last2=Downing\|first2=James R.\|date=2015-08-20\|title=The biology of pediatric acute megakaryoblastic leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/26186939\|journal=Blood\|volume=126\|issue=8\|pages=943–949\|doi=10.1182/blood-2015-05-567859\|issn=1528-0020\|pmc=4551356\|pmid=26186939}}</ref>. SRF is a transcription factor that regulates the expression of genes involved in cell growth, proliferation, and differentiation, as well as genes that control the actin cytoskeleton<ref>{{Cite journal\|last=Halene\|first=Stephanie\|last2=Gao\|first2=Yuan\|last3=Hahn\|first3=Katherine\|last4=Massaro\|first4=Stephanie\|last5=Italiano\|first5=Joseph E.\|last6=Schulz\|first6=Vincent\|last7=Lin\|first7=Sharon\|last8=Kupfer\|first8=Gary M.\|last9=Krause\|first9=Diane S.\|date=2010-09-16\|title=Serum response factor is an essential transcription factor in megakaryocytic maturation\|url=https://pubmed.ncbi.nlm.nih.gov/20525922\|journal=Blood\|volume=116\|issue=11\|pages=1942–1950\|doi=10.1182/blood-2010-01-261743\|issn=1528-0020\|pmc=3173990\|pmid=20525922}}</ref>. Of note, while a ''RBM15''::''MKL1'' fusion knock-in model mouse showed abnormal megakaryopoiesis, it was not sufficient to induce leukemia<ref>{{Cite journal\|last=Mercher\|first=Thomas\|last2=Raffel\|first2=Glen D.\|last3=Moore\|first3=Sandra A.\|last4=Cornejo\|first4=Melanie G.\|last5=Baudry-Bluteau\|first5=Dominique\|last6=Cagnard\|first6=Nicolas\|last7=Jesneck\|first7=Jonathan L.\|last8=Pikman\|first8=Yana\|last9=Cullen\|first9=Dana\|date=2009-04\|title=The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model\|url=https://pubmed.ncbi.nlm.nih.gov/19287095\|journal=The Journal of Clinical Investigation\|volume=119\|issue=4\|pages=852–864\|doi=10.1172/JCI35901\|issn=1558-8238\|pmc=2662544\|pmid=19287095}}</ref>.

	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-

Jennelleh at 21:51, 13 May 2025

2025-05-13T21:51:45Z

← Older revision		Revision as of 16:51, 13 May 2025
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	\|-		\|-
	\|''RBM15'' and ''MKL1''		\|''RBM15'' and ''MKL1''
	\|''RBM15''(''OTT'')::''MKL1''(''MAL'')\|\|The majority of both genes retained in the fusion 5’ ''DEK'' and 3’''NUP214''(''CAN'') with the pathogenic derivative being ~~hte~~ der(22).\|\|t(1;22)(p13.3;q13.1)		\|''RBM15''(''OTT'')::''MKL1''(''MAL'')\|\|The majority of both genes are retained in the fusion, specifically 5’ ''DEK'' and 3’''NUP214''(''CAN''), with the pathogenic derivative being the der(22).\|\|t(1;22)(p13.3;q13.1)
	\|Rare (AML)		\|Rare (AML)
	\|D		\|D
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	==Gene Mutations (SNV/INDEL)==		==Gene Mutations (SNV/INDEL)==

	* COSMIC does not have specific information on mutations related to this subtype of AML.		*COSMIC does not have specific information on mutations related to this subtype of AML.

	{\| class="wikitable sortable"		{\| class="wikitable sortable"

Jennelleh at 21:45, 13 May 2025

2025-05-13T21:45:38Z

← Older revision		Revision as of 16:45, 13 May 2025
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	==Gene Mutations (SNV/INDEL)==		==Gene Mutations (SNV/INDEL)==

	COSMIC does not have specific information on mutations related to this subtype of AML.		* COSMIC does not have specific information on mutations related to this subtype of AML.

