34 research outputs found
p53 Aberrations do not predict individual response to fludarabine in patients with B-cell chronic lymphocytic leukaemia in advanced stages Rai III/IV
Abnormalities of p53 have been associated with short survival and non-response to therapy in chronic lymphocytic leukaemia (CLL). We have evaluated the rate of response to fludarabine as first-line therapy in 54 patients with advanced stage CLL, analysing the cytogenetic profile, aberrations in p53, including the methylation status of its promoter, and the immunoglobulin heavy-chain variable-region (IGVH) mutation status. According to the advanced stage of the disease in this series, 75% of patients presented genetic aberrations associated with poor prognosis: del(17p) and/or del(11q), and no-mutated IGVH genes. Ten patients (18.5%) had methylation in the promoter region of p53. Eighty-three per cent of patients treated achieved a response, with a high rate of complete remission (47.6%). Although we found a significant correlation between failures and the presence of p53 aberrations (P = 0.0065), either with methylation (P = 0.018) or deletion (P = 0.015), 64% of the patients with aberrations in this gene responded to treatment (11/17), suggesting that fludarabine induces high remission rates, even in these patients. This is the first time that the significance of p53 promoter methylation status is described in this pathology, and our data support that this epigenetic phenomenon could be involved in the pathogenesis and clinical evolution of CLL
t(10;16)(q22;p13) and MORF-CREBBP fusion is a recurrent event in acute myeloid leukemia
Recently, it was shown that t(10;16)(q22;p13) fuses the MORF and CREBBP genes in a case of childhood acute myeloid leukemia (AML) M5a, with a complex karyotype containing other rearrangements. Here, we report a new case with the MORF-CREBBP fusion in an 84-year-old patient diagnosed with AML M5b, in which the t(10;16)(q22;p13) was the only cytogenetic aberration. This supports that this is a recurrent pathogenic translocation in AML
Edelfosine lipid nanosystems overcome drug resistance in leukemic cell lines
Although current therapies have improved leukemia survival rates, adverse drug effects and relapse are frequent. Encapsulation of edelfosine (ET) in lipid nanoparticles (LN) improves its oral bioavailability and decreases its toxicity. Here we evaluated the efficacy of ET-LN in myeloid leukemia cell lines. Drug-loaded LN were as effective as free ET in sensitive leukemia cell lines. Moreover, the encapsulated drug overcame the resistance of the K562 cell line to the drug. LN containing ET might be used as a promising drug delivery system in leukemia due to their capacity to overcome the in vivo pitfalls of the free drug and their efficacy in vitro in leukemia cell lines
Lack of Bcr-Abl point mutations in chronic myeloid leukemia patients in chronic phase before imatinib treatment is not predictive of response
Desarrollo de la técnica de FICTION como nueva herramienta para el diagnóstico precoz de cáncer de pulmón
El cáncer de pulmĂłn es una de las causas de muerte más frecuentes en el mundo occidental. La supervivencia global de los pacientes no supera el 15% a los 5 años, debido principalmente a que la mayor parte de los casos se diagnostican en estadios avanzados. Además de la prevenciĂłn primaria, mediante la reducciĂłn del consumo de tabaco, son necesarias nuevas tecnologĂas para el diagnĂłstico precoz de la enfermedad.
Estudios recientes han demostrado que el TAC helicoidal del tórax es efectivo en la detección de nódulos pulmonares malignos en estadios precoces. En la actualidad se está valorando su eficacia en series amplias de pacientes de alto riesgo.
Recientemente se ha desarrollado una nueva tĂ©cnica de citogenĂ©tica molecular, el FICTION (Fluorescence Immunophenotyping and Interphase Cytogenetics as a Tool for the Investigation of Neoplasms). Esta tĂ©cnica permite el análisis simultáneo de marcadores inmunofenotĂpicos y alteraciones genĂ©ticas presentes en las cĂ©lulas tumorales. El objetivo de nuestro proyecto es su puesta a punto para el estudio de muestras de esputo y lavado broncoalveolar de pacientes con cáncer de pulmĂłn. El fin Ăşltimo es estudiar la posibilidad de que esta tĂ©cnica pueda ser utilizada, junto con el TAC helicoidal, en programas de detecciĂłn precoz de cáncer de pulmĂłn, para pacientes de alto riesgo.
