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Background and Objectives The prognostic value of myeloid antigen (MyAg) expression in adult acute lymphoblastic leukemia (ALL) is still controversial. The aim of this study was to correlate the expression of MyAg with clinical, hematologic and biological parameters, and to analyze the impact on response to treatment and prognosis in a large series of adult ALL uniformly characterized and treated.Design and Methods We analyzed the expression of the MyAg CD13 and/or CD33 in a cohort of 377 adult patients with de novo ALL enrolled and treated in the GIMEMA ALL 0496 protocol.Results MyAg expression was documented in 35% of the 377 adult ALL cases analyzed. MyAg were significantly more frequently associated with B-lineage ALL (38%) than with T-ALL (24%) (p=0.02). No difference was found with regard to clinical features at presentation; a difference was found only for white cell count (p=0.03), percentage of peripheral blasts (p=0.004) and platelet count (p=0.004). No difference was observed in the expression of MyAg between patients with normal or abnormal cytogenetics or between those with high-risk (BCR-ABL+, ALL1-AF4+, E2A-PBX1+) or low-risk B-lineage ALL. We failed to observe any difference between MyAg-positive and MyAg-negative cases in terms of achievement of complete remission, disease-free survival and overall survival at 5 years.Interpretation and Conclusions Our data indicate that ALL MyAg expression in adults with ALL is not associated with adverse presenting clinical and biological features, and that response to treatment and prognosis is comparable in MyAg-positive and MyAg-negative ALL patients with regards to both complete remission rate and overall survival. We suppose that these result are due to more intensive treatment modalities adopted in the GIMEMA ALL 0496 protocol.

The first description of the human T-lymphotropic virus type 1 (HTLV-1) was made in 1980, followed closely by the discovery of HTLV-2, in 1982. Since then, the main characteristics of these viruses, commonly referred to as HTLV-1/2, have been thoroughly studied. Central and South America and the Caribbean are areas of high prevalence of HTLV-1 and HTVL-2 and have clusters of infected people. The major modes of transmission have been through sexual contact, blood, and mother to child via breast-feeding. HTLV-1 is associated with adult T-cell leukemia/lymphoma (ATL), HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and HTLV-associated uveitis as well as infectious dermatitis of children. More clarification is needed in the possible role of HTLV in rheumatologic, psychiatric, and infectious diseases. Since cures for ATL and HAM/TSP are lacking and no vaccine is available to prevent HTLV-1 and HTLV-2 transmission, these illnesses impose enormous social and financial costs on infected individuals, their families, and health care systems. For this reason, public health interventions aimed at counseling and educating high-risk individuals and populations are of vital importance. In the Americas this is especially important in the areas of high prevalence.

Most cancers and leukemias are preceded by a prolonged period of clinical latency during which cellular, chromosomal and molecular aberrations help move normal cell towards the malignant phenotype. The problem is that premalignant cells are usually indistinguishable from their normal counterparts, thereby ruling out the possibility to investigate the events that govern early leukemogenesis in vivo. Adult T cell leukemia/lymphoma (ATLL) is a T cell malignancy that occurs after a 40-60-year period of clinical latency in about 3-5% of HTLV-1-infected individuals. ATLL cells are monoclonally expanded and harbor an integrated provirus. A persistent oligo/polyclonal expansion of HTLV-1-bearing cells has been shown to precede ATLL, supporting the fact that in ATLL tumor cells arise from a clonally expanding non-malignant cell. It is possible to isolate infected, ie preleukemic, cells during the premalignant asymptomatic phase of the infection, thus providing an exceptional system to study the mechanisms underlying human cancers. Here we review some of the consequences of HTLV-1 on its host cell in vivo, at different stages of infection.

