1,453 research outputs found
Hybrid phenotypes and lineage promiscuity in acute leukemia
Clinical data indicate that AL are heterogeneous diseases with variable responsiveness to chemotherapeutic agents. Based on this evidence, the efforts of most investigators are aimed at providing rapid identification of AL features predictive of distinct prognostic outcomes. A considerable number of reagents (including MoAb and molecular probes) available from commercial sources has been widely used for diagnostic purpose, leading to the identification of "inappropriate" antigen expression and to diagnoses of "mixed" AL (M-AL). The latter still lacks adequate definition and identification criteria, but is frequently reported as a novel entity associated with poor clinical outcome. The use of more accurate methodologic approaches, as well as a better elucidation of normal hemopoietic cell characteristics suggest that true M-AL occur quite rarely: the features of normal precursor counterparts are more frequently conserved. "Ectopic" marker expression, however, which should not be interpreted as reflecting lineage infidelity, may in some instances explain different clinical courses in AL patients. Further elucidation of normal stem cell features, and adequate standardization of AL immunophenotyping--to be performed under proper technical conditions--are needed for a better evaluation of M-AL, both in terms of diagnosis and classification, as well as regarding their clinical significance
Additive effects in the induction of apoptosis in leukemic cells by WT1 and BCR-ABL specific siRNA
Acute myeloid leukemia developing in patients with autoimmune diseases.
Acknowledgments: the authors gratefully acknowledge the generous support of Dr. Isabel Cunningham, for her intellectual input and editorial assistance. The authors would also like to thank Dr. Gabriele Mazzitelli, Tor-Vergata Digital Library, for his prompt response in providing the original full text of the reviewed literature. Prof. F. Lo-Coco acknowledges the support from the AIL and AIRC
Body cavity lymphoma.
Body cavity lymphomas (BCLs) are a heterogeneous group of rare, primary non-Hodgkin's lymphomas that proliferate within the serous body cavities and result in recurrent effusions. This review is mainly focussed on the distinct entity primary effusion lymphoma (PEL) wherein the tumor clone is infected by human herpesvirus-8, the etiologic agent of Kaposi's sarcoma. In addition, we briefly discuss here recent data regarding other BCL types. The latter include a subset with no evidence of herpesvirus 8 which is associated with Epstein-Barr virus (pyothorax-associated lymphoma, PAL), the BCL forms associated to hepatitis C virus-related cirrhosis or alcohol-related cirrhosis and, finally, non-neoplastic forms mimicking lymphomatous effusions
Using patient-reported health status to improve prognostic assessment in patients with acute myeloid leukemia: Current challenges and future applications
Diagnostic and prognostic advances in the immunophenotypic and genetic characterization of acute leukaemia
Acute promyelocytic leukemia: A model for the role of molecular diagnosis and residual disease monitoring in directing treatment approach in acute myeloid leukemia
Acute promyelocytic leukemia (APL) is characterized by a number of features that underpin the need for rapid and accurate diagnosis and demand a highly specific treatment approach. These include the potentially devastating coagulopathy, sensitivity to anthracycline-based chemotherapy regimens, as well as unique responses to all-trans retinoic acid and arsenic trioxide that have revolutionized therapy over the last decade. The chromosomal translocation t(15;17) which generates the PML-RARalpha fusion gene has long been considered the diagnostic hallmark of APL; however, this abnormality is not detected in approximately 10% cases with successful karyotype analysis. In the majority of these cases, the PML-RARalpha fusion gene is still formed, resulting from insertion events or more complex rearrangements. These cases share the beneficial response to retinoids and favorable prognosis of those with documented t(15;17), underscoring the clinical relevance of molecular analyses in diagnostic refinement. In other cases of t(15;17) negative APL, various chromosomal rearrangements involving 17q21 have been documented leading to fusion of RARalpha to alternative partners, namely PLZF, NPM, NuMA and STAT5b. The nature of the fusion partner has a significant bearing upon disease characteristics, including sensitivity to retinoids and arsenic trioxide. APL has provided an exciting treatment model for other forms of AML whereby therapeutic approach is directed towards cytogenetically and molecularly defined subgroups and further modified according to response as determined by minimal residual disease (MRD) monitoring. Recent studies suggest that rigorous MRD monitoring, coupled with pre-emptive therapy at the point of molecular relapse improves survival in the relatively small subgroup of PML-RARalpha positive patients with 'poor risk' disease. Advent of 'real-time' quantitative RT-PCR technology seems set to yield further improvements in the predictive value of MRD assessment, achieve more rapid sample throughput and facilitate inter- and intra-laboratory standardization, thereby enabling more reliable comparison of data between international trial groups
Novel strategies in treatment of acute promyelocytic leukemia
Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia characterized by t(15;17) and a life-threatening coagulopathy. Once highly fatal, nowadays standard treatment approaches with all-trans retinoic acid (ATRA) along with chemotherapy allows curing up to 80-85% of cases. In the past decade, arsenic trioxide used alone or in combination with ATRA has demonstrated high efficacy in APL, and is currently regarded as the gold standard for treatment of relapsed cases. Chemotherapy-free approaches based on the combination of arsenic trioxide and ATRA are currently being tested against standard ATRA and chemotherapy in randomized clinical trials for frontline therapy of APL
Therapy of acute myeloid leukemia: towards a patient-oriented, risk-adapted approach
The successful use of differentiating treatment for patients with acute promyelocytic leukemia (APL) suggests that other acute myeloid leukemias (AML) may benefit from tailored and subtype-specific therapy. Despite the fact that new drugs specifically targeting AML genetic lesions have not yet been developed, distinct karyotypic categories have been identified which may deserve differentiated treatment. In addition, molecular assays to assess response to therapy more sensitively are now available for several AML subsets. In this review, we discuss the role of genetic characterization in the therapy of AML, and the investigative efforts which we believe are still needed for the design of tailored treatment for each and every patient with this disease
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