FOXP1 and TP63 involvement in the progression of myelodysplastic syndrome with 5q- and additional cytogenetic abnormalities

Alberto L'Abbate, Crocifissa Lo Cunsolo, Ettore Macrì, Paolo Iuzzolino, Cristina Mecucci, Claudio Doglioni, Michelina Coco, Lucia A. Muscarella, Simona Salati, Enrico Tagliafico, Carla Minoia, Giacoma De Tullio, Attilio Guarini, Nicoletta Testoni, Claudio Agostinelli, Clelia T. Storlazzi

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.Case presentation: 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.

Original languageEnglish
Article number396
JournalBMC Cancer
Volume14
Issue number1
DOIs
Publication statusPublished - Jun 3 2014

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Myelodysplastic Syndromes
Acute Myeloid Leukemia
Chromosome Aberrations
Chromosomes, Human, Pair 3
Mutation
Genes
Tumor Suppressor Genes
Bone Marrow Cells
Chromosomes
Immunohistochemistry
Proteins

Keywords

  • Chromosome 3
  • Double inversion
  • Gene activation
  • Myeloid leukemia
  • TP53

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics
  • Medicine(all)

Cite this

FOXP1 and TP63 involvement in the progression of myelodysplastic syndrome with 5q- and additional cytogenetic abnormalities. / L'Abbate, Alberto; Lo Cunsolo, Crocifissa; Macrì, Ettore; Iuzzolino, Paolo; Mecucci, Cristina; Doglioni, Claudio; Coco, Michelina; Muscarella, Lucia A.; Salati, Simona; Tagliafico, Enrico; Minoia, Carla; De Tullio, Giacoma; Guarini, Attilio; Testoni, Nicoletta; Agostinelli, Claudio; Storlazzi, Clelia T.

In: BMC Cancer, Vol. 14, No. 1, 396, 03.06.2014.

Research output: Contribution to journalArticle

L'Abbate, A, Lo Cunsolo, C, Macrì, E, Iuzzolino, P, Mecucci, C, Doglioni, C, Coco, M, Muscarella, LA, Salati, S, Tagliafico, E, Minoia, C, De Tullio, G, Guarini, A, Testoni, N, Agostinelli, C & Storlazzi, CT 2014, 'FOXP1 and TP63 involvement in the progression of myelodysplastic syndrome with 5q- and additional cytogenetic abnormalities', BMC Cancer, vol. 14, no. 1, 396. https://doi.org/10.1186/1471-2407-14-396
L'Abbate, Alberto ; Lo Cunsolo, Crocifissa ; Macrì, Ettore ; Iuzzolino, Paolo ; Mecucci, Cristina ; Doglioni, Claudio ; Coco, Michelina ; Muscarella, Lucia A. ; Salati, Simona ; Tagliafico, Enrico ; Minoia, Carla ; De Tullio, Giacoma ; Guarini, Attilio ; Testoni, Nicoletta ; Agostinelli, Claudio ; Storlazzi, Clelia T. / FOXP1 and TP63 involvement in the progression of myelodysplastic syndrome with 5q- and additional cytogenetic abnormalities. In: BMC Cancer. 2014 ; Vol. 14, No. 1.
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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.Case presentation: 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.",
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AU - L'Abbate, Alberto

AU - Lo Cunsolo, Crocifissa

AU - Macrì, Ettore

AU - Iuzzolino, Paolo

AU - Mecucci, Cristina

AU - Doglioni, Claudio

AU - Coco, Michelina

AU - Muscarella, Lucia A.

AU - Salati, Simona

AU - Tagliafico, Enrico

AU - Minoia, Carla

AU - De Tullio, Giacoma

AU - Guarini, Attilio

AU - Testoni, Nicoletta

AU - Agostinelli, Claudio

AU - Storlazzi, Clelia T.

PY - 2014/6/3

Y1 - 2014/6/3

N2 - 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.Case presentation: 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.

AB - 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.Case presentation: 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.

KW - Chromosome 3

KW - Double inversion

KW - Gene activation

KW - Myeloid leukemia

KW - TP53

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