Bailey.Glen at 18:43, 3 November 2023

2023-11-03T18:43:58Z

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 ==Primary Author(s)*==
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 <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)*== Fei Yang, MD, FACMG Oregon Health & Science University, Portland, OR TOC ==Cancer Category/Type== Myeloid Neoplasms with Germline Predispositio..."

2023-11-03T18:03:19Z

Created page with "==Primary Author(s)*== Fei Yang, MD, FACMG Oregon Health & Science University, Portland, OR __TOC__ ==Cancer Category/Type== Myeloid Neoplasms with Germline Predispositio..."

New page

==Primary Author(s)*==

Fei Yang, MD, FACMG

Oregon Health & Science University, Portland, OR

__TOC__

==Cancer Category/Type==

Myeloid Neoplasms with Germline Predisposition

==Cancer Sub-Classification / Subtype==

Myeloid Neoplasms with Germline ''ANKRD26'' Mutation

==Definition / Description of Disease==

This is a distinct entity in the World Health Organization (WHO) classification system within the section of [[Myeloid Neoplasms with Germline Predisposition]]<ref name=":0">Peterson LC, et al., (2017). Myeloid neoplasms with germline predisposition, 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, p125-126.</ref>.

This entity defines cases of myeloid neoplasms, in particular AML, MDS, and rarely CML and CMML, occur in association with inherited or ''de novo'' germline mutations in the ''ANKRD26'' gene.

==Synonyms / Terminology==

Thrombocytopenia 2; familial myeloid neoplasms with germline ''ANKRD26'' mutation; familial myelodysplastic syndromes/acute leukemias with germline ''ANKRD26'' mutation

==Epidemiology / Prevalence==

The median age of patients with onset of myeloid neoplasms is not well established. The prevalence of MDS/AML with germline ''ANKRD26'' mutations is currently unknown. There are about 45 affected pedigrees reported in the literature.

==Clinical Features==

Patients with germline ''ANKRD26'' mutation initially present with mild bleeding and thrombocytopenia at very variable age of onset<ref name=":3">{{Cite journal|displayauthors=1|last=Noris|first=Patrizia|last2=Perrotta|first2=Silverio|last3=Seri|first3=Marco|last4=Pecci|first4=Alessandro|last5=Gnan|first5=Chiara|last6=Loffredo|first6=Giuseppe|last7=Pujol-Moix|first7=Nuria|last8=Zecca|first8=Marco|last9=Scognamiglio|first9=Francesca|date=2011|title=Mutations in ANKRD26 are responsible for a frequent form of inherited thrombocytopenia: analysis of 78 patients from 21 families|url=https://pubmed.ncbi.nlm.nih.gov/21467542|journal=Blood|volume=117|issue=24|pages=6673–6680|doi=10.1182/blood-2011-02-336537|issn=1528-0020|pmid=21467542|via=}}</ref>. The common bleeding symptoms include petechiae, ecchymosis, gum bleeding, epistaxis, and menorrhagia<ref>{{Cite journal|displayauthors=1|last=Galera|first=Pallavi|last2=Dulau-Florea|first2=Alina|last3=Calvo|first3=Katherine R.|date=2019|title=Inherited thrombocytopenia and platelet disorders with germline predisposition to myeloid neoplasia|url=https://pubmed.ncbi.nlm.nih.gov/31069978|journal=International Journal of Laboratory Hematology|volume=41 Suppl 1|pages=131–141|doi=10.1111/ijlh.12999|issn=1751-553X|pmid=31069978|via=}}</ref>. The risk of developing myeloid neoplasms is estimated 30 times higher than that in the general population.

==Sites of Involvement==

Blood and bone marrow.

