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La leucemia linfoblástica aguda representa más del 30% de todos los tipos de cáncer en niños entre 0 y 9 años a nivel global. En el Perú, no se ha evaluado si la lactancia materna exclusiva es un factor protector para la leucemia linfoblástica. Objetivo: Identificar los factores protectores y de riesgo asociados a la leucemia linfoblástica aguda en niños y adolescentes entre 0 y 13 años en un hospital nacional, Lima, Perú. Pacientes y Método: Estudio observacional, analítico, diseño caso-control. Se evaluaron 112 casos con diagnóstico de leucemia linfoblástica y 229 controles. Los datos fueron recogidos por entrevistas a las madres de ambos grupos. Se estimó la magnitud de la asociación entre la leucemia y la lactancia exclusiva mediante el odds ratio (OR) y regresión logística multivariado en Stata v 12. Resultados: El 50,9% (57/112) de los casos y el 51,5% (118/229) de los controles fueron del género masculino. La media de edad entre los casos fue 6,7 ± 3,2 años y entre los controles 5,7 ± 3,5 años. La media de edad de la madre entre los casos fue 35,9 ± 6,5 y entre los controles fue 34,1 ± 7,1 años. La lactancia materna exclusiva se asocia a menor riesgo de leucemia en un 44% respecto a aquellos que no tuvieron, OR 0,56, p = 0,017, IC 95% (0,35-0,90). La educación secundaria completa se asocia a menor riesgo de leucemia en un 62%, OR 0,38 IC 95% (0,15-0,61). Conclusiones: La lactancia materna exclusiva y la educación secundaria completa de la madre son factores asociados a menor riesgo de leucemia linfoblástica aguda en niños y en adolescentes. Globally, Acute Lymphoblastic Leukemia (ALL), represents more than 30% of all types of cancers in children aged between 0 and 9 years. In Peru, it has not been evaluated whether exclusive breastfeeding (EB) is a protective factor for ALL. Objective: To identify the protective and risk factors associated with acute lymphoblastic leukemia in children aged between 0 and 13 years in a national hospital in Lima, Peru. Patients and Method: Observational, analytical study, case-control design. 112 cases diagnosed with ALL and 229 controls were evaluated. The data were collected by interviews with the mothers of both groups. The magnitude of the association between ALL and EB was estimated using the odds ratio (OR) and multivariate logistic regression in Stata v 12. Results: 50.9% (57/112) of the cases and 51.5% (118/229) of the controls were male. The mean age of the cases was 6.7 ± 3.2 years and of the controls 5.7 ± 3.5 years. The mean age of the mothers of the cases was 35.9 ± 6.5 and of the controls was 34.1 ± 7.1 years. EB reduces the risk of ALL by 44% compared with those who did not receive it, OR 0.56, p = 0.017, 95% CI (0.35-0.90). Complete secondary education reduces the risk of ALL by 62%, OR 0.38 CI 95% (0.15-0.61). Conclusions: Exclusive breastfeeding and the mother’s complete secondary education are protective factors for the development of ALL in children and adolescents.

Background Adult T-cell leukemia-lymphoma (ATL) is an aggressive mature lymphoid proliferation associated with poor prognosis. Standard of care includes chemotherapy and/or the combination of zidovudine and interferon-alpha. However, most patients experience relapse less than 6 months after diagnosis. Allogeneic stem cell transplantation is the only curative treatment, but is only feasible in a minority of cases. We previously showed in a mouse model that Arsenic trioxide (As2O3) targets ATL leukemia initiating cells. Results As2O3 consolidation was given in 9 patients with ATL (lymphoma n = 4; acute n = 2; and indolent n = 3), who were in complete (n = 4) and partial (n = 3) remission, in stable (n = 1) and in progressive (n = 1) disease. Patients received up to 8 weeks of As2O3 at the dose of 0.15 mg/kg/day intravenously in combination with zidovudine and interferon-alpha. One patient in progression died rapidly. Of the remaining eight patients, three with indolent ATL subtype showed overall survivals of 48, 53 and 97 months, and duration of response to As2O3 of 22, 25 and 73 months. The other 5 patients with aggressive ATL subtype had median OS of 36 months and a median duration of response of 10 months. Side effects were mostly hematological and cutaneous (one grade 3) and reversible with dose reduction of AZT/IFN and/or As2O3 discontinuation. The virus integration analysis revealed the regression of the predominant malignant clone in one patient with a chronic subtype. Conclusion These results suggest that consolidation with As2O3 could be an option for patients with ATL in response after induction therapy and who are not eligible for allogeneic stem cell transplantation.

