• What is U2AF1?
  • U2AF1 in Myelodysplastic Syndromes
  • U2AF1 Mutations
  • Clinical Trials

U2AF1

U2 small nuclear RNA auxiliary factor 1 (U2AF1) is a gene that encodes for a member of the spliceosome. The protein coded by this gene is part of the U2 auxiliary factor, which plays an important role in RNA splicing (Gene 2014). Spliceosome mutations are observed in MDS, chronic lymphocytic leukemia (CLL), AML, and chronic myelomonocytic leukemia (CMML), and these mutations can cause abnormal expression patterns of some genes involved in cancer pathogenesis (Chesnais et al. 2012).​

Related Pathways

Contributors: Stephen A. Strickland, M.D., MSCI, Annette S. Kim, M.D., Ph.D.

Suggested Citation: Strickland, S., A. Kim. 2015. U2AF1. My Cancer Genome https://www.padiracinnovation.org/content/disease/myelodysplastic-syndromes/u2af1/?tab=0 (Updated December 7).

Last Updated: December 7, 2015

U2AF1 in Myelodysplastic Syndromes

U2AF1 mutations occur in 6.2% of MDS (COSMIC). U2AF1 mutations are most often observed in refractory cytopenia with multilineage dysplasia (RCMD) and refractory anemia with excess blasts (RAEB), two subtypes of high risk MDS (Cazzola, Della Porta, and Malcovati 2013). The role of U2AF1 mutations in MDS is not yet well understood (Visconte et al. 2012​). U2AF1 mutations are localized in the zinc finger domains, in particular amino acids A26, S34, and Q157, suggesting aberrations in the nucleic acid recognition function of the protein.

U2AF1 mutations have been associated with less favorable overall survival and a higher likelihood of transformation to AML (Cazzola, Della Porta, and Malcovati 2013; Graubert et al. 2011; Makishima et al. 2012).​

Contributors: Stephen A. Strickland, M.D., MSCI, Annette S. Kim, M.D., Ph.D.

Suggested Citation: Strickland, S., A. Kim. 2014. U2AF1 in Myelodysplastic Syndromes. My Cancer Genome https://www.padiracinnovation.org/content/disease/myelodysplastic-syndromes/u2af1/ (Updated September 23).

Last Updated: September 23, 2014

U2AF1 Mutations in Myelodysplastic Syndromes

Properties
Location of mutations U2AF1 gene on 21q22.3
Frequency of U2AF1 mutations in MDS 6.2% (COSMIC)
Implications for Targeted Therapeutics
Response to bromodomain inhibitors, DOT1L inhibitors, or other targeted epigenetic therapies Unknown at this timea
Response to spliceosome-targeting therapies Unknown at this timeb
Response to Ras-targeting therapies Unknown at this timec

The most frequently mutated positions of U2AF1 are S34 (60.8%; COSMIC) and Q157 (28.5%; COSMIC). U2AF1 mutations have been associated with less favorable overall survival and a higher likelihood of transformation to AML (Cazzola, Della Porta, and Malcovati 2013; Graubert et al. 2011; Makishima et al. 2012).

a Bromodomain (BRD2, BRD3, BRD4, and BRDt) inhibitors and DOT1L inhibitors are in phase I studies in hematologic malignancies (Abdel-Wahab and Levine 2013). In addition, several other epigenetic targeted therapies, targeting IDH1/IDH2, EZH2, LSD1, or UTX/JMJD3, are in development (Abdel-Wahab and Levine 2013).

b Drugs targeting the spliceosome are in development; these drugs alter gene expression or affect alternative splicing in ways that inhibit cancer progression (Bonnal, Vigevani, and Valcarcel 2012).

c Efforts to develop Ras-targeting therapies are in progress and are hoped to be useful in hematologic malignancies (Ward, Braun, and Shannon 2012).

Contributors: Stephen A. Strickland, M.D., MSCI, Annette S. Kim, M.D., Ph.D.

Suggested Citation: Strickland, S., A. Kim. 2014. U2AF1 Mutations in Myelodysplastic Syndromes. My Cancer Genome https://www.padiracinnovation.org/content/disease/myelodysplastic-syndromes/u2af1/332/ (Updated September 23).

Last Updated: September 23, 2014

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