Bailey.Glen at 21:27, 4 December 2023

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← Older revision		Revision as of 16:27, 4 December 2023
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	==Chromosomal Rearrangements (Gene Fusions)==		==Chromosomal Rearrangements (Gene Fusions)==

	The ''RUNX1'' gene is involved in the 8;21 translocation (see [http://www.ccga.io/index.php/~~Acute_Myeloid_Leukemia_(AML)_with_t(8;21)(q22;q22.1);_RUNX1-RUNX1T1~~ Acute Myeloid Leukemia (AML) with t(8;21)(q22;q22.1); RUNX1-RUNX1T1] page), but the AML with mutated ''RUNX1'' subcategory is specific for those cases with a somatic, acquired mutation in the ''RUNX1'' gene.		The ''RUNX1'' gene is involved in the 8;21 translocation (see [http://www.ccga.io/index.php/HAEM5:Acute_myeloid_leukaemia_with_RUNX1::RUNX1T1_fusion Acute Myeloid Leukemia (AML) with t(8;21)(q22;q22.1); RUNX1-RUNX1T1] page), but the AML with mutated ''RUNX1'' subcategory is specific for those cases with a somatic, acquired mutation in the ''RUNX1'' gene.

	==Characteristic Chromosomal Aberrations / Patterns==		==Characteristic Chromosomal Aberrations / Patterns==

Bailey.Glen at 18:45, 3 November 2023

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 ==Primary Author(s)*==
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 ==Notes==
 <nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
+[[Category:HAEM4]] [[Category:DISEASE]]

Bailey.Glen: Created page with "==Primary Author(s)*== Iris Martin, M.D. Daynna J. Wolff, Ph.D. TOC ==Cancer Category/Type== Acute Myeloid Leukemia ==Cancer Sub-Classification / Subtype== Acute My..."

2023-11-03T18:05:24Z

Created page with "==Primary Author(s)*== Iris Martin, M.D. Daynna J. Wolff, Ph.D. __TOC__ ==Cancer Category/Type== Acute Myeloid Leukemia ==Cancer Sub-Classification / Subtype== Acute My..."

New page

==Primary Author(s)*==

Iris Martin, M.D.

Daynna J. Wolff, Ph.D.

__TOC__

==Cancer Category/Type==

Acute Myeloid Leukemia

==Cancer Sub-Classification / Subtype==

Acute Myeloid Leukemia (AML) with mutated RUNX1<ref name=":0">Arber DA, et al., (2017). Acute myeloid leukaemia 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. Revised 4th Edition. IARC Press: Lyon, France, p144-145.</ref>

==Definition / Description of Disease==

Mutations in ''RUNX1'' are recurrent in ''de novo'' acute myeloid leukemia (AML). The runt-related transcription factor 1 (''RUNX1'') gene at chromosomal band 21q22 is instrumental in regulating hematopoiesis, and when disrupted, leads to a preleukemic state. RUNX1 interacts with core binding factor beta to form the core factor binding complex. The RUNX1 protein activates genes that control hematopoiesis, particularly in the development of hematopoietic stem cells (see https://ghr.nlm.nih.gov/gene/RUNX1). The RUNX1 protein has two functional domains an N-terminal RUNT domain, which mediates DNA-binding as well as an interaction with core-binding-factor beta (''CBFB''), and a C-terminal transactivation domain.