Mogamulizumab, a humanized defucosylated anti C-C chemokine receptor 4 monoclonal antibody, has been approved in Japan for the treatment of C-C chemokine receptor 4-positive adult T-cell leukemia/lymphoma. This phase 2 study evaluated efficacy and safety of mogamulizumab in adult T-cell leukemia/lymphoma patients with acute, lymphoma, and chronic subtypes with relapsed/refractory, aggressive disease in the United States, Europe, and Latin America. With stratification by subtype, patients were randomized 2:1 to intravenous mogamulizumab 1.0 mg/kg once weekly for 4 weeks and biweekly thereafter (n = 47) or investigator choice of chemotherapy (n = 24). The primary endpoint, overall response rate confirmed on a subsequent assessment at 8 weeks by blinded independent review, was 11% (95% CI, 4% to 23%) and 0% (95% CI, 0% to 14%) in the mogamulizumab and chemotherapy arms, respectively. Best response was 28% and 8% in the respective arms. The observed hazard ratio for progression-free survival was 0.71 (95% CI, 0.41-1.21) and, after post hoc adjustment for performance status imbalance, 0.57 (95% CI, 0.337-0.983). The most frequent treatment-related adverse events grade ≥3 with mogamulizumab were infusion-related reaction and thrombocytopenia (each 9%). Relapsed/refractory adult T-cell leukemia/lymphoma is an aggressive, poor prognosis disease with a high unmet need. Investigator choice chemotherapy did not result in tumor response in this trial; however, mogamulizumab treatment resulted in 11% confirmed overall response rate, with a tolerable safety profile. This trial was registered at www.clinicaltrials.gov as NCT01626664.

Adult T-cell leukemia/lymphoma belongs to the group of mature T-cell malignancies according to the WHO classification. It constitutes a rare entity and has a strong association with infection by human T-lymphotropic virus 1. In Uruguay, this viral infection is very infrequent and, to our knowledge, no case of adult T-cell leukemia/lymphoma has been previously reported. We describe the case of a woman, immigrant from Peru, who presented with persistent lymphocytosis, intestinal parasitic diseases, and skin involvement. The diagnosis was delayed and the patient died before initiating oncological treatment. We therefore emphasize the relevance of an early clinical suspicion and serology for this virus, especially in patients coming from endemic countries like Peru.

Adult T-cell Leukemia/Lymphoma (ATLL) is classified as a peripheral CD4+ T-cell neoplasm caused by the human T-cell lymphotropic virus type 1 (HTLV-1). Typical symptoms are associated with leukemic infiltration; however, atypical and exaggerated manifestations of verrucous carcinoma have also been described.We present here the case of a patient with multiple skin lesions, ischemic necrosis in the hallux and lymphadenopathies. Biopsies were taken, which showed verrucous epidermal carcinoma and cutaneous lymphoma. Splenomegaly and adenopathy in mesentery, retro peritoneum and lymph node chains in the limbs were observed. Bone marrow examination showed findings compatible with T-cell leukemia/lymphoma; and it was ELISA positive for HTLV-1/2.The patient had a good initial response to a CHOP scheme (cyclophosphamide, doxorubicin, vincristine and prednisone) with filgrastim. However, the patient had a relapse and died before the second cycle.Comorbidity could lead to the associated risk factors model. According to this model, secondary immunodeficiency caused by HTLV-1 may induce the development of verrucous carcinomas; alternatively, the disease could be due to a correlation between HTLV-1 and the human papillomavirus (HPV).La leucemia/linfoma de células T del adulto se clasifica como una neoplasia de células T CD4+ periféricas desencadenada por el virus linfotrópico de células T humanas tipo 1 (HTLV-1). Los síntomas típicos se asocian a la infiltración leucémica; sin embargo, también se ha descrito la manifestación atípica y exagerada de carcinomas verrucosos.Se presenta el caso de una paciente con lesiones múltiples en piel, necrosis isquemica del hallux y linfadenopatías. se realizaron biopsias que reportaron carcinoma epidermoide verrugoso y linfoma cutáneo. Se detectó esplenomegalia y adenopatías en mesenterio, región retroperitoneal, y cadenas ganglionares de las extremidades. la medula ósea presentó hallazgos compatibles con leucemia/linfoma de células T y ELISA positivo para HTLV-1/2.La paciente presentó buena respuesta inicial al esquema CHOP (ciclofosfamida, doxorrubicina, vincristina, prednisona) con filgrastim. Sin embargo, presentó recaída de la enfermedad antes del segundo ciclo y falleció.La comorbilidad podría conducir al modelo de factores de riesgo asociados. De acuerdo con este modelo, la inmunodeficiencia secundaria causada por HTLV-1 puede inducir el desarrollo de carcinomas verrucosos; Alternativamente, la enfermedad podría deberse a una correlación entre el HTLV-1 y el virus del papiloma humano (VPH).

