WCMC logo
PMKB
  • WCMC logoPMKB
  • Genes
  • Variants
  • Interpretations
  • Tumor Types
  • Primary Sites
  • Activity
  • Login
RUNX1
  • Information
  • View History
  • Pending Review
Interpretation 73
Tier 1
RUNX1
Variants
RUNX1 any mutation
Primary Sites
Blood
Bone Marrow
Tumor Types
Myelodysplastic Syndrome
Acute Myeloid Leukemia
Chronic Myelomonocytic Leukemia
T Lymphoblastic Leukemia/Lymphoma
Acute Leukemia of Unspecified Cell Type
Anemia, Unspecified
Atypical Chronic Myeloid Leukemia
B Lymphoblastic Leukemia/Lymphoma
Chronic Myeloid Leukemia
Chronic Neutrophilic Leukemia
Cytopenia
Eosinophilia
Essential Thrombocythemia
Histiocytic and Dendritic Cell Neoplasms
Langerhans Cell Histiocytosis
Leukocytosis
Leukopenia
Mast Cell Neoplasm
MDS with Ring Sideroblasts
Monocytosis
Myelodysplastic/Myeloproliferative Neoplasm
Myeloproliferative Neoplasm
Myeloid Neoplasm
Other Acute Leukemia
Polycythemia Vera
Polycythemia
Primary Myelofibrosis
Thrombocytopenia, Unspecified
Thrombocytosis
Interpretation

RUNX1(AML1, CBFA2) encodes the alpha subunit of core binding factor and is a transcription factor important in normal hematopoietic development. RUNX1 mutations have been reported in approximately 10% of myelodysplastic cases, 5-15% of acute myeloid leukemia, 8-37% of chronic myelomonocytic leukemia, 10% of T cell acute lymphoblastic leukemia, 3% of systemic mastocytosis, 2% of essential thrombocythemia and 2% of polycythemia vera. The mutations include frameshift, missense, nonsense, and splice site mutations. Typically, the Runt domain and the region just downstream of the Runt domain are affected and the mutations tend to be monoallelic. AML with RUNX1 mutation which does not fulfill the diagnostic criteria for other specific AML subtypes in the categories of AML with recurrent genetic abnormalities, therapy-related myeloid neoplasms, or AML with myelodysplasia-related changes is now classified the provisional entity of AML with mutated RUNX1. RUNX1 mutations may be associated with Trisomy 8 or MLL-PTD in AML according to some studies. They tend not to occur in AML cases with favorable cytogenetic findings and appear to be exclusive of NPM1 or CEBPA mutations in AML. Myeloid neoplasms, predominantly MDS/AML, developing in patients, usually at a young age, with a familial platelet disorder and germline monoallelic RUNX1 mutations are categorized as myeloid neoplasms with germline RUNX1 mutation. Of note, RUNX1 may also be involved in large intragenic deletions and translocations (e.g., t(8;21)(RUNX1-ETO), t(3;21)(RUNX1-EVI1), t(12;21)(TEL-RUNX1) which are not detected by this assay. Mutated RUNX1 is a poor-risk prognostic marker in AML unless it co-occurs with favorable-risk AML subtypes (NCCN Guidelines for AML). RUNX1 nonsense or frameshift mutations are associated with an unfavorable prognosis in myelodysplastic syndrome, independent of IPSS, IPSS-R, age, and other gene mutations (NCCN Guidelines for Myelodysplastic Syndromes). RUNX1 mutations are independently associated with unfavorable outcomes and shorter survival after hematopoietic stem cell transplantation in patients with myelodysplastic syndrome and myelodysplastic syndrome/acute myeloid leukemia. RUNX1 mutations are also associated with an unfavorable prognosis chronic myelomonocytic leukemia and systemic mastocytosis.

Citations
  1. Bejar R, et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med 2011;364(26):2496-506
  2. Mangan JK, et al. RUNX1 mutations in clonal myeloid disorders: from conventional cytogenetics to next generation sequencing, a story 40 years in the making. Crit Rev Oncog 2011;16(1-2):77-91
  3. Kihara R, et al. Comprehensive analysis of genetic alterations and their prognostic impacts in adult acute myeloid leukemia patients. Leukemia 2014;28(8):1586-95
  4. Haferlach T, et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia 2014;28(2):241-7
  5. Ichikawa M, et al. A role for RUNX1 in hematopoiesis and myeloid leukemia. Int J Hematol 2013;97(6):726-34
  6. Cazzola M, et al. The genetic basis of myelodysplasia and its clinical relevance. Blood 2013;122(25):4021-34
  7. Mok MM, et al. RUNX1 point mutations potentially identify a subset of early immature T-cell acute lymphoblastic leukaemia that may originate from differentiated T-cells. Gene 2014;545(1):111-6
  8. Zhang J, et al. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature 2012;481(7380):157-63
  9. Metzeler KH, et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood 2016;128(5):686-98
  10. Elena C, et al. Integrating clinical features and genetic lesions in the risk assessment of patients with chronic myelomonocytic leukemia. Blood 2016;128(10):1408-17
  11. Pardanani A, et al. Next-generation sequencing in systemic mastocytosis: Derivation of a mutation-augmented clinical prognostic model for survival. Am J Hematol 2016;91(9):888-93
  12. Arber DA, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016;127(20):2391-405
  13. Della Porta MG, et al. Clinical Effects of Driver Somatic Mutations on the Outcomes of Patients With Myelodysplastic Syndromes Treated With Allogeneic Hematopoietic Stem-Cell Transplantation. J Clin Oncol 2016;34(30):3627-3637
  14. Metzeler KH, et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood 2016;128(5):686-98
  15. Elena C, et al. Integrating clinical features and genetic lesions in the risk assessment of patients with chronic myelomonocytic leukemia. Blood 2016;128(10):1408-17
  16. Pardanani A, et al. Next-generation sequencing in systemic mastocytosis: Derivation of a mutation-augmented clinical prognostic model for survival. Am J Hematol 2016;91(9):888-93
  17. Tefferi A, et al. Targeted deep sequencing in polycythemia vera and essential thrombocythemia. Blood Adv 2016;1(1):21-30
Last updated: 2019-08-28 14:54:01 UTC
PMKB Bot
  • Genes
  • Variants
  • Interpretations
  • Tumor Types
  • Primary Sites
  • Activity

Disclaimer: You assume full responsibility for all risks associated with using this PMKB website. The Englander Institute for Precision Medicine at Weill Cornell Medicine makes no guarantee of the comprehensiveness, reliability or accuracy of the information on this website and assumes no responsibility for errors in the information associated with this web site. Healthcare providers and patients must integrate all clinical and laboratory findings as well as information from a variety of sources before deciding on appropriate clinical care options.


When using PMKB, please cite: Huang et al., JAMIA 2017


HELP
User Guide
Video Tutorial
INFO
About
Latest
API
Twitter
CONTACT US
Contact

Englander Institute for Precision Medicine
© Weill Cornell Medicine | Version 1.7.2Privacy PolicyTerms of use