	{\| class="wikitable sortable"		{\| class="wikitable sortable"
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	==References==		==References==
	(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span> <references />		<references />

	<br />		<br />

Jennelleh at 21:44, 13 May 2025

2025-05-13T21:44:10Z

← Older revision		Revision as of 16:44, 13 May 2025
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	==Genes and Main Pathways Involved==		==Genes and Main Pathways Involved==

	The molecular mechanism is not completely understood, but the fusion protein may modulate chromatin organization, HOX-induced differentiation and extracellular signaling pathways associated with leukemogenesis<ref>{{Cite journal\|last=Mercher\|first=T.\|last2=Coniat\|first2=M. B.\|last3=Monni\|first3=R.\|last4=Mauchauffe\|first4=M.\|last5=Nguyen Khac\|first5=F.\|last6=Gressin\|first6=L.\|last7=Mugneret\|first7=F.\|last8=Leblanc\|first8=T.\|last9=Dastugue\|first9=N.\|date=2001-05-08\|title=Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/11344311\|journal=Proceedings of the National Academy of Sciences of the United States of America\|volume=98\|issue=10\|pages=5776–5779\|doi=10.1073/pnas.101001498\|issn=0027-8424\|pmc=33289\|pmid=11344311}}</ref>. The fusion of MKL1 to RBM15 deregulates the normal intracellular localization of MKL1 such that it is becomes constitutively localized to the nucleus, resulting in serum response factor (SRF) activation even in the absence of stimuli<ref>{{Cite journal\|last=Gruber\|first=Tanja A.\|last2=Downing\|first2=James R.\|date=2015-08-20\|title=The biology of pediatric acute megakaryoblastic leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/26186939\|journal=Blood\|volume=126\|issue=8\|pages=943–949\|doi=10.1182/blood-2015-05-567859\|issn=1528-0020\|pmc=4551356\|pmid=26186939}}</ref>. SRF is a transcription factor that regulates the expression of genes involved in cell growth, proliferation, and differentiation, as well as genes that control the actin cytoskeleton<ref>{{Cite journal\|last=Halene\|first=Stephanie\|last2=Gao\|first2=Yuan\|last3=Hahn\|first3=Katherine\|last4=Massaro\|first4=Stephanie\|last5=Italiano\|first5=Joseph E.\|last6=Schulz\|first6=Vincent\|last7=Lin\|first7=Sharon\|last8=Kupfer\|first8=Gary M.\|last9=Krause\|first9=Diane S.\|date=2010-09-16\|title=Serum response factor is an essential transcription factor in megakaryocytic maturation\|url=https://pubmed.ncbi.nlm.nih.gov/20525922\|journal=Blood\|volume=116\|issue=11\|pages=1942–1950\|doi=10.1182/blood-2010-01-261743\|issn=1528-0020\|pmc=3173990\|pmid=20525922}}</ref>. Of note, while a ''RBM15''::''MKL1'' fusion knock-in model mouse ~~shoed~~ abnormal megakaryopoiesis, it was not sufficient to induce leukemia<ref>{{Cite journal\|last=Mercher\|first=Thomas\|last2=Raffel\|first2=Glen D.\|last3=Moore\|first3=Sandra A.\|last4=Cornejo\|first4=Melanie G.\|last5=Baudry-Bluteau\|first5=Dominique\|last6=Cagnard\|first6=Nicolas\|last7=Jesneck\|first7=Jonathan L.\|last8=Pikman\|first8=Yana\|last9=Cullen\|first9=Dana\|date=2009-04\|title=The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model\|url=https://pubmed.ncbi.nlm.nih.gov/19287095\|journal=The Journal of Clinical Investigation\|volume=119\|issue=4\|pages=852–864\|doi=10.1172/JCI35901\|issn=1558-8238\|pmc=2662544\|pmid=19287095}}</ref>.		