Adult T-cell leukemia/lymphoma (ATL) is an aggressive hematological malignancy caused by human T-cell leukemia virus type-1 (HTLV-1). ATL is preceded by decades of chronic HTLV-1 infection, and the tumors carry both somatic mutations and proviral DNA integrated into the tumor genome. In order to gain insight into the oncogenic process, we used targeted sequencing to track the evolution of the malignant clone in 6 individuals, 2 to 10 years before the diagnosis of ATL. Clones of premalignant HTLV-1–infected cells bearing known driver mutations were detected in the blood up to 10 years before individuals developed acute and lymphoma subtype ATL. Six months before diagnosis, the total number and variant allele fraction of mutations increased in the blood. Peripheral blood mononuclear cells from premalignant cases (1 year prediagnosis) had significantly higher mutational burden in genes frequently mutated in ATL than did high-risk, age-matched HTLV-1 carriers who remained ATL-free after a median of 10 years of follow-up. These data show that HTLV-1–infected T-cell clones carrying key oncogenic driver mutations can be detected in cases of ATL years before the onset of symptoms. Early detection of such mutations may enable earlier and more effective intervention to prevent the development of ATL.

Human T-cell lymphotropic virus type 1 (HTLV-1) Tax oncoprotein is required for viral gene expression. Tax transactivates the viral promoter by recruiting specific transcription factors but also by interfering with general transcription factors involved in the preinitiation step, such as TFIIA and TFIID. However, data are lacking regarding Tax interplay with TFIIH, which intervenes during the last step of preinitiation. We previously reported that XPB, the TFIIH subunit responsible for promoter opening and promoter escape, is required for Tat-induced human-immunodeficiency virus promoter transactivation. Here, we investigated whether XPB may also play a role in HTLV-1 transcription. We report that Tax and XPB directly interact in vitro and that endogenous XPB produced by HTLV-1-infected T cells binds to Tax and is recruited on proviral LTRs. In contrast, XPB recruitment at the LTR is not detected in Tax-negative HTLV-1-infected T cells and is strongly reduced when Tax-induced HTLV-1 LTR transactivation is blocked. XPB overexpression does not affect basal HTLV-1 promoter activation but enhances Tax-mediated transactivation in T cells. Conversely, downregulating XPB strongly reduces Tax-mediated transactivation. Importantly, spironolactone (SP)-mediated inhibition of LTR activation can be rescued by overexpressing XPB but not XPD, another TFIIH subunit. Furthermore, an XPB mutant defective for the ATPase activity responsible for promoter opening does not show rescue of the effect of SP. Finally, XPB downregulation reduces viability of Tax-positive but not Tax-negative HTLV-1-transformed T cell lines. These findings reveal that XPB is a novel cellular cofactor hijacked by Tax to facilitate HTLV-1 transcription., IMPORTANCE HTLV-1 is considered the most potent human oncovirus and is also responsible for severe inflammatory disorders. HTLV-1 transcription is undertaken by RNA polymerase II and is controlled by the viral oncoprotein Tax. Tax transactivates the viral promoter first via the recruitment of CREB and its cofactors to the long terminal repeat (LTR). However, how Tax controls subsequent steps of the transcription process remains unclear. In this study, we explore the link between Tax and the XPB subunit of TFIIH that governs, via its ATPase activity, the promoter-opening step of transcription. We demonstrate that XPB is a novel physical and functional partner of Tax, recruited on HTLV-1 LTR, and required for viral transcription. These findings extend the mechanism of Tax transactivation to the recruitment of TFIIH and reinforce the link between XPB and transactivator-induced viral transcription.