==Synonyms / Terminology==

None

==Epidemiology / Prevalence==

AML with mutated ''RUNX1'' has been reported in approximately 3% of pediatric and 15% of adult de novo AML patients<ref name=":1">{{Cite journal|last=Tang|first=Jih-Luh|last2=Hou|first2=Hsin-An|last3=Chen|first3=Chien-Yuan|last4=Liu|first4=Chieh-Yu|last5=Chou|first5=Wen-Chien|last6=Tseng|first6=Mei-Hsuan|last7=Huang|first7=Chi-Fei|last8=Lee|first8=Fen-Yu|last9=Liu|first9=Ming-Chih|date=2009|title=AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations|url=https://www.ncbi.nlm.nih.gov/pubmed/19808697|journal=Blood|volume=114|issue=26|pages=5352–5361|doi=10.1182/blood-2009-05-223784|issn=1528-0020|pmid=19808697}}</ref><ref name=":2">{{Cite journal|last=Greif|first=Philipp A.|last2=Konstandin|first2=Nikola P.|last3=Metzeler|first3=Klaus H.|last4=Herold|first4=Tobias|last5=Pasalic|first5=Zlatana|last6=Ksienzyk|first6=Bianka|last7=Dufour|first7=Annika|last8=Schneider|first8=Friederike|last9=Schneider|first9=Stephanie|date=2012|title=RUNX1 mutations in cytogenetically normal acute myeloid leukemia are associated with a poor prognosis and up-regulation of lymphoid genes|url=https://www.ncbi.nlm.nih.gov/pubmed/22689681|journal=Haematologica|volume=97|issue=12|pages=1909–1915|doi=10.3324/haematol.2012.064667|issn=1592-8721|pmc=3590097|pmid=22689681}}</ref><ref name=":3">{{Cite journal|last=Mendler|first=Jason H.|last2=Maharry|first2=Kati|last3=Radmacher|first3=Michael D.|last4=Mrózek|first4=Krzysztof|last5=Becker|first5=Heiko|last6=Metzeler|first6=Klaus H.|last7=Schwind|first7=Sebastian|last8=Whitman|first8=Susan P.|last9=Khalife|first9=Jihane|date=2012|title=RUNX1 mutations are associated with poor outcome in younger and older patients with cytogenetically normal acute myeloid leukemia and with distinct gene and MicroRNA expression signatures|url=https://www.ncbi.nlm.nih.gov/pubmed/22753902|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=30|issue=25|pages=3109–3118|doi=10.1200/JCO.2011.40.6652|issn=1527-7755|pmc=3732007|pmid=22753902}}</ref><ref>{{Cite journal|last=Schuback|first=Heather L.|last2=Arceci|first2=Robert J.|last3=Meshinchi|first3=Soheil|date=2013|title=Somatic characterization of pediatric acute myeloid leukemia using next-generation sequencing|url=https://www.ncbi.nlm.nih.gov/pubmed/24246700|journal=Seminars in Hematology|volume=50|issue=4|pages=325–332|doi=10.1053/j.seminhematol.2013.09.003|issn=1532-8686|pmid=24246700}}</ref>. RUNX1 mutations are associated with older age<ref name=":0" /> and one study suggested an association with male gender<ref name=":1" />.

