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Roberta La Starza,
Barbara Crescenzi,
Valeria Nofrini,
Gianluca Barba,
Caterina Matteucci,
Lucia Brandimarte,
Valentina Pierini,
Nicoletta Testoni,
Pellegrino Musto,
Stefania Paolini,
Valentina Gianfelici,
Clelia T Storlazzi,
Antonio Pierini, Laura Berchicci,
Paolo Gorello,
Cristina Mecucci
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[hide abstract]
ABSTRACT: We investigated TET2 deletion in 418 patients with hematological malignancies. Overall interphase FISH detected complete or partial TET2 monoallelic deletion (TET2(del)) in 20/418 cases (4.7%). TET2(del) was very rare in lymphoid malignancies (1/242 cases; 0.4%). Among 19 positive myeloid malignancies TET2(del) was associated with a 4q24 karyotypic abnormality in 18 cases. In AML, TET2(del) occurred in CD34-positive hematopoietic precursors and preceded established genomic abnormalities, such as 5q- and -7/7q-, which were the most frequent associated changes (Fisher's exact test P=0.000).
Leukemia research 09/2011; 36(1):37-41. · 2.36 Impact Factor
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Valeria Nofrini, Laura Berchicci,
Roberta La Starza,
Paolo Gorello,
Danika Di Giacomo,
Francesco Arcioni,
Valentina Pierini,
Barbara Crescenzi,
Silvia Romoli,
Caterina Matteucci,
Cristina Mecucci
Leukemia research 07/2011; 35(7):e123-6. · 2.36 Impact Factor
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Roberta La Starza,
Caterina Matteucci,
Paolo Gorello,
Lucia Brandimarte,
Valentina Pierini,
Barbara Crescenzi,
Valeria Nofrini,
Roberto Rosati,
Enrico Gottardi,
Giuseppe Saglio,
Antonella Santucci, Laura Berchicci,
Francesco Arcioni,
Brunangelo Falini,
Massimo Fabrizio Martelli,
Constantina Sambani,
Anna Aventin,
Cristina Mecucci
[show abstract]
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ABSTRACT: NPM1 gene at chromosome 5q35 is involved in recurrent translocations in leukemia and lymphoma. It also undergoes mutations in 60% of adult acute myeloid leukemia (AML) cases with normal karyotype. The incidence and significance of NPM1 deletion in human leukemia have not been elucidated.
Bone marrow samples from 145 patients with myelodysplastic syndromes (MDS) and AML were included in this study. Cytogenetically 43 cases had isolated 5q-, 84 cases had 5q- plus other changes and 18 cases had complex karyotype without 5q deletion. FISH and direct sequencing investigated the NPM1 gene. NPM1 deletion was an uncommon event in the "5q- syndrome" but occurred in over 40% of cases with high risk MDS/AML with complex karyotypes and 5q loss. It originated from large 5q chromosome deletions. Simultaneous exon 12 mutations were never found. NPM1 gene status was related to the pattern of complex cytogenetic aberrations. NPM1 haploinsufficiency was significantly associated with monosomies (p<0.001) and gross chromosomal rearrangements, i.e., markers, rings, and double minutes (p<0.001), while NPM1 disomy was associated with structural changes (p=0.013). Interestingly, in complex karyotypes with 5q- TP53 deletion and/or mutations are not specifically associated with NPM1 deletion.
NPM1/5q35 deletion is a consistent event in MDS/AML with a 5q-/-5 in complex karyotypes. NPM1 deletion and NPM1 exon 12 mutations appear to be mutually exclusive and are associated with two distinct cytogenetic subsets of MDS and AML.
PLoS ONE 01/2010; 5(9):e12855. · 4.09 Impact Factor
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Roberta La Starza,
Lucia Brandimarte,
Valentina Pierini,
Valeria Nofrini,
Paolo Gorello,
Barbara Crescenzi, Laura Berchicci,
Caterina Matteucci,
Silvia Romoli,
Donatella Beacci,
Roberto Rosati,
Massimo F Martelli,
Cristina Mecucci
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ABSTRACT: We report a case of adult acute myeloid leukemia with a new t(11;12)(p15;q13) underlying a NUP98 rearrangement without HOXC cluster gene involvement. We designed a specific double-color double-fusion FISH assay to discriminate between this t(11;12)(p15;q13) and those producing NUP98-HOXC11 or NUP98-HOXC13. Our fluorescence in situ hybridization (FISH) showed that putative candidate partners mapping 600 kilobases centromeric to HOXC were RARG (retinoic acid receptor gamma), MFSD5 (major facilitator superfamily domain containing 5), and ESPL1 (extra spindle pole bodies homolog 1). It is noteworthy that so far only ESPL1 has been implicated in human cancers. This FISH assay is useful for diagnostic screening of NUP98-positive leukemias.
Cancer genetics and cytogenetics 10/2009; 193(2):109-11. · 1.54 Impact Factor
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[show abstract]
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ABSTRACT: A 68-year-old man diagnosed with primary plasma-cell leukemia was given thalidomide maintenance treatment for his disease. He had previously failed induction therapy with cyclophosphamide, vincristine, adriamycin, and dexamethasone, but achieved complete remission after melphalan therapy. Multiple syncopal episodes started to occur during thalidomide treatment, and a Holter electrocardiogram showed multiple abnormalities, with an episode of sustained ventricular tachycardia.
Blood tests, peripheral blood smear, bone-marrow biopsy and aspirate, Holter electrocardiogram.
Sustained ventricular tachycardia possibly owing to thalidomide treatment.
Thalidomide withdrawal, dexamethasone maintenance therapy, monthly oral courses of combined melphalan and prednisone, salvage therapy with bortezomib.
Nature Clinical Practice Oncology 01/2008; 4(12):722-5. · 8.00 Impact Factor