Adult T-cell leukemia/lymphoma (ATLL) is a fatal disease caused by human T-cell leukemia virus type 1 (HTLV-1). We retrospectively analyzed 195 patients with ATLL (lymphomatous n = 96, acute n = 80, unfavorable chronic n = 7, chronic n = 5, smoldering n = 3, and unclassified n = 4) diagnosed between 1987 and 2016 (median age 52 years, 77% Afro-Caribbean). Hypercalcemia was associated with acute ATLL (65%, vs 23% lymphomatous) (P = .012). The median survival for patients treated with modern therapies between 2000 and 2016 was 4.1 months for acute, 10.2 months for lymphomatous, 72 months for chronic/smoldering, and not reached for unfavorable chronic type, with 4-year survival rates of 10%, 4%, 60%, and 83%, respectively. The overall response rate (ORR) after first-line multiagent chemotherapy was 78% (complete response [CR] 39%) for acute vs 67% (CR 33%) for lymphomatous ATLL. First-line zidovudine interferon-α (AZT-IFN) resulted in ORR of 56% (CR 23%) for acute (n = 43), 33% (CR 16.5%) for lymphomatous (n = 6), and 86% (CR 29%) for unfavorable chronic ATLL. The median progression-free survival (PFS) in patients with aggressive ATLL who achieved CR after AZT-IFN was 48 months vs 11 months after chemotherapy (P = .003). Allogeneic hematopoietic stem cell transplant (allo-HSCT) resulted in a PFS of 24 and 28 months in 2 patients with lymphomatous ATLL. Our results suggest high-dose AZT-IFN is a reasonable up-front option for patients with aggressive leukemic ATLL followed by chemotherapy switch in nonresponders, whereas chemotherapy should be used in lymphomatous type followed by allo-HSCT when feasible.

International audience; Several studies have revealed that endosomal sorting controls the steady-state levels of Notch at the cell surface in normal cells and prevents its inappropriate activation in the absence of ligands. However, whether this highly dynamic physiologic process can be exploited to counteract dysregulated Notch signaling in cancer cells remains unknown. T-ALL is a malignancy characterized by aberrant Notch signaling, sustained by activating mutations in Notch1 as well as overexpression of Notch3, a Notch paralog physiologically subjected to lysosome-dependent degradation in human cancer cells. Here we show that treatment with the pan-HDAC inhibitor Trichostatin A (TSA) strongly decreases Notch3 full-length protein levels in T-ALL cell lines and primary human T-ALL cells xenografted in mice without substantially reducing NOTCH3 mRNA levels. Moreover, TSA markedly reduced the levels of Notch target genes, including pTα, CR2, and DTX-1, and induced apoptosis of T-ALL cells. We further observed that Notch3 was post-translationally regulated following TSA treatment, with reduced Notch3 surface levels and increased accumulation of Notch3 protein in the lysosomal compartment. Surface Notch3 levels were rescued by inhibition of dynein with ciliobrevin D. Pharmacologic studies with HDAC1, 6, and 8-specific inhibitors disclosed that these effects were largely due to inhibition of HDAC6 in T-ALL cells. HDAC6 silencing by specific shRNA was followed by reduced Notch3 expression and increased apoptosis of T-ALL cells. Finally, HDAC6 silencing impaired leukemia outgrowth in mice, associated with reduction of Notch3 full-length protein in vivo. These results connect HDAC6 activity to regulation of total and surface Notch3 levels and suggest HDAC6 as a potential novel therapeutic target to lower Notch signaling in T-ALL and other Notch3-addicted tumors.

