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Vellore, India

Martin-Perez D.,Lymphoma Group | Sanchez E.,Hospital Nuestra Senora del Prado | Maestre L.,Monoclonal Antibodies Unit | Suela J.,Cytogenetics Unit | And 6 more authors.
American Journal of Pathology | Year: 2010

Polycomb proteins are known to be of great importance in human cancer pathogenesis. SUZ12 is a component of the Polycomb PRC2 complex that, along with EZH2, is involved in embryonic stem cell differentiation. EZH2 plays an essential role in many cancer types, but an equivalent involvement of SUZ12 has not been as thoroughly demonstrated. Here we show that SUZ12 is anomalously expressed in human primary tumors, especially in mantle cell lymphoma (MCL), pulmonary carcinomas and melanoma, and is associated with gene locus amplification in some cases. Using MCL as a model, functional and genomic studies demonstrate that SUZ12 loss compromises cell viability, increases apoptosis, and targets genes involved in central oncogenic pathways associated with MCL pathogenesis. Our results support the hypothesis that the abnormal expression of SUZ12 accounts for some of the unexplained features of MCL, such as abnormal DNA repair and increased resistance to apoptosis. Copyright © American Society for Investigative Pathology. Source


Philip C.,Christian Medical College | George B.,Christian Medical College | Ganapule A.,Christian Medical College | Korula A.,Christian Medical College | And 11 more authors.
British Journal of Haematology | Year: 2015

The management of acute myeloid leukaemia (AML) in India remains a challenge. In a two-year prospective study at our centre there were 380 newly diagnosed AML (excluding acute promyelocytic leukaemia, AML-M3) patients. The median age of newly diagnosed patients was 40 years (range: 1-79; 12·3% were ≤ 15 years, 16·3% were ≥ 60 years old) and there were 244 (64·2%) males. The median duration of symptoms prior to first presentation at our hospital was 4 weeks (range: 1-52). The median distance from home to hospital was 580 km (range: 6-3200 km). 109 (29%) opted for standard of care and were admitted for induction chemotherapy. Of the 271 that did not take treatment the major reason was lack of financial resources in 219 (81%). There were 27 (24·7%) inductions deaths and of these, 12 (44·5%) were due to multidrug-resistant gram-negative bacilli and 12 (44·5%) showed evidence of a fungal infection. The overall survival at 1 year was 70·4% ± 10·7%, 55·6% ± 6·8% and 42·4% ± 15·6% in patients aged ≤15 years, 15 - 60 years and ≥60 years, respectively. In conclusion, the biggest constraint is the cost of treatment and the absence of a health security net to treat all patients with this diagnosis. © 2015 The Authors. Source


Chendamarai E.,Christian Medical College | Balasubramanian P.,Christian Medical College | George B.,Christian Medical College | Viswabandya A.,Christian Medical College | And 12 more authors.
Blood | Year: 2012

Data on minimal residual disease (MRD) monitoring in acute promyelocytic leukemia (APL) are available only in the context of conventional all-trans retinoic acid plus chemotherapy regimens. It is recognized that the kinetics of leukemia clearance is different with the use of arsenic trioxide (ATO) in the treatment of APL. We undertook a prospective peripheral blood RT-PCR-based MRD monitoring study on patients with APL treated with a single agentATO regimen.Atotal of 151 patients were enrolled in this study. A positive RT-PCR reading at the end of induction therapy was significantly associated on a multivariate analysis with an increased risk of relapse (relative risk = 4.9; P = .034). None of the good risk patients who were RT-PCR negative at the end of induction relapsed. The majority of the relapses (91%) happened within 3 years of completion of treatment. After achievement of molecular remission, the current MRD monitoring strategy was able to predict relapse in 60% of cases with an overall sensitivity and specificity of 60% and 93.2%, respectively. High-risk group patients and those that remain RT-PCR positive at the end of induction are likely to benefit from serial MRD monitoring by RT-PCR for a period of 3 years from completion of therapy. © 2012 by The American Society of Hematology. Source


Van Rijk A.,Radboud University Nijmegen | Svenstroup-Poulsen T.,Copenhagen University | Jones M.,University of Oxford | Cabecadas J.,Instituto Portugues Of Oncologia | And 7 more authors.
Haematologica | Year: 2010

Background: Malignant lymphomas are classified based on morphology, immunophenotype, genetics and clinical features. The pathological diagnosis is generally considered difficult and prone to mistakes. Since non-random chromosomal translocations are specifically involved in specific entities, their detection is an important adjunct for increasing the reliability of the diagnosis. Recently, split-signal fluorescence in situ hybridization has become available as a robust method to detect chromosomal breaks in paraffin-embedded formalin-fixed tissues. A bright field approach would bring this technology within the reach of every pathology laboratory. Design and Methods: Our study was initiated to determine the consistency between chromogenic in situ hybridization and fluorescence in situ hybridization, both using split-signal probes developed for the detection of chromosomal breaks. Five hundred and forty cases of 11 lymphoma entities and reactive, benign lymphoid tissues, collected from eight different pathology laboratories, placed on 15 fluorescence in situ hybridization pre-stained tissue microarray slides, were double stained for the chromogenic hybridization. For each core morphology and actual signal were compared to the original fluorescence hybridization results. In addition, hematoxylin background staining intensity and signal intensity of the double-staining chromogenic in situ hybridization procedure were analyzed. Results: With respect to the presence or absence of chromosomal breaks, 97% concordance was found between the results of the two techniques. Hematoxylin background staining intensity and signal intensity were found to correspond. The overall morphology after doublestaining chromogenic in situ hybridization had decreased compared to the initial morphology scored after split-signal fluorescence in situ hybridization staining. Conclusions: We conclude that double-staining chromogenic in situ hybridization is equally reliable as fluorescence in situ hybridization in detecting chromosomal breaks in lymphoid tissue. Although differences in morphology, hematoxylin staining and chromogenic signal intensity vary between the tumor entities none of the entities appeared more easy or difficult to score. ©2010 Ferrata Storti Foundation. Source


Parihar M.,Cytogenetics Unit | Koshy B.,Christian Medical College | Srivastava V.M.,Cytogenetics Unit
Indian Journal of Human Genetics | Year: 2013

Chromosomal abnormalities are seen in nearly 1% of live born infants. We report a 5-year-old boy with the clinical features of Down syndrome, which is the most common human aneuploidy. Cytogenetic analysis showed a mosaicism for a double aneuploidy, Down syndrome and XYY. The karyotype was 47, XY,+21[19]/48, XYY,+21[6]. ish XYY (DXZ1 × 1, DYZ1 × 2). Mosaic double aneuploidies are very rare and features of only one of the aneuploidies may predominate in childhood. Cytogenetic analysis is recommended even if the typical features of a recognized aneuploidy are present so that any associated abnormality may be detected. This will enable early intervention to provide the adequate supportive care and management. Source

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