The protein encoded by RUNX1 is a
transcription factor associated with acute myeloid leukemia (AML). It belongs
to the Runt-related transcription factor (RUNX) family of genes which are also
called core binding factor-α (CBFα). RUNX proteins form a heterodimeric complex
with CBFβ which confers increased DNA binding and stability to the complex. RUNX1
is thought to be involved in the development of normal hematopoiesis.
Somatic RUNX1 mutations (deletion,
insertion, point mutations) have been observed in tumors of
haematopoietic/lymphoid tissue and CNS.There are no mutational hot spots.
RUNX1 is frequently mutated in sporadic
myeloid and lymphoid leukemia through translocation, point mutation or
amplification. It is also responsible for a familial platelet disorder with
predisposition to acute myeloid leukemia (FPD-AML).
Chromosomal alterations involving RUNX1
and leading to fusion genes are well-documented and have been associated with
several types of leukemia.
ins(8;21)(q22;q22q22) leads to RUNX1-RUNX1T1
ins(21;8)(q22;q13q22) leads to
RUNX1-RUNX1T1 in AML
ins(21;8)(q22;q21q22) leads to RUNX1-RUNX1T1
t(1;21)(p35;q22) leads to RUNX1-YTHDF2 in AML
t(1;21)(p36;q22) leads to RUNX1-PRDM16 in AMLt,
t(1;21)(q21;q22) leads to RUNX1-ZNF687 in AML
t(2;21)(q11;q22) leads to RUNX1-AFF3 in T-ALL
t(3;21)(q26;q22) leads to RUNX1-RPL22P1 in
CML, AML, MDS
t(3;21)(q26;q22) leads to RUNX1-MDS1 in AMLt,
t(3;21)(q26;q22) leads to RUNX1-EVI1 in CML,
MDSt, AML, AMLt
t(4;21)(q31;q22) leads to RUNX1-SH3D19 in AML
t(7;21)(p22;q22) leads to RUNX1-USP42 in AML
t(8;21)(q21-q22;q22) leads to RUNX1-RUNX1T1 in AML
t(8;21)(q23;q22) leads to ZFPM2-RUNX1 in
t(8;21)(q24;q22) leads to RUNX1-TRPS1 in T-ALL,
t(11;21)(q13;q22) leads to MACROD1-RUNX in
AML, CML, MDS
t(12;21)(p13;q22) leads to ETV6-RUNX1in B-ALL
t(12;21)(q12;q22) leads to RUNX1-CPNE8 in
t(16;21)(q24;q22) leads to RUNX1-CBFA2T3
in MDS, AML, AMLt
RUNX1 genetic alterations are the cause of
familial platelet disorder with associated myeloid malignancy (FPD-AML or FPDMM),
which is an autosomal dominant disease characterized by qualitative and
quantitative platelet defects, and propensity to develop acute myelogenous
References (open access) :
Familial myelodysplastic syndromes - a review of the literature. Liew E,
Owen CJ. Haematologica. 2011 May 23
Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1,
NRAS, RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid
leukemias. Rocquain J, Carbuccia N, Trouplin V, Raynaud S, Murati A, Nezri M,
Tadrist Z, Olschwang S, Vey N, Birnbaum D, Gelsi-Boyer V, Mozziconacci MJ. BMC
Cancer. 2010 Aug 2;10:401.
RUNX1 regulates phosphoinositide 3-kinase/AKT pathway: role in
chemotherapy sensitivity in acute megakaryocytic leukemia. Edwards H, Xie C,
LaFiura KM, Dombkowski AA, Buck SA, Boerner JL, Taub JW, Matherly LH, Ge Y. Blood.
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