Human T-lymphotropic virus-1 (HTLV-1) can cause adult T-cell leukemia/ lymphoma (ATL/L), which is a rare and aggressive type of blood cancer. Herein, we report a case of ATL/L in a middle-aged man with unusual jaw presentations. The patient presented with mandibular, maxillary and palatal bony hard expansion, accompanied by generalized tooth mobility six months prior to admission to the Department of Oral Medicine. The panoramic radiograph showed generalized rarefaction of jaw bones. After laboratory examinations and bone marrow aspiration, ATL/L was diagnosed in association with HTLV-1. The patient underwent chemotherapy. Although the majority of infections associated with HTLV-1 are asymptomatic, some patients may develop blood diseases such as ATL/L and neurological disorders, mainly HTLV-1 associated myelopathy and tropical spastic paraparesis. ATL/L is a rare hematological malignancy in oral cavity that should be included in the differential diagnosis of cases with jaw swelling or generalized demineralization. Serum levels of anti-HTLV-1 antibodies should be examined in suspicious patients, particularly in endemic regions.

Current first-line treatment for Adult T-cell leukemia (ATL) includes combination therapy with interferon alpha (IFN-α) and zidovudine (AZT). The use of IFN-α in this treatment is mostly empirical in origin, whereas the therapeutic potential of interferon beta (IFN-β), has not yet been thoroughly explored in this context. Here we compare the effects of IFN-α and IFN-β treatment in short term ex vivo peripheral blood mononuclear cell (PBMC) cultures from 22 ATL patients. Using proliferation, apoptosis and antiviral bioassays, complemented with microarray and gene set analysis, we demonstrate that in this setting IFN-β has superior antiproliferative and pro‑apoptotic effects than IFN-α. Increased p53 signaling is observed under the IFN-β treatment, while the antiviral effects are equivalent to those of IFN-α treatment. Notably, the genes in a published in vivo AZT/IFN-α response profile are affected more strongly by IFN-β than by IFN-α stimulus in these ex vivo PBMCs. In conclusion, this first comprehensive analysis comparing the effects of IFN-α and IFN-β on ex vivo PBMCs of ATL patients demonstrates that IFN-β has a greater impact than IFN-α on biological processes which have been shown to be crucial in the treatment of ATL, making IFN-β an intriguing candidate for further in vivo testing. ispartof: Blood Cancer Journal vol:7 issue:1 ispartof: location:United States status: published

Background: Adult T-cell Leukemia/Lymphoma (ATLL) is classified as a peripheral CD4+ T-cell neoplasm caused by the human T-cell lymphotropic virus type 1 (HTLV-1). Typical symptoms are associated with leukemic infiltration; however, atypical and exaggerated manifestations of verrucous carcinoma have also been described. Case report: We present here the case of a patient with multiple skin lesions, ischemic necrosis in the hallux and lymphadenopathies. Biopsies were taken, which showed verrucous epidermal carcinoma and cutaneous lymphoma. Splenomegaly and adenopathy in mesentery, retro peritoneum and lymph node chains in the limbs were observed. Bone marrow examination showed findings compatible with T-cell leukemia/lymphoma; and it was ELISA positive for HTLV-1/2. Treatment and outcome: The patient had a good initial response to a CHOP scheme (cyclophosphamide, doxorubicin, vincristine and prednisone) with filgrastim. However, the patient had a relapse and died before the second cycle. Clinical relevance: Comorbidity could lead to the associated risk factors model. According to this model, secondary immunodeficiency caused by HTLV-1 may induce the development of verrucous carcinomas; alternatively, the disease could be due to a correlation between HTLV-1 and the human papillomavirus (HPV). Resumen Antecedentes: La leucemia/linfoma de células T del adulto se clasifica como una neoplasia de células T CD4+ periféricas desencadenada por el virus linfotrópico de células T humanas tipo 1 (HTLV-1). Los síntomas típicos se asocian a la infiltración leucémica; sin embargo, también se ha descrito la manifestación atípica y exagerada de carcinomas verrugosos. Caso clínico: Se presenta el caso de una paciente con lesiones múltiples en piel, necrosis isquemica del hallux y linfadenopatías. se realizaron biopsias que reportaron carcinoma epidermoide verrugoso y linfoma cutáneo. Se detectó esplenomegalia y adenopatías en mesenterio, región retroperitoneal, y cadenas ganglionares de las extremidades. la medula ósea presentó hallazgos compatibles con leucemia/linfoma de células T y ELISA positivo para HTLV-1/2. Tratamiento y resultado: La paciente presentó buena respuesta inicial al esquema CHOP (ciclofosfamida, doxorrubicina, vincristina, prednisona) con filgrastim. Sin embargo, presentó recaída de la enfermedad antes del segundo ciclo y falleció Relevancia clinica: La comorbilidad podría conducir al modelo de factores de riesgo asociados. De acuerdo con este modelo, la inmunodeficiencia secundaria causada por HTLV-1 puede inducir el desarrollo de carcinomas verrugosos; Alternativamente, la enfermedad podría deberse a una correlación entre el HTLV-1 y el virus del papiloma humano (VPH).

