title: Blast crisis Ph+ chronic myeloid leukemia with NUP98/HOXA13 up-regulating MSI2.
abstract: BACKGROUND
  Musashi2(Msi2)-Numb pathway de-regulation is a molecular mechanism underlying the transition of chronic phase Ph + CML to deadly blast crisis, particularly in cases with a NUP98/HOXA9 fusion from a t(7;11)(p15;p15). This study provides new insights on the mechanisms cooperating in driving MSI2 over-expression and progression of Ph-positive CML.
  
  
  RESULTS
  Herein we describe a t(7;11)(p15;p15) originating a NUP98 fusion with HOXA13, at 7p15, in a 39 year-old man in blast crisis of Ph-positive CML. Both MSI2 and HOXA9 were evaluated by quantitative RT-PCR in our patient and in a series of haematological malignancies. Up-regulation of both genes emerged only in the presence of NUP98/HOXA13 gene fusion. However, over-expression of MSI2, but not HOXA9, was found in 2 cases of Ph + blast crisis with additional chromosome aberrations other than t(7;11). To determine the mechanisms underlying MSI2 over-expression in our patient we performed Chromatin Immunoprecipitation and found that NUP98/HOXA13 fusion protein deregulates MSI2 gene by binding its promoter.
  
  
  CONCLUSIONS
  To the best of our knowledge, this is the first molecular characterization of NUP98/HOXA13 fusion in blast crisis of Ph + CML. Our findings suggest cooperative mechanisms of MSI2 over-expression driven by HOXA proteins and strongly supports MSI2 as a prognostic marker and a candidate in target treatment of CML.
authors: Hematology and Bone Marrow Transplantation Unit, University of Perugia, Polo Unico S. Maria della Misericordia, Perugia, Italy.
authors: Danika
authors: D
authors: Di Giacomo
authors: Hematology and Bone Marrow Transplantation Unit, University of Perugia, Polo Unico S. Maria della Misericordia, Perugia, Italy.
authors: Valentina
authors: V
authors: Pierini
authors: Hematology and Bone Marrow Transplantation Unit, University of Perugia, Polo Unico S. Maria della Misericordia, Perugia, Italy.
authors: Gianluca
authors: G
authors: Barba
authors: Department of Internal Medicine, University of Perugia, Perugia, Italy.
authors: Veronica
authors: V
authors: Ceccarelli
authors: Department of Internal Medicine, University of Perugia, Perugia, Italy.
authors: Alba
authors: A
authors: Vecchini
authors: Hematology and Bone Marrow Transplantation Unit, University of Perugia, Polo Unico S. Maria della Misericordia, Perugia, Italy.
authors: Cristina
authors: C
authors: Mecucci
keywords: Blast crisis CML; Fusion transcript; HOXA genes; MSI2