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'''Chromic Myeloid Leukemia (CML)'''
'''Chromic Myeloid Leukemia (CML)'''
A number of simple mutations have been reported in CML patients, and these mutations may be in part responsible for progression from the chronic phase to blast crisis (BC) (7).
'''Myelodysplastic Syndrome (MDS)'''
'''Myelodysplastic Syndrome (MDS)'''
A high frequency (42%) of AML1 mutations has been reported among radiation-associated and therapy-related Myelodysplastic Syndrome (MDS) patients (8).
'''CCUS or ICUS'''
'''CCUS or ICUS'''
'''Familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML)'''
'''Familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML)'''
Germ line mutations of RUNX1 have been reportedr in the rare autosomal dominant disease Familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML) (8).
==Gene Overview==
==Gene Overview==
The protein encoded by RUNX1 can bind the protein encoded by CBFB to form "Core Binding Factor", a hetero-dimeric transcription factor, which regulates a number of genes responsible for hematopoiesis and osteogenesis (2). Runx1 protein can bind to DNA as a monomer through the Runt domain within the Runx1 protein. The RUNX1 gene is the most frequent target for chromosomal translocation in leukemia (1). Alterations of RUNX1 are typically loss of function or decreased function, and are considered "secondary driver mutations" (disease progression) in sporadic leukemias (2), but germline RUNX1 mutations contribute a lifetime risk of myeloid malignancy of about 44% (2). RUNX1 mutations (loss of function or decreased function) have been associated with decreased P53 activity and increased DNA repair defects and increased inflammation (2).
The protein encoded by RUNX1 can bind the protein encoded by CBFB to form "Core Binding Factor", a hetero-dimeric transcription factor, which regulates a number of genes responsible for hematopoiesis and osteogenesis (2). Runx1 protein can bind to DNA as a monomer through the Runt domain within the Runx1 protein. The RUNX1 gene is the most frequent target for chromosomal translocation in leukemia (1). Alterations of RUNX1 are typically loss of function or decreased function, and are considered "secondary driver mutations" (disease progression) in sporadic leukemias (2), but germline RUNX1 mutations contribute a lifetime risk of myeloid malignancy of about 44% (2). RUNX1 mutations (loss of function or decreased function) have been associated with decreased P53 activity and increased DNA repair defects and increased inflammation (2). RUNX1 mutations are associated with gene mutations in ASXL1, MLLPTD, and IDH1/IDH2, but and are mutually exclusive with NPM1 mutations (3). Non-complex RUNX1 mutations were found to be associated with resistance to chemotherapy, and decreased disease free survival (DFS), event free survival (EFS) and overall survival (OS) (3). More importantly, RUNX1 mutations were deemed to be an independent prognostic marker for shorter EFS in multivariable analysis [62].
==Common Alteration Types==
==Common Alteration Types==
6. Taylor, J. et al. (2017). Diagnosis and classification of hematologic malignancies on the basis of genetics. Blood. 130:410-423. PMID 28600336 doi: 10.1182/blood-2017-02-734541
6. Taylor, J. et al. (2017). Diagnosis and classification of hematologic malignancies on the basis of genetics. Blood. 130:410-423. PMID 28600336 doi: 10.1182/blood-2017-02-734541
7. Zhao, LJ. et al. (2012). Functional features of RUNX1 mutants in acute transformation of chronic myeloid leukemia and their contribution to inducing murine full-blown leukemia. Blood 119: 2873-82. PMID: 22318203 DOI 10.1182/blood-2011-08-370981.
8. Harada H. et al. (2004). High incidence of somatic mutations in the AML1/RUNX1 gene in myelodysplastic syndrome and low blast percentage myeloid leukemia with myelodysplasia. Blood 103: 2316-24. PMID 14615365 DOI: 10.1182/blood-2003-09-3074
== Notes ==
== 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.
<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.