Gene expression profiles were examined in 33 adult patients with T-cell acute lymphocytic leukemia (T-ALL). Nonspecific filtering criteria identified 313 genes differentially expressed in the leukemic cells. Hierarchical clustering of samples identified 2 groups that reflected the degree of T-cell differentiation but was not associated with clinical outcome. Comparison between refractory patients and those who responded to induction chemotherapy identified a single gene, interleukin 8 (IL-8), that was highly expressed in refractory T-ALL cells and a set of 30 genes that was highly expressed in leukemic cells from patients who achieved complete remission. We next identified 19 genes that were differentially expressed in T-ALL cells from patients who either had a relapse or remained in continuous complete remission. A model based on the expression of 3 of these genes was predictive of duration of remission. The 3-gene model was validated on a further set of T-ALL samples from 18 additional patients treated on the same clinical protocol. This study demonstrates that gene expression profiling can identify a limited number of genes that are predictive of response to induction therapy and remission duration in adult patients with T-ALL. (Blood. 2004;103:2771-2778)

Adult T-cell leukaemia/lymphoma (ATLL) is a malignant T-cell proliferation that occurs in 3-5% of individuals infected with human T-cell leukaemia virus-1 (HTLV-1). HTLV-1 infection is also linked to the development of infective dermatitis (ID), an exudative dermatitis of children that has been proposed as a cofactor of ATLL. Here, HTLV-1 replication was investigated over time in a girl with ID and multiparasitic infestation including strongyloidiasis, a disease also known to predispose HTLV-1 carriers to ATLL. Quantitative polymerase chain reaction (PCR) revealed extremely high proviral loads. During the 2-year period of the present study, the proportion of circulating infected cells ranged between 12% and 36%. Quadruplicate linker-mediated PCR amplification of HTLV-1 flanking sequences identified a pattern of extensive and persistent oligoclonal expansion of infected lymphocytes. As viral loads, both the number and the degree of infected T-cell expansion were independent of treatment or clinical signs. However, the temporal fluctuation of proviral loads correlated significantly with the degree of infected T-cell expansion, but not with the overall number of detected clones. This pattern of HTLV-1 replication over time is very different from that observed in asymptomatic carriers and reminiscent of that observed in ATLL, a result consistent with the proposal of ID as an ATLL cofactor.

Background: Chronic lymphoproliferative disorders include a variety of diseases which are often a diagnostic problem for clinical hematologists. Aim: To study prospectively the distribution and incidence of chronic lymphoproliferative disorders in Chile and compare them with those of other Western, Latin American and Oriental countries. Patients and methods: A group of 132 patients were studied in a 36 months period (1999-2001), with a panel of monoclonal antibodies. A score for chronic lymphocytic leukemia was employed to differentiate it from other B-cell disorders. Results: The median age was 63 years old (range 32-94). Most patients had B-cell tumors (109) and the rest (23), T-cell tumors (82% vs 18%). Forty five percent of patients with B-cell tumors had a chronic lymphocytic leukemia (CLL), while the others were disseminated lymphomas. The incidence of T-cell tumors was slightly higher than that of other Western countries. Noteworthy is that the most common of these disorders was adult T cell leukemia/lymphoma (ATLL), in concordance with the high HTLV-1 seroprevalence in Chile. Conclusions: A morphologic, immunophenotypic and pathological study in a large number of patients with chronic lymphoproliferative disorders in Chile, shows a relatively low incidence of CLL when compared to other chronic B-cell tumors and a high representation of ATLL associated to HTLV-1 infection, compared with other Western countries. The lower incidence of CLL in our study might be due to patient's selection and/or underdiagnosis of this disease as a substantial proportion of CLL are asymptomatic (Rev Méd Chile 2003; 131: 291-8).

T-cell lymphoblastic leukemia (T-ALL) cells originate within the thymus from the clonal expansion of T cell precursors. Among thymic stromal elements, epithelial cells (TEC) are known to exert a dominant inductive role in survival and maturation of normal, immature T-cells. In this study we explored the possible effect of TEC on T-ALL cell survival and analyzed the role of interleukin-7 (IL-7) within the microenvironment generated by T-ALL-TEC interactions.T-ALL blasts derived from 10 adult patients were cultured with TEC obtained from human normal thymuses. The level of blast apoptosis was measured by annexin V-propidium iodide co-staining and flow cytometry. The proliferative response of leukemic cells to interaction with TEC was evaluated by thymidine incorporation at various time intervals of culture. To assess the role of IL-7, lympho-epithelial co-cultures were carried out in the presence of anti-IL-7 or anti IL-7R blocking antibodies and the level of apoptosis of T-ALL blasts was analyzed.When T-ALL cells were cultured in the presence of TEC monolayers, the percentage of viable cells increased significantly and this survival was sustained with time in culture. In addition, the interaction with TEC induced a considerable proliferative response in T-ALL cells (15-fold greater than that of the control cells after 7 days of culture). The presence of IL-7 or IL-7R blocking antibodies in lympho-epithelial co-cultures consistently reduced the TEC-mediated apoptosis inhibition in T-ALL blasts (70% decrease).These results point to the role of thymic epithelium in the regulation of T blast survival. In addition, they show that interaction between IL-7 and its receptor has the major role in modulating T-ALL survival within the microenvironment generated by the T-ALL/TEC interaction.

