Not Logged In

NOTCH2 and FLT3 gene mis-splicing are common events in patients with acute myeloid leukemia (AML): new potential targets in AML

Our previous studies revealed an increase in alternative splicing of multiple RNAs in cells from patients with acute myeloid leukemia (AML) compared with CD34+ bone marrow cells from normal donors. Aberrantly spliced genes included a number of oncogenes, tumor suppressor genes, and genes involved in regulation of apoptosis, cell cycle, and cell differentiation. Among the most commonly mis-spliced genes (>70% of AML patients) were 2, NOTCH2 and FLT3, that encode myeloid cell surface proteins. The splice variants of NOTCH2 and FLT3 resulted from complete or partial exon skipping and utilization of cryptic splice sites. Longitudinal analyses suggested that NOTCH2 and FLT3 aberrant splicing correlated with disease status. Correlation analyses between splice variants of these genes and clinical features of patients showed an association between NOTCH2-Va splice variant and overall survival of patients. Our results suggest that NOTCH2 and FLT3 mis-splicing is a common characteristic of AML and has the potential to generate transcripts encoding proteins with altered function. Thus, splice variants of these genes might provide disease markers and targets for novel therapeutics.

Citation

S. Adamia, M. Bar-Natan, B. Haibe-Kains, P. Pilarski, C. Bach, S. Pevzner, T. Calimeri, H. Avet-Loiseau, L. Lode, S. Verselis, E. Fox, I. Galinsky, S. Mathews, I. Dagogo-Jack, M. Wadleigh, D. Steensma, G. Motyckova, D. Deangelo, J. Quackenbush, D. Tenen, R. Stone, J. Griffin. "NOTCH2 and FLT3 gene mis-splicing are common events in patients with acute myeloid leukemia (AML): new potential targets in AML". Blood, 123(18), pp 2816–2825, May 2014.

Keywords: flt3 gene, leukemia, myelocytic, acute, ms-like tyrosine kinase 3, rna splicing, genes
Category: In Journal
Web Links: doi

BibTeX

@article{Adamia+al:14,
  author = {Sophia Adamia and Michal Bar-Natan and Benjamin Haibe-Kains and
    Patrick M. Pilarski and Christian Bach and Samuel Pevzner and Teresa
    Calimeri and Herve Avet-Loiseau and Laurence Lode and Sigitas Verselis and
    Edward A. Fox and Ilene Galinsky and Steven Mathews and Ibiayi Dagogo-Jack
    and Martha Wadleigh and David P. Steensma and Gabriela Motyckova and Daniel
    J. Deangelo and John Quackenbush and Daniel G. Tenen and Richard M. Stone
    and James D. Griffin},
  title = {NOTCH2 and FLT3 gene mis-splicing are common events in patients with
    acute myeloid leukemia (AML): new potential targets in AML},
  Volume = "123",
  Number = "18",
  Pages = {2816–2825},
  journal = {Blood},
  year = 2014,
}

Last Updated: November 10, 2020
Submitted by Sabina P

University of Alberta Logo AICML Logo