==Clinical Features==

Patients with AML with mutated ''RUNX1'' have been reported to have a higher bone marrow blast count, although peripheral blood blasts are decreased. Hemoglobin, white blood cell count, and lactate dehydrogenase are all lower in these patients in comparison to those with wildtype ''RUNX1''<ref name=":0" />. AML patients with ''RUNX1'' mutation reportedly demonstrate reduced complete remission rate, poorer relapse-free survival, and poorer overall survival<ref name=":1" /><ref name=":4">{{Cite journal|last=Gaidzik|first=Verena I.|last2=Bullinger|first2=Lars|last3=Schlenk|first3=Richard F.|last4=Zimmermann|first4=Andreas S.|last5=Röck|first5=Jürgen|last6=Paschka|first6=Peter|last7=Corbacioglu|first7=Andrea|last8=Krauter|first8=Jürgen|last9=Schlegelberger|first9=Brigitte|date=2011|title=RUNX1 mutations in acute myeloid leukemia: results from a comprehensive genetic and clinical analysis from the AML study group|url=https://www.ncbi.nlm.nih.gov/pubmed/21343560|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=29|issue=10|pages=1364–1372|doi=10.1200/JCO.2010.30.7926|issn=1527-7755|pmid=21343560}}</ref><ref name=":5">{{Cite journal|last=Schnittger|first=Susanne|last2=Dicker|first2=Frank|last3=Kern|first3=Wolfgang|last4=Wendland|first4=Nicole|last5=Sundermann|first5=Jana|last6=Alpermann|first6=Tamara|last7=Haferlach|first7=Claudia|last8=Haferlach|first8=Torsten|date=2011|title=RUNX1 mutations are frequent in de novo AML with noncomplex karyotype and confer an unfavorable prognosis|url=https://www.ncbi.nlm.nih.gov/pubmed/21148331|journal=Blood|volume=117|issue=8|pages=2348–2357|doi=10.1182/blood-2009-11-255976|issn=1528-0020|pmid=21148331}}</ref><ref name=":6">{{Cite journal|last=Gaidzik|first=V. I.|last2=Teleanu|first2=V.|last3=Papaemmanuil|first3=E.|last4=Weber|first4=D.|last5=Paschka|first5=P.|last6=Hahn|first6=J.|last7=Wallrabenstein|first7=T.|last8=Kolbinger|first8=B.|last9=Köhne|first9=C. H.|date=2016|title=RUNX1 mutations in acute myeloid leukemia are associated with distinct clinico-pathologic and genetic features|url=https://www.ncbi.nlm.nih.gov/pubmed/27804971|journal=Leukemia|volume=30|issue=11|pages=2282|doi=10.1038/leu.2016.207|issn=1476-5551|pmid=27804971}}</ref><ref name=":7">{{Cite journal|last=Metzeler|first=Klaus H.|last2=Herold|first2=Tobias|last3=Rothenberg-Thurley|first3=Maja|last4=Amler|first4=Susanne|last5=Sauerland|first5=Maria C.|last6=Görlich|first6=Dennis|last7=Schneider|first7=Stephanie|last8=Konstandin|first8=Nikola P.|last9=Dufour|first9=Annika|date=2016|title=Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/27288520|journal=Blood|volume=128|issue=5|pages=686–698|doi=10.1182/blood-2016-01-693879|issn=1528-0020|pmid=27288520}}</ref>. The NCCN guidelines (v.1.2018) state that ''RUNX1'' mutations have been associated with poor prognosis in AML, whereas 2017 European LeukemiaNet (ELN) recommendations for AML<ref name=":8">{{Cite journal|last=Bullinger|first=Lars|last2=Döhner|first2=Konstanze|last3=Döhner|first3=Hartmut|date=2017|title=Genomics of Acute Myeloid Leukemia Diagnosis and Pathways|url=https://www.ncbi.nlm.nih.gov/pubmed/28297624|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=35|issue=9|pages=934–946|doi=10.1200/JCO.2016.71.2208|issn=1527-7755|pmid=28297624}}</ref><ref name=":9">{{Cite journal|last=Döhner|first=Hartmut|last2=Estey|first2=Elihu|last3=Grimwade|first3=David|last4=Amadori|first4=Sergio|last5=Appelbaum|first5=Frederick R.|last6=Büchner|first6=Thomas|last7=Dombret|first7=Hervé|last8=Ebert|first8=Benjamin L.|last9=Fenaux|first9=Pierre|date=2017|title=Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel|url=https://www.ncbi.nlm.nih.gov/pubmed/27895058|journal=Blood|volume=129|issue=4|pages=424–447|doi=10.1182/blood-2016-08-733196|issn=1528-0020|pmc=5291965|pmid=27895058}}</ref> have placed AML patients with mutated ''RUNX1'' in the absence of favorable risk markers in the adverse risk category. There are no therapies directly targeting inactivating alterations in ''RUNX1''. Preclinical studies suggest that ''RUNX1'' mutation may lead to the epigenetic repression of genes involved in apoptosis; treatment with DNA methyltransferase (''DNMT'') inhibitors may relieve this inhibition<ref name=":10">{{Cite journal|last=Saunthararajah|first=Yogen|last2=Triozzi|first2=Pierre|last3=Rini|first3=Brian|last4=Singh|first4=Arun|last5=Radivoyevitch|first5=Tomas|last6=Sekeres|first6=Mikkael|last7=Advani|first7=Anjali|last8=Tiu|first8=Ramon|last9=Reu|first9=Frederic|date=2012|title=p53-Independent, normal stem cell sparing epigenetic differentiation therapy for myeloid and other malignancies|url=https://www.ncbi.nlm.nih.gov/pubmed/22289496|journal=Seminars in Oncology|volume=39|issue=1|pages=97–108|doi=10.1053/j.seminoncol.2011.11.011|issn=1532-8708|pmc=3655437|pmid=22289496}}</ref>. Co-occurrence of ''RUNX1'' and ''ASXL1'' mutation in AML patients has been linked to poor prognosis, including decreased response to induction therapy, increased risk of death, and decreased event-free and overall survival<ref name=":6" /><ref name=":11">{{Cite journal|last=Paschka|first=Peter|last2=Schlenk|first2=Richard F.|last3=Gaidzik|first3=Verena I.|last4=Herzig|first4=Julia K.|last5=Aulitzky|first5=Teresa|last6=Bullinger|first6=Lars|last7=Späth|first7=Daniela|last8=Teleanu|first8=Veronika|last9=Kündgen|first9=Andrea|date=2015|title=ASXL1 mutations in younger adult patients with acute myeloid leukemia: a study by the German-Austrian Acute Myeloid Leukemia Study Group|url=https://www.ncbi.nlm.nih.gov/pubmed/25596267|journal=Haematologica|volume=100|issue=3|pages=324–330|doi=10.3324/haematol.2014.114157|issn=1592-8721|pmc=4349270|pmid=25596267}}</ref><ref name=":12">{{Cite journal|last=Krauth|first=M.-T.|last2=Eder|first2=C.|last3=Alpermann|first3=T.|last4=Bacher|first4=U.|last5=Nadarajah|first5=N.|last6=Kern|first6=W.|last7=Haferlach|first7=C.|last8=Haferlach|first8=T.|last9=Schnittger|first9=S.|date=2014|title=High number of additional genetic lesions in acute myeloid leukemia with t(8;21)/RUNX1-RUNX1T1: frequency and impact on clinical outcome|url=https://www.ncbi.nlm.nih.gov/pubmed/24402164|journal=Leukemia|volume=28|issue=7|pages=1449–1458|doi=10.1038/leu.2014.4|issn=1476-5551|pmid=24402164}}</ref>. The presence of ''RUNX1'' mutation in combination with either ''PHF6'' or ''SRSF2'' mutation has been associated with poor prognosis, as compared with patients not harboring a co-mutation, in one study of 2439 newly diagnosed adult AML patients<ref name=":6" />.