Adult T cell leukemia/lymphoma (ATL), a human T lymphotropic virus type 1 (HTLV-1) –associated disease, has a highly variable clinical course and four subtypes with therapeutic and prognostic implications. However, there are overlapping features between ATL subtypes and between ATL and non-malignant (non-ATL) HTLV-1 infection complicating diagnosis and prognostication. To further refine the diagnosis and prognosis of ATL we characterized the immunophenotype of HTLV-1-infected cells in ATL and non-ATL. A retrospective study of peripheral blood samples from ten HTLV-1-uninfected subjects (UI), 54 HTLV-1infected patients with non-ATL and 22 with ATL was performed using flow cytometry. All patients with ATL had CD4+CCR4+CD26- immunophenotype and the frequency of CD4+CCR4+CD26- T cells correlated highly significantly with the proviral load in non-ATL suggesting CD4+CCR4+CD26- as a marker of HTLV-1 infected cells. Further immunophenotyping of CD4+CCR4+CD26- cells revealed that 95% patients with ATL had a CD7- (≤ 30% CD7+ cells) whereas 95% HTLV+ non-ATL had CD7+ (>30% CD7+ cells) immunophenotype. All patients with aggressive ATL had a CCR7+ (≥30%), whereas 92 % with indolent ATL and 100% non-ATL had a CCR7- (

Pediatric T-cell acute lymphoblastic leukemia (T-ALL) is characterized by chromosomal rearrangements possibly enforcing arrest at specific development stages. We studied the relationship between molecular- cytogenetic abnormalities and T-cell development stage to investigate whether arrest at specific stages can explain the prognostic significance of specific abnormalities. We extensively studied 72 pediatric T-ALL cases for genetic abnormalities and expression of transcription factors, NOTCH1 mutations and expression of specific CD markers. HOX11 cases were CD1 positive consistent with a cortical stage, but as 4/5 cases lacked cytoplasmatic-beta expression, developmental arrest may precede beta-selection. HOX11L2 was especially confined to immature and pre- AB developmental stages, but 3/17 HOX11L2 mature cases were restricted to the gamma delta-lineage. TAL1 rearrangements were restricted to the alpha beta-lineage with most cases being TCR-alpha beta positive. NOTCH1 mutations were present in all molecular-cytogenetic subgroups without restriction to a specific developmental stage. CALM-AF10 was associated with early relapse. TAL1 or HOX11L2 rearrangements were associated with trends to good and poor outcomes, respectively. Also cases with high vs low TAL1 expression levels demonstrated a trend toward good outcome. Most cases with lower TAL1 levels were HOX11L2 or CALM-AF10 positive. NOTCH1 mutations did not predict for outcome. Classification into T-cell developmental subgroups was not predictive for outcome.

A major issue in the treatment of T-cell acute lymphoblastic leukemia (T-ALL) is resistance to chemotherapeutic drugs. Multidrug resistance can be caused by ATP-binding cassette (ABC) transporters. The majority of these proteins have not yet been examined in T-ALL. Using a newly developed microarray for the simultaneous quantification of 38 ABC transporter genes, we observed a consistent overexpression of ABCA2/ABCA3 in clinical samples of ALL. Therefore, we analyzed the association of these two genes with drug resistance. Treatment of CCRF-CEM and Jurkat cells with methotrexate, vinblastine, or doxorubicin led to an induction of ABCA3 expression, whereas a significant increase of ABCA2 expression was only observed in Jurkat cells. To study the causal relationship of ABCA2/A3 overexpression with drug resistance, we applied RNA interference (RNAi) technology. RNAi specific for ABCA2 or ABCA3 led to a partial decrease of expression in these two ABC transporters. Upon cotreatment of RNAi for ABCA2 with methotrexate and vinblastine, a partial decrease of ABCA2 expression as well as a simultaneous increase of ABCA3 expression was observed. Vice versa, ABCA3 RNAi plus drugs decreased ABCA3 and increased ABCA2 expression. This indicates that down-regulation of one ABC transporter was compensated by the up-regulation of the other. Application of RNAi for both ABCA2 and ABCA3 resulted in a more efficient reduction of the expression of both transporters. As a consequence, a significant sensitization of cells to cytostatic drugs was achieved. In conclusion, ABCA2 and ABCA3 are expressed in many T-ALL and contribute to drug resistance. [Mol Cancer Ther 2006;5(8):1986–94]