En este trabajo presentamos una revisiĂłn de la contribuciĂłn de las distintas tĂ©cnicas de citogenĂ©tica al estudio del cáncer de pulmĂłn y la metodologĂa de trabajo que vamos a llevar a cabo en nuestro proyecto
Cryptic ins(2;11) with clonal evolution showing amplification of 11q23-q25 either on hsr(11) or on dmin, in a patient with AML-M2
Remission of acute monocytic leukemia, secondary to treatment with epipodophyllotoxins, in a patient with t(8;16)(p11;p13) and MYST3-CREBBP fusion
Molecular characterization of a t(1;3)(p36;q21) in a patient with MDS. MEL1 is widely expressed in normal tissues, including bone marrow, and it is not overexpressed in the t(1;3) cells
Patients with myeloid malignancies and either the 3q21q26 syndrome or t(1;3)(p36;q21) have been reported to share similar clinicopathological features and a common molecular mechanism for leukemogenesis. Overexpression of MDS1/EVI1 (3q26) or MEL1/PRDM16 (1p36), both members of the PR-domain family, has been directly implicated in the malignant transformation of this subset of neoplasias. The breakpoints in both entities are outside the genes, and the 3q21 region, where RPN1 is located, seems to act as an enhancer. MEL1 has been reported to be expressed in leukemia cells with t(1;3) and in the normal uterus and fetal kidney, but neither in bone marrow (BM) nor in other tissues, suggesting that this gene is specific to t(1;3)-positive MDS/AML. We report the molecular characterization of a t(1;3)(p36;q21) in a patient with MDS (RAEB-2). In contrast to previous studies, we demonstrate that MEL1, the PR-containing form, and MEL1S, the PR-lacking form, are widely expressed in normal tissues, including BM. The clinicopathological features and the breakpoint on 1p36 are different from cases previously described, and MEL1 is not overexpressed, suggesting a heterogeneity in myeloid neoplasias with t(1;3)
Insertion (22;9)(q11;q34q21) in a patient with chronic myeloid leukemia characterized by fluorescence in situ hybridization
An unusual cytogenetic rearrangement, described as ins(22;9)(q11;q34q21), was detected in a 49-year-old male patient diagnosed with chronic myeloid leukemia (CML). Reverse transcriptase polymerase chain reaction (RT-PCR) revealed a b3a2 fusion transcript. In order to confirm the cytogenetic findings and fully characterize the inverted insertion, we performed fluorescence in situ hybridization (FISH) assays using locus-specific and whole chromosome painting probes. Our FISH analysis showed the presence of the BCR/ABL fusion gene, verified the insertion and determined that the breakpoint on chromosome 22 where the insertion took place was located proximal to the BCR gene and distal to the TUPLE1 gene on 22q11
NUP98 is fused to HOXA9 in a variant complex t(7;11;13;17) in a patient with AML-M2
The t(7;11)(p15;p15.4) has been reported to fuse the NUP98 gene (11p15), a component of the nuclear pore complex, with the class-1 homeobox gene HOXA9 at 7p15. This translocation has been associated with myeloid leukemias, predominantly acute myeloid leukemia (AML) M2 subtype with trilineage myelodysplastic features, and with a poor prognosis. The derived fusion protein retains the FG repeat motif of NUP98 N-terminus and the homeodomain shared by the HOX genes, acting as an oncogenic transcription factor critical for leukemogenesis. We report here a new complex t(7;11)-variant, i.e., t(7;11;13;17)(p15;p15;p?;p1?2) in a patient with AML-M2 and poor prognosis. The NUP98-HOXA9 fusion transcript was detected by RT-PCR, suggesting its role in the malignant transformation as it has been postulated for other t(7;11)-associated leukemias. No other fusion transcripts involving the NUP98 or HOXA9 genes were present, although other mechanisms involving several genes on chromosomes 13 and 17 may also be involved. To our knowledge, this is the first t(7;11) variant involving NUP98 described in hematological malignancies