==Sites of Involvement==

The circulating blood and bone marrow are involved in cases of leukemia.

==Morphologic Features==

There are not unique morphologic characteristics for this type of AML. Common features such as large blasts with basophilic cytoplasm, large nuclei with fine chromatin, and cytoplasmic azurophilic granules been reported<ref name=":0" />. Several studies have indicated that the cells are typically immature (M0, M1 and M2) and exhibit undifferentiated morphology<ref name=":13">{{Cite journal|last=Haferlach|first=T.|last2=Stengel|first2=A.|last3=Eckstein|first3=S.|last4=Perglerová|first4=K.|last5=Alpermann|first5=T.|last6=Kern|first6=W.|last7=Haferlach|first7=C.|last8=Meggendorfer|first8=M.|date=2016|title=The new provisional WHO entity 'RUNX1 mutated AML' shows specific genetics but no prognostic influence of dysplasia|url=https://www.ncbi.nlm.nih.gov/pubmed/27211269|journal=Leukemia|volume=30|issue=10|pages=2109–2112|doi=10.1038/leu.2016.150|issn=1476-5551|pmc=5056958|pmid=27211269}}</ref>. Biallelic ''RUNX1'' mutations have been reported in AML-M0 patients who have a complete lack of RUNX1 function in their leukemic cells<ref>{{Cite journal|last=Preudhomme|first=C.|last2=Warot-Loze|first2=D.|last3=Roumier|first3=C.|last4=Grardel-Duflos|first4=N.|last5=Garand|first5=R.|last6=Lai|first6=J. L.|last7=Dastugue|first7=N.|last8=Macintyre|first8=E.|last9=Denis|first9=C.|date=2000|title=High incidence of biallelic point mutations in the Runt domain of the AML1/PEBP2 alpha B gene in Mo acute myeloid leukemia and in myeloid malignancies with acquired trisomy 21|url=https://www.ncbi.nlm.nih.gov/pubmed/11023523|journal=Blood|volume=96|issue=8|pages=2862–2869|issn=0006-4971|pmid=11023523}}</ref><ref>{{Cite journal|last=Roumier|first=Christophe|last2=Eclache|first2=Virginie|last3=Imbert|first3=Michelle|last4=Davi|first4=Frederic|last5=MacIntyre|first5=Elizabeth|last6=Garand|first6=Richard|last7=Talmant|first7=Pascaline|last8=Lepelley|first8=Pascale|last9=Lai|first9=Jean Luc|date=2003|title=M0 AML, clinical and biologic features of the disease, including AML1 gene mutations: a report of 59 cases by the Groupe Français d'Hématologie Cellulaire (GFHC) and the Groupe Français de Cytogénétique Hématologique (GFCH)|url=https://www.ncbi.nlm.nih.gov/pubmed/12393381|journal=Blood|volume=101|issue=4|pages=1277–1283|doi=10.1182/blood-2002-05-1474|issn=0006-4971|pmid=12393381}}</ref>.

