title: FOXP1 and TP63 involvement in the progression of myelodysplastic syndrome with 5q- and additional cytogenetic abnormalities.
abstract: BACKGROUND
  The progression of low-risk del(5q) myelodysplastic syndrome to acute myeloid leukemia is increased when associated with mutations of TP53, or with additional chromosomal abnormalities. However, to date the prognostic impact and molecular consequences of these rearrangements were poorly investigated. Single additional alterations to del(5q) by balanced chromosome rearrangements were rarely found in myelodysplasia. In particular, balanced alterations involving TP63 and FOXP1 genes were never reported in the literature.
  
  
  METHODS
  Here we report on a 79-year woman with an aggressive form of myelodysplastic syndrome with del(5q), no TP53 mutation, and a novel complex rearrangement of chromosome 3 in bone marrow cells. Our results revealed that the FOXP1 and TP63 genes were both relocated along chromosome 3. Strikingly, immunohistochemistry analysis showed altered protein levels, disclosing that this rearrangement triggered the expression of FOXP1 and TP63 genes. FOXP1 was also found activated in other patients with myelodysplasia and acute myeloid leukemia, showing that it is an important, recurrent event.
  
  
  CONCLUSIONS
  We document an apparent role of FOXP1 and TP63, up to now poorly documented, in the progression of MDS in our patient who is lacking mutations in the TP53 tumor suppressor gene normally associated with poor outcome in myelodysplastic syndrome with 5q-. Finally, our results may suggest a possible broader role of FOXP1 in the pathogenesis and progression of myelodysplasia and acute myeloid leukemia.
authors.forename: Alberto
authors.initials: A
authors.lastname: L'Abbate
authors.forename: Crocifissa
authors.initials: C
authors.lastname: Lo Cunsolo
authors.forename: Ettore
authors.initials: E
authors.lastname: Macrì
authors.forename: Paolo
authors.initials: P
authors.lastname: Iuzzolino
authors.forename: Cristina
authors.initials: C
authors.lastname: Mecucci
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.forename: Michelina
authors.initials: M
authors.lastname: Coco
authors.forename: Lucia Anna
authors.initials: LA
authors.lastname: Muscarella
authors.forename: Simona
authors.initials: S
authors.lastname: Salati
authors.forename: Enrico
authors.initials: E
authors.lastname: Tagliafico
authors.forename: Carla
authors.initials: C
authors.lastname: Minoia
authors.forename: Giacoma
authors.initials: G
authors.lastname: De Tullio
authors.forename: Attilio
authors.initials: A
authors.lastname: Guarini
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Testoni
authors.forename: Claudio
authors.initials: C
authors.lastname: Agostinelli
authors.affiliation: Department of Biology, University of Bari, Via G,Amendola 165/A, Bari 70126, Italy. cleliatiziana.storlazzi@uniba.it.
authors.forename: Clelia Tiziana
authors.initials: CT
authors.lastname: Storlazzi
mesh_terms: D000368:Aged; D002869:Chromosome Aberrations; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D018450:Disease Progression; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D012097:Repressor Proteins; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins