FOXP1 and TP63 involvement in the progression of myelodysplastic syndrome with 5q- and additional cytogenetic abnormalities
1 Department of Biology, University of Bari, Via G.Amendola 165/A, Bari 70126, Italy
2 UO Anatomia Patologica, Ospedale S. Martino, Belluno, Italy
3 Hematology Unit, University of Perugia, Polo Unico S.M. Misericordia, Perugia, Italy
4 Istituto Scientifico San Raffaele, Milan, Italy
5 Laboratory of Oncology, IRCCS “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Italy
6 Center for Genome Research, Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy
7 Haematology Unit, Department of Medical and Experimental Oncology, IRCCS National Cancer Research Centre “Giovanni Paolo II”, Bari, Italy
8 “Seràgnoli” Institute of Hematology, Bologna University School of Medicine, Bologna, Italy
BMC Cancer 2014, 14:396 doi:10.1186/1471-2407-14-396Published: 3 June 2014
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.
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.
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.