==Immunophenotype==

Myeloblasts express CD13, CD34, and HLA-DR. There is variable expression of MPO, CD33, and monocytic markers.

{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||CD13
|-
|- |Positive (universal) || CD34
|-
|- |Positive (universal) || HLA-DR
|-
|Positive (subset)||MPO
|-
|Positive (subset)||CD33
|}

==Chromosomal Rearrangements (Gene Fusions)==

The ''RUNX1'' gene is involved in the 8;21 translocation (see [http://www.ccga.io/index.php/Acute_Myeloid_Leukemia_(AML)_with_t(8;21)(q22;q22.1);_RUNX1-RUNX1T1 Acute Myeloid Leukemia (AML) with t(8;21)(q22;q22.1); RUNX1-RUNX1T1] page), but the AML with mutated ''RUNX1'' subcategory is specific for those cases with a somatic, acquired mutation in the ''RUNX1'' gene.

==Characteristic Chromosomal Aberrations / Patterns==

Mutated ''RUNX1'' is more common in AML with a normal karyotype, but has also been associated with trisomies as sole abnormalities including +8, +13 (which is a rare entity) and even more rarely +11 and +14<ref name=":13" />. AML with mutated ''RUNX1'' has also been associated with loss of 7q<ref name=":8" />.

==Genomic Gain/Loss/LOH==

Not applicable.

==Gene Mutations (SNV/INDEL)==

''RUNX1'' mutations involve exons 3-5, the runt homology domain (RHD), and exons 6-8, the transactivation domain. These include intragenic altertions such as frameshift or missense mutations.

{| class="wikitable sortable"
|-
!Gene!!Mutation!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence (COSMIC/TCGA/Other)
|-
| || || || ||
|}

===Other Mutations===
''RUNX1'' mutations are frequently observed together with ''FLT3''-ITD, ''FLT3''-TKD, and ''MLL''-PTD and with mutations in ''SRSF2'' (25%), ''ASXL1'', ''IDH1'', ''IDH2'' and ''EZH2''<ref name=":0" /><ref name=":2" /><ref name=":2" /><ref name=":6" /><ref name=":8" /><ref name=":14">{{Cite journal|last=Sood|first=Raman|last2=Kamikubo|first2=Yasuhiko|last3=Liu|first3=Paul|date=2017|title=Role of RUNX1 in hematological malignancies|url=https://www.ncbi.nlm.nih.gov/pubmed/28179279|journal=Blood|volume=129|issue=15|pages=2070–2082|doi=10.1182/blood-2016-10-687830|issn=1528-0020|pmc=5391618|pmid=28179279}}</ref>. ''RUNX1'' and ''NPM1'' mutations have been reported to be mutually exclusive<ref name=":2" /><ref name=":3" /><ref name=":6" /><ref name=":14" />.

{| class="wikitable sortable"
|-
!Type!!Gene/Region/Other
|-
|Concomitant Mutations||
|-
|Secondary Mutations||
|-
|Mutually Exclusive||''RUNX1'' and ''NPM1''
|}

==Epigenomics (Methylation)==

Not applicable.

==Genes and Main Pathways Involved==

The ''RUNX1'' gene spans ∼261 kb on 21q and is a transcription factor which both activates and represses transcription, and is involved in developmental gene-expression programs and hematopoiesis. ''RUNX1'' is a frequent site of translocation and mutation in myeloid cancers and the Runx1 protein functions as a tumor suppressor in this context<ref>{{Cite journal|last=Silva|first=Fernando P. G.|last2=Morolli|first2=Bruno|last3=Storlazzi|first3=Clelia T.|last4=Anelli|first4=Luisa|last5=Wessels|first5=Hans|last6=Bezrookove|first6=Vladimir|last7=Kluin-Nelemans|first7=Hanneke C.|last8=Giphart-Gassler|first8=Micheline|date=2003|title=Identification of RUNX1/AML1 as a classical tumor suppressor gene|url=https://www.ncbi.nlm.nih.gov/pubmed/12555067|journal=Oncogene|volume=22|issue=4|pages=538–547|doi=10.1038/sj.onc.1206141|issn=0950-9232|pmid=12555067}}</ref><ref>{{Cite journal|last=Rio-Machín|first=Ana|last2=Menezes|first2=Juliane|last3=Maiques-Diaz|first3=Alba|last4=Agirre|first4=Xabier|last5=Ferreira|first5=Bibiana I.|last6=Acquadro|first6=Francesco|last7=Rodriguez-Perales|first7=Sandra|last8=Juaristi|first8=Karmele A.|last9=Alvarez|first9=Sara|date=2012|title=Abrogation of RUNX1 gene expression in de novo myelodysplastic syndrome with t(4;21)(q21;q22)|url=https://www.ncbi.nlm.nih.gov/pubmed/22102704|journal=Haematologica|volume=97|issue=4|pages=534–537|doi=10.3324/haematol.2011.050567|issn=1592-8721|pmc=3347656|pmid=22102704}}</ref>.