The molecular mechanism is not completely understood, but the fusion protein may modulate chromatin organization, HOX-induced differentiation and extracellular signaling pathways associated with leukemogenesis<ref>{{Cite journal\|last=Mercher\|first=T.\|last2=Coniat\|first2=M. B.\|last3=Monni\|first3=R.\|last4=Mauchauffe\|first4=M.\|last5=Nguyen Khac\|first5=F.\|last6=Gressin\|first6=L.\|last7=Mugneret\|first7=F.\|last8=Leblanc\|first8=T.\|last9=Dastugue\|first9=N.\|date=2001-05-08\|title=Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/11344311\|journal=Proceedings of the National Academy of Sciences of the United States of America\|volume=98\|issue=10\|pages=5776–5779\|doi=10.1073/pnas.101001498\|issn=0027-8424\|pmc=33289\|pmid=11344311}}</ref>. The fusion of MKL1 to RBM15 deregulates the normal intracellular localization of MKL1 such that it is becomes constitutively localized to the nucleus, resulting in serum response factor (SRF) activation even in the absence of stimuli<ref>{{Cite journal\|last=Gruber\|first=Tanja A.\|last2=Downing\|first2=James R.\|date=2015-08-20\|title=The biology of pediatric acute megakaryoblastic leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/26186939\|journal=Blood\|volume=126\|issue=8\|pages=943–949\|doi=10.1182/blood-2015-05-567859\|issn=1528-0020\|pmc=4551356\|pmid=26186939}}</ref>. SRF is a transcription factor that regulates the expression of genes involved in cell growth, proliferation, and differentiation, as well as genes that control the actin cytoskeleton<ref>{{Cite journal\|last=Halene\|first=Stephanie\|last2=Gao\|first2=Yuan\|last3=Hahn\|first3=Katherine\|last4=Massaro\|first4=Stephanie\|last5=Italiano\|first5=Joseph E.\|last6=Schulz\|first6=Vincent\|last7=Lin\|first7=Sharon\|last8=Kupfer\|first8=Gary M.\|last9=Krause\|first9=Diane S.\|date=2010-09-16\|title=Serum response factor is an essential transcription factor in megakaryocytic maturation\|url=https://pubmed.ncbi.nlm.nih.gov/20525922\|journal=Blood\|volume=116\|issue=11\|pages=1942–1950\|doi=10.1182/blood-2010-01-261743\|issn=1528-0020\|pmc=3173990\|pmid=20525922}}</ref>. Of note, while a ''RBM15''::''MKL1'' fusion knock-in model mouse showed abnormal megakaryopoiesis, it was not sufficient to induce leukemia<ref>{{Cite journal\|last=Mercher\|first=Thomas\|last2=Raffel\|first2=Glen D.\|last3=Moore\|first3=Sandra A.\|last4=Cornejo\|first4=Melanie G.\|last5=Baudry-Bluteau\|first5=Dominique\|last6=Cagnard\|first6=Nicolas\|last7=Jesneck\|first7=Jonathan L.\|last8=Pikman\|first8=Yana\|last9=Cullen\|first9=Dana\|date=2009-04\|title=The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model\|url=https://pubmed.ncbi.nlm.nih.gov/19287095\|journal=The Journal of Clinical Investigation\|volume=119\|issue=4\|pages=852–864\|doi=10.1172/JCI35901\|issn=1558-8238\|pmc=2662544\|pmid=19287095}}</ref>.
	{\| class="wikitable sortable"		{\| class="wikitable sortable"
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	\|''RBM15'' and ''MKL1''; Gain-of-function		\|''RBM15'' and ''MKL1''; Gain-of-function
	\|HOX signaling		\|HOX and other signaling pathways
	\|		\|Abnormal megakaryopoiesis
	\|}		\|}
	==Genetic Diagnostic Testing Methods==		==Genetic Diagnostic Testing Methods==

Jennelleh at 21:42, 13 May 2025

2025-05-13T21:42:57Z

← Older revision		Revision as of 16:42, 13 May 2025
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	==Genes and Main Pathways Involved==		==Genes and Main Pathways Involved==

