Publications (103) View all
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Article: Acquisition of t(11;14) in a patient with chronic lymphocytic leukemia carrying both t(14;19)(q32;q13.1) and +12.
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ABSTRACT: A rare recurrent chromosomal translocation, t(14;19)(q32;q13), has been identified in a variety of B cell malignancies, including chronic lymphocytic leukemia (CLL). We report a unique case of CLL in a patient carrying both trisomy 12 and t(14;19) (q32;q13.1), in whom t(11;14)(q13;q32) developed at relapse. The patient was a 77-year-old woman, and her lymphoma cells at presentation showed CD5(+) , CD10(-) , CD19(+) , CD20(+) (dim), CD23(+) , CD38(+) , CD11c(+) . At relapse, the patient's lymphoma cells showed positive staining for cyclin D1 in addition to CD5, CD20, and CD23. Lymphoma cells in specimens at both presentation and relapse were positive for lymphoid enhancer factor 1 (LEF1) and negative for sex-determining region Y-box 11 (SOX11). IGH-BCL1 FISH became positive at relapse. Split FISH assay using BCL1, BCL3, IGH, and CCND1 probes on lymph node specimens obtained at presentation and at autopsy confirmed that the translocation of BCL3 was solely detected in the lymph node at presentation and fusion probe detected BCL3 and CCND1 translocations in the specimen at autopsy. These observations indicated that IGH-BCL3 and IGH-CCND1 had occurred in the same clone after treatment of the disease. In line with immunohistochemical and cytogenetic studies, additional PCR analysis of the FR3-JH region showed the same sequence derived from IGHV4-34 in specimens obtained at disease onset and relapse. This article is protected by copyright. All rights reserved.European Journal Of Haematology 04/2013; · 2.61 Impact Factor -
Article: Prognostic Value of High Thymidine Kinase Activity in Previously Untreated Diffuse Large B-Cell Lymphoma Patients Treated by R-CHOP.
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ABSTRACT: ABSTRACT The purpose of this study was to investigate prognostic factors for overall survival (OS) among previously untreated diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP. We evaluated four biological parameters including thymidine kinase activity (TK). This study looked at 183 patients. The median level of TK was 14.0 IU/L, which we chose as the cut-off. After a median follow-up time of 53.0 months, OS rate at 4 years in the high TK arm and low TK arm were 46.7% and 66.7% (p = .001). By multivariate analysis, OS was significantly worse in high-TK arm (hazard ratio 2.705; p = .045). Complete response (CR) rate among high TK arm was significantly worse than low TK arm. OS was significantly better in patients who had achieved CR than partial response or less. In conclusion, high TK activity was a strong predictor for short OS and poor response among patients with previously untreated DLBCL treated with R-CHOP.Leukemia & lymphoma 03/2013; · 2.40 Impact Factor -
Article: Transforming mutations of RAC guanosine triphosphatases in human cancers.
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ABSTRACT: Members of the RAS superfamily of small guanosine triphosphatases (GTPases) transition between GDP-bound, inactive and GTP-bound, active states and thereby function as binary switches in the regulation of various cellular activities. Whereas HRAS, NRAS, and KRAS frequently acquire transforming missense mutations in human cancer, little is known of the oncogenic roles of other small GTPases, including Ras-related C3 botulinum toxin substrate (RAC) proteins. We show that the human sarcoma cell line HT1080 harbors both NRAS(Q61K) and RAC1(N92I) mutant proteins. Whereas both of these mutants were able to transform fibroblasts, knockdown experiments indicated that RAC1(N92I) may be the essential growth driver for this cell line. Screening for RAC1, RAC2, or RAC3 mutations in cell lines and public databases identified several missense mutations for RAC1 and RAC2, with some of the mutant proteins, including RAC1(P29S), RAC1(C157Y), RAC2(P29L), and RAC2(P29Q), being found to be activated and transforming. P29S, N92I, and C157Y mutants of RAC1 were shown to exist preferentially in the GTP-bound state as a result of a rapid transition from the GDP-bound state, rather than as a result of a reduced intrinsic GTPase activity. Activating mutations of RAC GTPases were thus found in a wide variety of human cancers at a low frequency; however, given their marked transforming ability, the mutant proteins are potential targets for the development of new therapeutic agents.Proceedings of the National Academy of Sciences 02/2013; · 9.68 Impact Factor -
Article: Prognostic significance of programmed cell death-1-positive cells in follicular lymphoma patients may alter in the rituximab era.
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ABSTRACT: Programmed cell death-1 (PD-1) is involved in one of the inhibitory pathways of the B7-cluster of differentiation (CD)28 family; this pathway is known to be involved in the attenuation of T cell responses and promotion of T cell tolerance. PD-1 is known to negatively regulate T cell receptor-mediated proliferation and cytokine production, lead to alternation in the tumor microenvironment. Although several studies have shown that high levels of PD-1-positive cells in follicular lymphoma (FL) patients influence their prognosis, those studies included patients treated without rituximab, and the prognostic impact of PD-1 positivity in the rituximab-era (R-era) has not yet been elucidated. We retrospectively studied 82 patients with FL uniformly treated with standard R-CHOP therapy at 6 institutions between 2001 and 2009 (median follow-up for survivors: 55 months). We also collected and examined biopsy specimens for diagnosis with respect to PD-1 positivity. The PD-1 positivity was significantly higher in male patients and patients with high beta-2 microglobulin (B2M ≥ 3.0) (p = 0.03 and 0.003, respectively). Three-year progression free survival (PFS) and overall survival (OS) were 60% and 86%, respectively. By univariate analysis, elevated LDH (p = 0.07) worsened PFS. Male gender (p = 0.03), high FLIPI score (p = 0.05), and high B2M levels (p = 0.08) worsened OS. Multivariate analysis detected no significant prognostic factors, including PD-1 positivity. However, in male subgroup, high levels of PD-1-positive cells were found to be a prognostic factor for PFS. Addition of rituximab might have altered the prognostic impact of PD-1 positive cells. © 2013 John Wiley & Sons A/S.European Journal Of Haematology 01/2013; · 2.61 Impact Factor -
Article: A low-grade B-cell lymphoma with prolymphocytic/paraimmunoblastic proliferation and IRF4 rearrangement.
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ABSTRACT: NA.Haematologica 01/2013; · 6.42 Impact Factor