We report a 21-year-old woman who was admitted because of unilateral facial paresis and then developed progressive ascending flaccid tetraparesis with generalized areflexia. Electrodiagnostic studies revealed acute motor axonal polyradiculoneuropathy (AMAN type of Guillain-Barré Syndrome). Further evaluations revealed severe leukocytosis, increased erythrocyte sedimentation rate (ESR), increased protein content and presence of a few lymphocytes in cerebrospinal fluid (CSF), and then presence of human T-cell lymphotropic virus type 1 (HTLV-I) in serum and CSF. Finally, biopsy of the enlarged lymph nodes resulted in the diagnosis of Adult T-cell Leukemia-Lymphoma. The HTLV-1 has been endemic to certain parts of Iran like Khorasan province in the northeast since 1985 with 2.3% prevalence rate of infection. Thus, some rare neurologic complications occasionally occur in this area as a result of being infected with HTLV-1.

The immunophenotype of 304 adult lymphoblastic leukemias (> 18 years) diagnosed on the basis of the FAB criteria was determined at the time of diagnosis using a panel of monoclonal antibodies. The series comprised cases diagnosed and immunophenotyped in 43 Italian centers (GIMEMA Cooperative Group) between April 1988 and June 1991. The immunophenotypic characterization consisted of two consecutive steps. The initial screening was based on the reactivity for TdT, HLA-Dr, CD7, CD10, CD13, CD19, CD24, CD33 and CD41. According to the results obtained, the second level of investigation assessed the positivity for intra cytoplasmic (Cy) Ig, CD1a, CD2, CD3, CD4, CD5, CD8 and CD20. Based on the hierarchical expression of the different B- and T-cell related antigens, each case was assigned to a given differentiation stage. B-lineage ALL were classified in five subgroups (B0-B4) and T-lineage ALL in four subgroups (T0-T3). Cases in which the blasts were lymphoid according to the FAB criteria, but expressed myeloid antigens in association with B- and T-lymphoid markers were defined as hybrid leukemias. As expected, CD10+ cases (B2-B3) were the most frequent within the B-lineage ALL (83.2% of cases). CyIg+ (B3) accounted for about 20% of CD10+ ALL. Twenty eight cases (13.4%) were at a pre-cALL stage (B0-B1) and of these, 8 (3.8% of the total series) were positive only for TdT and HLA-Dr (B0). Intermediate and mature thymic phenotypes (T2-T3) were predominant within the T-ALL (67.2%) groups. Five cases, were positive only for TdT and CD7 (CD5+), and classified as T0. 9.2% of cases fulfilled the definition of hybrid leukemia, largely in view of the co-expression of B-lymphoid and myeloid markers.(ABSTRACT TRUNCATED AT 250 WORDS)

We have investigated the functional relevance of c-myb expression for DNA synthesis in patients' T-leukemia cells. [3H]Thymidine incorporation assays of 32 patients' leukemia cells exposed in vitro to c-myb sense or antisense oligodeoxynucleotides served to define two groups of patients: a responder group whose leukemia cells showed 2- to 16-fold lower levels of [3H]thymidine incorporation in c-myb antisense-treated cultures than in c-myb sense-treated cultures (20 patients) and a nonresponder group whose cells showed comparable [3H]thymidine incorporation levels in either c-myb sense- or antisense-treated cultures (12 patients). Down-regulation of c-myb mRNA levels in cells exposed to c-myb antisense oligodeoxynucleotides was comparable in both groups of patients, indicating that differential sensitivity to c-myb antisense oligodeoxynucleotides was not due to differential uptake of these oligodeoxynucleotides. DNA polymerase alpha mRNA levels were down-regulated in cells from the responders but were unaffected in the nonresponder group. These results suggest that c-myb is required for DNA synthesis in cells of many but not all T-leukemia patients and that leukemia cells in which DNA synthesis is not inhibited despite down-regulation of c-myb expression may have undergone some genetic change(s) that obviate(s) the requirement for myb protein.