==Morphologic Features==

Patients with germline ''ANKRD26'' mutation who develop MDS/AML could show markedly hypercellular bone marrow, a high myeloid-to-erythroid ratio, prominent megakaryocytic atypia with an increased number of small hypolobated megakaryocytes, and erythroid and myeloid dysplasia<ref>{{Cite journal|last=Geyer|first=Julia T.|date=2019|title=Myeloid Neoplasms with Germline Predisposition|url=https://pubmed.ncbi.nlm.nih.gov/30048985|journal=Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology|volume=86|issue=1|pages=53–61|doi=10.1159/000490311|issn=1423-0291|pmid=30048985}}</ref>.

==Immunophenotype==

No typical immunophenotype is described in the current literature.

==Chromosomal Rearrangements (Gene Fusions)==

No typical chromosomal rearrangements/gene fusions are described in the current literature.
==Characteristic Chromosomal Aberrations / Patterns==

No typical chromosomal aberrations are described in the current literature. It could be non-specific alterations associated with MDS/AML.

==Genomic Gain/Loss/LOH==

No typical copy number aberrations are described in the current literature.
==Gene Mutations (SNV/INDEL)==

Most germline mutations in the ''ANKRD26'' gene are single nucleotide variants or small insertions/deletions occurring within the 5' untranslated region, resulting in the disruption of the assembly of RUNX1 and FLI1 on the ''ANKRD26'' promoter<ref name=":3" /><ref name=":2">{{Cite journal|displayauthors=1|last=Pippucci|first=Tommaso|last2=Savoia|first2=Anna|last3=Perrotta|first3=Silverio|last4=Pujol-Moix|first4=Núria|last5=Noris|first5=Patrizia|last6=Castegnaro|first6=Giovanni|last7=Pecci|first7=Alessandro|last8=Gnan|first8=Chiara|last9=Punzo|first9=Francesca|date=2011|title=Mutations in the 5' UTR of ANKRD26, the ankirin repeat domain 26 gene, cause an autosomal-dominant form of inherited thrombocytopenia, THC2|url=https://pubmed.ncbi.nlm.nih.gov/21211618|journal=American Journal of Human Genetics|volume=88|issue=1|pages=115–120|doi=10.1016/j.ajhg.2010.12.006|issn=1537-6605|pmc=3014357|pmid=21211618|via=}}</ref><ref>{{Cite journal|displayauthors=1|last=Marquez|first=Rafael|last2=Hantel|first2=Andrew|last3=Lorenz|first3=Rachelle|last4=Neistadt|first4=Barbara|last5=Wong|first5=Jerry|last6=Churpek|first6=Jane E.|last7=Mardini|first7=Nameer Al|last8=Shaukat|first8=Ismael|last9=Gurbuxani|first9=Sandeep|date=2014|title=A new family with a germline ANKRD26 mutation and predisposition to myeloid malignancies|url=https://pubmed.ncbi.nlm.nih.gov/24628296|journal=Leukemia & Lymphoma|volume=55|issue=12|pages=2945–2946|doi=10.3109/10428194.2014.903476|issn=1029-2403|pmc=4206674|pmid=24628296|via=}}</ref>. Truncating mutation in the N-terminus has also been reported<ref>{{Cite journal|displayauthors=1|last=Marconi|first=Caterina|last2=Canobbio|first2=Ilaria|last3=Bozzi|first3=Valeria|last4=Pippucci|first4=Tommaso|last5=Simonetti|first5=Giorgia|last6=Melazzini|first6=Federica|last7=Angori|first7=Silvia|last8=Martinelli|first8=Giovanni|last9=Saglio|first9=Giuseppe|date=2017|title=5'UTR point substitutions and N-terminal truncating mutations of ANKRD26 in acute myeloid leukemia|url=https://pubmed.ncbi.nlm.nih.gov/28100250|journal=Journal of Hematology & Oncology|volume=10|issue=1|pages=18|doi=10.1186/s13045-016-0382-y|issn=1756-8722|pmc=5242010|pmid=28100250|via=}}</ref>.
===Other Mutations===
Co-occurring somatic mutation in ''ASXL1'' has been reported in a patient with germline ''ANKRD26''-related thrombocytopenia and CMML<ref>{{Cite journal|displayauthors=1|last=Perez Botero|first=J.|last2=Oliveira|first2=J. L.|last3=Chen|first3=D.|last4=Reichard|first4=K. K.|last5=Viswanatha|first5=D. S.|last6=Nguyen|first6=P. L.|last7=Pruthi|first7=R. K.|last8=Majerus|first8=J.|last9=Gada|first9=P.|date=2015|title=ASXL1 mutated chronic myelomonocytic leukemia in a patient with familial thrombocytopenia secondary to germline mutation in ANKRD26|url=https://pubmed.ncbi.nlm.nih.gov/26001113|journal=Blood Cancer Journal|volume=5|pages=e315|doi=10.1038/bcj.2015.41|issn=2044-5385|pmc=4476020|pmid=26001113|via=}}</ref>.