Background: Most human T cell lymphotropic virus type 1 (HTLV-1) infected individuals are asymptomatic, but they commonly present cutaneous lesions that could be considered warning signs of the disease. Aim: To identify the main cutaneous manifestations present in HTLV-1 infected blood donors and compare them with healthy donors. Materials and methods: Two blood donor groups from the blood bank of an emergency hospital were matched according to gender and age. One group was formed by HTLV-1 (+) (cases) and the other by HTLV-1 (-) donors (controls). A blind examiner to the serologic condition, evaluated their cutaneous manifestations. Results: Twenty five cases and 25 controls aged 18 to 60 years (24 females) were evaluated. One or more cutaneous manifestations were found in 24 (96%) cases and in 15 (60%) controls (p< 0.01). Inflammatory cutaneous diseases were found in 19 (76%) cases and in 9 (36%) controls (p< 0.01). Dermatophytosis was found in 18 (72%) cases and in 12 (48%) controls (NS). Conclusions: HTLV-1 infected Chilean subjects have a higher frequency of dermatoses than their healthy counterparts.

Background: Most human T cell lymphotropic virus type 1 (HTLV-1) infected individuals are asymptomatic, but they commonly present cutaneous lesions that could be considered warning signs of the disease. Aim: To identify the main cutaneous manifestations present in HTLV-1 infected blood donors and compare them with healthy donors. Materials and Methods: Two blood donor groups from the blood bank of an emergency hospital were matched according to gender and age. One group was formed by HTLV-1 (+) (cases) and the other by HTLV-1 (-) donors (controls). A blind examiner to the serologic condition, evaluated their cutaneous manifestations. Results: Twenty five cases and 25 controls aged 18 to 60 years (24 females) were evaluated. One or more cutaneous manifestations were found in 24 (96%) cases and in 15 (60%) controls (p < 0.01). Inflammatory cutaneous diseases were found in 19 (76%) cases and in 9 (36%) controls (p < 0.01). Dermatophytosis was found in 18 (72%) cases and in 12 (48%) controls (NS). Conclusions: HTLV-1 infected Chilean subjects have a higher frequency of dermatoses than their healthy counterparts.

A 55-year-old man presented with deep venous thrombosis of his left leg. Laboratory evaluation disclosed macrocytic anaemia and leukocytosis. In the clinical decision process it was not verified whether all symptoms fitted in with the presumptive diagnosis of pernicious anaemia and stomach carcinoma. The ultimate diagnosis was acute lymphocytic leukaemia. A proper evaluation of a peripheral blood smear would have led to this diagnosis earlier.

La leucemia/linfoma de células T del adulto ( Adult T-Cell Leukemia/Lymphoma , ATLL) es una neoplasia maligna de los linfocitos T CD4 maduros, que resulta de la infección con el virus T-linfotrópico humano de tipo 1 (HTLV-1), con varias manifestaciones sistémicas y cutáneas. Se presentan dos casos de leucemia/linfoma de células T del adulto en pacientes del suroccidente de Colombia, cuyos diagnósticos fueron confirmados por histología, inmunohistoquímica, citometría de flujo y pruebas ELISA y Western blot. También, se discute acerca del virus y cómo hacer el diagnóstico en países como el nuestro. Adult T-cell leukemia/lymphoma (ATLL) is a malignant neoplasia of mature CD4+ T lymphocytes,resulting from infection with human T-lymphotropic virus type 1 (HTLV-1), with several systemic and cutaneous manifestations. We present two cases of adult T-cell leukemia/lymphoma, in patients from the Colombian Southwestern region, whose diagnoses were confirmed by histology, immunohistochemistry, flow cytometry, ELISA and Western blot tests. We also discuss about the virus and how to make this diagnosis in countries like Colombia.

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.