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Acute Myeloid Leukemia (AML);
Acute Myeloid Leukemia (AML);
The most common chromosomal translocations is t(8;21)(q22;q22) in de novo AML (2) RUNX1-RUNX1T1. translocations confer a favorable prognosis in their respective diseases (2)
inv(16)(p13;q22) or t(16)(p13;q22), which disrupt CBFB the non-DNA-binding partner of RUNX1: also translocation confer a favorable prognosis in their respective diseases (2)
Mono- and biallelic mutations in RUNX1 include deletions, missense, splicing, frameshift, and nonsense mutations. These mutations are mechanistically distinct from the chromosomal translocations and confer a worse prognosis (2)
T-cell Acute Lymphocytic Leukemia (B-ALL)
B-cell Acute Lymphocytic Leukemia (B-ALL) most common chromosomal translocations is t(12;21)(p13;q22) in acute lymphocytic leukemia (B-ALL) (2) ETV6-RUNX1. translocation confer a favorable prognosis in their respective diseases(2)
Chromic Myeloid Leukemia (CML)
Chromic Myeloid Leukemia (CML)
Myelodysplastic Syndrome (MDS)
CCUS or ICUS
RUNX1 mutations are more common in clonal cytopenia of undetermined significance (CCUS) (2)
Familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML)
==Gene Overview==
==Gene Overview==
The protein encoded by RUNX1 can bind the protein encoded by CBFB to form "Core Binding Factor", a heterodimeric transcription factor, which can bind to DNA as a monomer and through the Runt domain within the Runx1 protein. Chromosomal translocations involving this gene are well-documented and have been associated with several types of leukemia.
The protein encoded by RUNX1 can bind the protein encoded by CBFB to form "Core Binding Factor", a hetero-dimeric transcription factor, which can bind to DNA as a monomer and through the Runt domain within the Runx1 protein. Runx1 protein is essential for hemopoietic stem cell formation and is important for the differentiation of lymphoid, myeloid and megakaryocytic cell lineages (2). Chromosomal translocations involving this gene are well-documented and have been associated with several types of leukemia. Alterations of RUNX1 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 (2).
==Common Alteration Types==
==Common Alteration Types==
! Copy Number Loss !! Copy Number Gain !! LOH !! Loss-of-Function Mutation !! Gain-of-Function Mutation !! Translocation/Fusion
! Copy Number Loss !! Copy Number Gain !! LOH !! Loss-of-Function Mutation !! Gain-of-Function Mutation !! Translocation/Fusion
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| EXAMPLE: X ||EXAMPLE: X || EXAMPLE: X || EXAMPLE: X || EXAMPLE: X || EXAMPLE: X
| EXAMPLE: ||EXAMPLE: || EXAMPLE: || EXAMPLE: X || EXAMPLE: || EXAMPLE: X
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