	The molecular mechanism is not completely understood, but the fusion protein may modulate chromatin organization, HOX-induced differentiation and extracellular signaling pathways<ref ~~name~~=":1" /><ref ~~name~~=":3" />.		The molecular mechanism is not completely understood, but the fusion protein may modulate chromatin organization, HOX-induced differentiation and extracellular signaling pathways associated with leukemogenesis<ref>{{Cite journal\|last=Mercher\|first=T.\|last2=Coniat\|first2=M. B.\|last3=Monni\|first3=R.\|last4=Mauchauffe\|first4=M.\|last5=Nguyen Khac\|first5=F.\|last6=Gressin\|first6=L.\|last7=Mugneret\|first7=F.\|last8=Leblanc\|first8=T.\|last9=Dastugue\|first9=N.\|date=2001-05-08\|title=Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/11344311\|journal=Proceedings of the National Academy of Sciences of the United States of America\|volume=98\|issue=10\|pages=5776–5779\|doi=10.1073/pnas.101001498\|issn=0027-8424\|pmc=33289\|pmid=11344311}}</ref>. The fusion of MKL1 to RBM15 deregulates the normal intracellular localization of MKL1 such that it is becomes constitutively localized to the nucleus, resulting in serum response factor (SRF) activation even in the absence of stimuli<ref>{{Cite journal\|last=Gruber\|first=Tanja A.\|last2=Downing\|first2=James R.\|date=2015-08-20\|title=The biology of pediatric acute megakaryoblastic leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/26186939\|journal=Blood\|volume=126\|issue=8\|pages=943–949\|doi=10.1182/blood-2015-05-567859\|issn=1528-0020\|pmc=4551356\|pmid=26186939}}</ref>. SRF is a transcription factor that regulates the expression of genes involved in cell growth, proliferation, and differentiation, as well as genes that control the actin cytoskeleton<ref>{{Cite journal\|last=Halene\|first=Stephanie\|last2=Gao\|first2=Yuan\|last3=Hahn\|first3=Katherine\|last4=Massaro\|first4=Stephanie\|last5=Italiano\|first5=Joseph E.\|last6=Schulz\|first6=Vincent\|last7=Lin\|first7=Sharon\|last8=Kupfer\|first8=Gary M.\|last9=Krause\|first9=Diane S.\|date=2010-09-16\|title=Serum response factor is an essential transcription factor in megakaryocytic maturation\|url=https://pubmed.ncbi.nlm.nih.gov/20525922\|journal=Blood\|volume=116\|issue=11\|pages=1942–1950\|doi=10.1182/blood-2010-01-261743\|issn=1528-0020\|pmc=3173990\|pmid=20525922}}</ref>. Of note, while a ''RBM15''::''MKL1'' fusion knock-in model mouse shoed abnormal megakaryopoiesis, it was not sufficient to induce leukemia<ref>{{Cite journal\|last=Mercher\|first=Thomas\|last2=Raffel\|first2=Glen D.\|last3=Moore\|first3=Sandra A.\|last4=Cornejo\|first4=Melanie G.\|last5=Baudry-Bluteau\|first5=Dominique\|last6=Cagnard\|first6=Nicolas\|last7=Jesneck\|first7=Jonathan L.\|last8=Pikman\|first8=Yana\|last9=Cullen\|first9=Dana\|date=2009-04\|title=The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model\|url=https://pubmed.ncbi.nlm.nih.gov/19287095\|journal=The Journal of Clinical Investigation\|volume=119\|issue=4\|pages=852–864\|doi=10.1172/JCI35901\|issn=1558-8238\|pmc=2662544\|pmid=19287095}}</ref>.
	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-
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	\|''RBM15'' and ''MKL1''; Gain-of-function		\|''RBM15'' and ''MKL1''; Gain-of-function
	\|~~<span class="blue-text">EXAMPLE:</span> MAPK~~ signaling		\|HOX signaling
	\|~~<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation~~		\|
	\|}		\|}
	==Genetic Diagnostic Testing Methods==		==Genetic Diagnostic Testing Methods==