==Epigenomics (Methylation)==

Not applicable.

==Genes and Main Pathways Involved==

The ''ANKRD26'' gene'','' located on the short arm of chromosome 10 (band 10p12.1), encodes a protein that plays a role in the TOP/MPL and MAPK/ERK pathways and is required for appropriate platelet formation and adipogenesis<ref name=":4">{{Cite journal|displayauthors=1|last=Bluteau|first=Dominique|last2=Balduini|first2=Alessandra|last3=Balayn|first3=Nathalie|last4=Currao|first4=Manuela|last5=Nurden|first5=Paquita|last6=Deswarte|first6=Caroline|last7=Leverger|first7=Guy|last8=Noris|first8=Patrizia|last9=Perrotta|first9=Silverio|date=2014|title=Thrombocytopenia-associated mutations in the ANKRD26 regulatory region induce MAPK hyperactivation|url=https://pubmed.ncbi.nlm.nih.gov/24430186|journal=The Journal of Clinical Investigation|volume=124|issue=2|pages=580–591|doi=10.1172/JCI71861|issn=1558-8238|pmc=3904625|pmid=24430186|via=}}</ref>. The ANKRD26 protein contains N-terminal ankyrin repeat domains and C-terminal spectrin helices. The exact cellular function of ANKRD26 and the molecular basis for the predisposition to myeloid malignancies is currently unknown. It is thought that gain-of-function mutations in ''ANKRD26'' result in increased gene transcription and signaling through the MPL pathway and impaired pro-platelet formation by megakaryocytes<ref name=":2" /><ref name=":4" />.

==Diagnostic Testing Methods==

Myeloid gene panel testing by Next generation sequencing, PCR, Sanger sequencing

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

The prognosis of myeloid neoplasms with germline ''ANKRD26'' mutation is currently not well established.

==Familial Forms==

''ANKRD26''-related thrombocytopenia (thrombocytopenia 2) is a rare autosomal dominant disorder characterized by lifelong mild-to-moderate thrombocytopenia with a normal platelet size, mild bleeding, no syndromic associations, and an increased risk of developing MDS/AML<ref name=":0" /><ref name=":1">Perez Botero J. et al. (2018). "ANKRD26-Related Thrombocytopenia" In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507664/.</ref>. The penetrance for thrombocytopenia is complete<ref name=":1" />.

==Other Information==

Not applicable.

==Links==

''[[ANKRD26]]''

==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 A]]
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HAEM4:Myeloid Neoplasms with Germline ANKRD26 Mutation - Revision history

Bailey.Glen at 18:43, 3 November 2023

Bailey.Glen: Created page with "==Primary Author(s)*== Fei Yang, MD, FACMG Oregon Health & Science University, Portland, OR __TOC__ ==Cancer Category/Type== Myeloid Neoplasms with Germline Predispositio..."

Bailey.Glen: Created page with "==Primary Author(s)*== Fei Yang, MD, FACMG Oregon Health & Science University, Portland, OR TOC ==Cancer Category/Type== Myeloid Neoplasms with Germline Predispositio..."