Baratella M.,University of Insubria |
Forlani G.,University of Insubria |
Raval G.U.,University of Insubria |
Raval G.U.,Hematopathology Laboratory |
And 5 more authors.
PLoS Neglected Tropical Diseases | Year: 2017
HTLV-1 is the causative agent of a severe form of adult T cell leukemia/Lymphoma (ATL), and of a chronic progressive neuromyelopathy designated HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Two important HTLV-1-encoded proteins, Tax-1 and HBZ, play crucial roles in the generation and maintenance of the oncogenic process. Less information is instead available on the molecular and cellular mechanisms leading to HAM/TSP. More importantly, no single specific biomarker has been described that unambiguously define the status of HAM/TSP. Here we report for the first time the finding that HBZ, described until now as an exclusive nuclear protein both in chronically infected and in ATL cells, is instead exclusively localized in the cytoplasm of peripheral blood mononuclear cells (PBMC) from patients suffering of HAM/TSP. Interestingly, at the single cell level, HBZ and Tax-1 proteins are never found co-expressed in the same cell, suggesting the existence of mechanisms of expression uncoupling of these two important HTLV-1 viral products in HAM/TSP patients. Cells expressing cytoplasmic HBZ were almost exclusively found in the CD4+ T cell compartment that was not, at least in a representative HAM/TSP patient, expressing the CD25 marker. Less than 1 percent CD8+ T cells were fond positive for HBZ, while B cells and NK cells were found negative for HBZ in HAM/TSP patients. Our results identify the cytoplasmic localization of HBZ in HAM/TSP patient as a possible biomarker of this rather neglected tropical disease, and raise important hypotheses on the role of HBZ in the pathogenesis of the neuromyelopathy associated to HTLV-1 infection. © 2017 Baratella et al.
Dawson A.J.,Cytogenetics Laboratory |
Dawson A.J.,University of Manitoba |
Yanofsky R.,University of Manitoba |
Vallente R.,Genomic Center for Cancer Research and Diagnostics |
And 5 more authors.
Current Oncology | Year: 2011
Most patients with acute lymphocytic leukemia (ALL) are reported to have acquired chromosomal abnormalities in their leukemic bone marrow cells. Many established chromosome rearrangements have been described, and their associations with specific clinical, biologic, and prognostic features are well defined. However, approximately 30% of pediatric and 50% of adult patients with ALL do not have cytogenetic abnormalities of clinical significance. Despite significant improvements in outcome for pediatric ALL, therapy fails in approximately 25% of patients, and these failures often occur unpredictably in patients with a favorable prognosis and "good" cytogenetics at diagnosis. It is well known that karyotype analysis in hematologic malignancies, although genome-wide, is limited because of altered cell kinetics (mitotic rate), a propensity of leukemic blasts to undergo apoptosis in culture, overgrowth by normal cells, and chromosomes of poor quality in the abnormal clone. Array comparative genomic hybridization (aCGH- "microarray") has a greatly increased genomic resolution over classical cytogenetics. Cytogenetic microarray, which uses genomic dna, is a powerful tool in the analysis of unbalanced chromosome rearrangements, such as copy number gains and losses, and it is the method of choice when the mitotic index is low and the quality of metaphases is suboptimal. The copy number profile obtained by microarray is often called a "molecular karyotype." In the present study, microarray was applied to 9 retrospective cases of pediatric ALL either with initial high-risk features or with at least 1 relapse. The conventional karyotype was compared to the "molecular karyotype" to assess abnormalities as interpreted by classical cytogenetics. Not only were previously undetected chromosome losses and gains identified by microarray, but several karyotypes interpreted by classical cytogenetics were shown to be discordant with the microarray results. The complementary use of microarray and conventional cytogenetics would allow for more sensitive, comprehensive, and accurate analysis of the underlying genetic profile, with concomitant improvement in prognosis and treatment, not only for pediatric ALL, but for neoplastic disorders in general. © 2011 Multimed Inc.
Wood B.L.,University of Washington |
Wood B.L.,Hematopathology Laboratory
Journal of Hematopathology | Year: 2015
Acute leukemia is the most common group of neoplasms diagnosed in the pediatric population, the most frequent being acute lymphoblastic leukemia of B cell lineage. Immunophenotyping has come to play an integral role in the enumeration of leukemic populations, assignment of lineage, identification of prognostic subgroups, and subsequent post-therapeutic monitoring. This review will describe the current status of flow cytometric immunophenotyping as applied to the diagnosis and monitoring of pediatric patients with acute leukemia and suggest areas for future investigation. © 2014, Springer-Verlag Berlin Heidelberg.
Rahman K.,Rajiv Gandhi Cancer Institute and Research Center |
Subramanian P.G.,Hematopathology Laboratory |
Kadam P.A.,Cancer Cytogenetics Laboratory |
Gadage V.,Hematopathology Laboratory |
And 10 more authors.
Indian Journal of Pathology and Microbiology | Year: 2012
Background: Leukemic involvement in mantle cell lymphoma (MCL) is common, and can be secondary to nodal or extranodal disease or can be de-novo. There is paucity of literature that describes the morphological spectrum. Aim: This study was aimed at studying the morphological spectrum of leukemic MCL and to correlate the morphology with other features. Materials and Methods: Twenty six such cases diagnosed over a period of four years were studied. Peripheral blood and bone marrow aspiration smears stained with Wrights stain were examined by three hematopathologists. Immunophenotyping was done using multicolor flow cytometry. Fluorescence in situ hybridization (FISH) done in 12 cases showed t(11;14)(q13:q32). Results: Six cases had de-novo leukemic involvement; while 20 cases had secondary involvement. Morphologically, the cells were small (less than twice the size of red blood cell) or large. Small cell morphology in turn showed irregular nuclear border (n=13) or round nuclear contour (n=6). Large cells had blastic morphology (n=5) or had central prominent nucleoli resembling prolymhphocytes (n=2). Twenty cases showed characteristic immunophenotype of CD5+/CD19+/CD20+/FMC7+/CD10-/CD23-and light chain restrictions. Three cases expressed CD23 and two cases were negative for FMC7. Five out of 12 cases, where FISH was done, showed cytogenetic abnormalities in addition to t(11;14)(q13;q32). Conclusion: Morphological spectrum of leukemic MCL ranges from small cells resembling chronic lymphocytic leukemia (CLL) or follicular lymphoma (FL) to large cell mimicking prolymphocytic leukemia (PLL) or acute leukemia. Large cell morphology was associated with more frequent additional cytogenetic abnormality as well as a poorer outcome.