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Mariam Ibáñez,
Esperanza Such,
José Cervera,
Irene Luna,
Inés Gómez-Seguí,
María López-Pavía,
Sandra Dolz,
Eva Barragán,
Oscar Fuster,
Marta Llop,
Rebeca Rodríguez-Veiga,
Amparo Avaria,
Silvestre Oltra,
M Leonor Senent,
Federico Moscardó,
Pau Montesinos,
David Martínez-Cuadrón,
Guillermo Martín,
Miguel A Sanz
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ABSTRACT: Recently, many novel molecular abnormalities were found to be distinctly associated with acute myeloid leukemia (AML). However, their clinical relevance and prognostic implications are not well established. We developed a new combination of high-resolution melting assays on a LightCycler 480 and direct sequencing to detect somatic mutations of ASXL1 (exon 12), IDH1 (exon 4), IDH2 (exon 4), and c-CBL (exons 8 and 9) genes to know their incidence and prognostic effect in a cohort of 175 patients with de novo AML: 16 patients (9%) carried ASXL1 mutations, 16 patients had IDH variations (3% with IDH1(R132) and 6% with IDH2(R140)), and none had c-CBL mutations. Patients with ASXL1 mutations did not harbor IDH1, FLT3, or CEBPA mutations, and a combination of ASXL1 and IDH2 mutations was found only in one patient. In addition, we did not find IDH1 and FLT3 or CEBPA mutations concurrently or IDH2 with CEBPA. IDH1 and IDH2 mutations were mutually exclusive. Alternatively, NPM1 mutations were concurrently found with ASXL1, IDH1, or IDH2 with a variable incidence. Mutations were not significantly correlated with any of the clinical and biological features studied. High-resolution melting is a reliable, rapid, and efficient screening technique for mutation detection in AML. The incidence for the studied genes was in the range of those previously reported. We were unable to find an effect on the outcome.
The Journal of molecular diagnostics: JMD 08/2012; 14(6):594-601. · 3.48 Impact Factor
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Leukemia & lymphoma 08/2012; · 2.40 Impact Factor
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Esperanza Such,
José Cervera,
Evangelos Terpos,
José V Bagán,
Amparo Avaria,
Inés Gómez,
María Margaix, Mariam Ibañez,
Irene Luna,
Lourdes Cordón,
Mónica Roig,
Miguel A Sanz,
Meletios A Dimopoulos,
Javier de la Rubia
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ABSTRACT: Osteonecrosis of the jaw is an uncommon but potentially serious complication of bisphosphonate therapy in multiple myeloma. Previous studies showed that the presence of one or two minor alleles of the cytochrome P450, subfamily 2C polypeptide 8 gene (CYP2C8) polymorphism rs1934951 was an independent prognostic marker associated with development of osteonecrosis of the jaw in multiple myeloma patients treated with bisphosphonates. The aim of this study was to validate the frequency of SNP rs193451 in 79 patients with multiple myeloma. In 9 (22%) patients developing osteonecrosis of the jaw, a heterozygous genotype was found, in contrast with those who did not develop osteonecrosis of the jaw (n=4, 11%) or healthy individuals (n=6, 13%). We found no differences in the cumulative risk of developing osteonecrosis of the jaw between patients homozygous and heterozygous for the major allele. We were unable to confirm a significant association between this polymorphism and the risk of developing osteonecrosis of the jaw.
Haematologica 06/2011; 96(10):1557-9. · 6.42 Impact Factor
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ABSTRACT: This study evaluates the incidence and prognostic impact of aberrant methylation of 25 tumor suppressor genes in 40 patients with RARS, a MDS subtype, by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay. Methylation of at least one gene was detected in 18 patients (45%). The genes methylated were CDKN2B (20%), RASSF1 (18%), RARB (10%), CDH13 (7.5%) and FHIT (5%). Patients with at least one methylated gene had a significantly shorter OS than patients without methylated genes. Aberrant methylation is a frequent event in patients with RARS as in patients with high-risk MDS appears to confer a worse prognosis.
Leukemia research 04/2011; 35(4):479-83. · 2.36 Impact Factor
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Esperanza Such,
José Cervera,
Ana Valencia,
Eva Barragán, Mariam Ibañez,
Irene Luna,
Oscar Fuster,
Maria Luz Perez-Sirvent,
Leonor Senent,
Amparo Sempere,
Jesús Martinez,
Guillermo Martín-Aragonés,
Miguel A Sanz
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ABSTRACT: Chromosomal translocations in hematological malignancies often result in novel fusion chimeric genes. We report a case of acute myeloid leukemia with a clonal translocation t(11;12)(p15;q13) displaying morphologic and immunophenotypic features resembling the classical hypergranular subtype of acute promyelocytic leukemia. The gene fused to NUP98 (nucleoporin 98) was detected by comparative genomic hybridization array as the retinoid acid receptor gamma gene (RARG). The involvement of RARG in a chimeric fusion transcript has not been reported previously in human leukemia.
Blood 10/2010; 117(1):242-5. · 9.90 Impact Factor
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ABSTRACT: The usefulness of the new Chromoprobe Multiprobe AML Panel was evaluated in 80 patients with acute myeloid leukemia (AML) in parallel with conventional cytogenetics. We observed a high concordance using both methods, but the panel was very useful in the detection of an inv(16)(p13q22), a cryptic t(15;17)(q22;q21), and a cryptic deletion of the CBFbeta allele not detected with cytogenetics. Moreover, in six of nine patients (67%) without metaphases or with non-evaluable chromosomes, the panel identified three MLL rearrangements, two monosomy 7, one of them also with del(5q), and one inv(16)(p13q22). Our results indicate that the multiprobe panel can be used as a complementary technique for detection of the most important chromosomal abnormalities in AML using small quantities of sample in only one hybridization experiment. It is also capable of reallocating cases without metaphases or with non-evaluable chromosomes in the appropriate cytogenetic risk group.
Leukemia & lymphoma 03/2010; 51(4):680-5. · 2.40 Impact Factor