The Runx1 protein has several functional domains (RDH, TAD and VWRPY) that interact with multiple proteins resulting in the control of expression of its target genes involved in hematopoietic differentiation, ribosome biogenesis, cell cycle regulation, and p53 and transforming growth factor β signaling pathways<ref name=":14" />. Various mutations have been reported resulting in loss of protein function including missense, nonsense, and framehshift changes which are distributed throughout the protein, particularly within the RHD domain<ref name=":14" />.

==Diagnostic Testing Methods==

Typically myeloid gene panel testing by massively parallel sequencing (Next Generation Sequencing) or targeted PCR assays that include the exons spanning the functional domains are used to detect ''RUNX1'' mutations.

==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==

AML patients with ''RUNX1'' mutation reportedly demonstrate reduced complete remission rate, poorer relapse-free survival, and poorer overall survival<ref name=":1" /><ref name=":4" /><ref name=":5" /><ref name=":6" /><ref name=":7" />. The NCCN guidelines (v.1.2018) state that ''RUNX1'' mutations have been associated with poor prognosis in AML, whereas 2017 European LeukemiaNet (ELN) recommendations for AML<ref name=":8" /><ref name=":9" /> have placed AML patients with mutated ''RUNX1'' in the absence of favorable risk markers in the adverse risk category. There are no therapies directly targeting inactivating alterations in ''RUNX1''. Preclinical studies suggest that ''RUNX1'' mutation may lead to the epigenetic repression of genes involved in apoptosis; treatment with DNA methyltransferase (''DNMT'') inhibitors may relieve this inhibition<ref name=":10" />. Co-occurrence of ''RUNX1'' and ''ASXL1'' mutation in AML patients has been linked to poor prognosis, including decreased response to induction therapy, increased risk of death, and decreased event-free and overall survival<ref name=":6" /><ref name=":11" /><ref name=":12" />. The presence of ''RUNX1'' mutation in combination with either ''PHF6'' or ''SRSF2'' mutation has been associated with poor prognosis, as compared with patients not harboring a co-mutation, in one study of 2439 newly diagnosed adult AML patients<ref name=":6" />.

==Familial Forms==

Familial platelet disorder with predisposition to acute myeloid leukemia (FPDMM) is a rare autosomal dominant disorder with thrombocytopenia, platelet dysfunction, bleeding propensity, and a significant risk of hematological malignancies, especially myelodysplastic syndromes and AML. Patients with this disorder have germline mutations in ''RUNX1''<ref name=":14" />.

==Other Information==

Not applicable.

==Links==

[[RUNX1]]

==References==
<references />

==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.

[[Category:Cancer Genes R]]
[[Category:Oncogenes R]]
[[Category:Recently Added Pages]]

HAEM4:Acute Myeloid Leukemia (AML) with Mutated RUNX1 - Revision history

Bailey.Glen at 21:27, 4 December 2023

Bailey.Glen at 18:45, 3 November 2023

Bailey.Glen: Created page with "==Primary Author(s)*== Iris Martin, M.D. Daynna J. Wolff, Ph.D. __TOC__ ==Cancer Category/Type== Acute Myeloid Leukemia ==Cancer Sub-Classification / Subtype== Acute My..."

Bailey.Glen: Created page with "==Primary Author(s)*== Iris Martin, M.D. Daynna J. Wolff, Ph.D. TOC ==Cancer Category/Type== Acute Myeloid Leukemia ==Cancer Sub-Classification / Subtype== Acute My..."