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BACKGROUND/OBJECTIVES: The superiority of cholecalciferol (D3) over ergocalciferol (D2) in sustaining serum 25-hydroxy vitamin D (25OHD) levels is controversial. To compare D2 with D3 we performed a single-blind, placebo-controlled randomized trial spanning 11 weeks. SUBJECTS/METHODS: Healthy volunteers (n=33, aged 33.4±6 years) were divided into three groups (n=11, each): D2, D3 and placebo. Treatment started with a loading dose (100,000 IU) followed by 4800 IU/day (d) between d7 and d20 and follow-up until d77. Serum samples were obtained at baseline and at days 3, 7, 14, 21, 35, 49, 63 and 77. RESULTS: Baseline 25OHD values in the D2 group were lower than those in the D3 and placebo groups (P<0.01). Placebo 25OHD levels never changed. As after the loading dose both D2 and D3 groups had reached similar 25OHD levels, we tested equivalence of the area under the concentration × time curve (AUC) between d7 and d77. The AUC was 28.6% higher for D3 compared with D2, and both were higher with respect to placebo. At d77, D2 25OHD levels were higher than those at baseline, but similar to placebo; both were lower than D3 (P<0.04). According to raw data, the elimination half-life of 25OHD was 84 and 111 days under D2 and D3 supplementation, respectively; after subtracting the placebo values, the corresponding figures were 33 and 82 days. CONCLUSIONS: D2 and D3 were equally effective in elevating 25OHD levels after a loading dose. In the long term, D3 seems more appropriate for sustaining 25OHD, which could be relevant for classic and non-classic effects of vitamin D.
Assuntos
25-Hidroxivitamina D 2/sangue , Calcifediol/sangue , Colecalciferol/uso terapêutico , Suplementos Nutricionais , Ergocalciferóis/uso terapêutico , Modelos Biológicos , Deficiência de Vitamina D/prevenção & controle , Adulto , Argentina , Cálcio/sangue , Cálcio/urina , Colecalciferol/efeitos adversos , Colecalciferol/metabolismo , Suplementos Nutricionais/efeitos adversos , Ergocalciferóis/efeitos adversos , Ergocalciferóis/metabolismo , Feminino , Seguimentos , Meia-Vida , Hospitais Universitários , Hospitais Urbanos , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Recursos Humanos em Hospital , Método Simples-Cego , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/urina , Adulto JovemRESUMO
A patient with chronic inflammatory demyelinating polyradiculoneuropathy and systemic lupus erythematosus arising after rubella vaccination was initially treated with plasmapheresis, corticosteroids and intravenous immunoglobulins, with partial response. After shift to rituximab, most clinical symptoms improved markedly, emphasizing the possible role of this monoclonal antibody in conventional therapy-resistant cases.
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Anticorpos Monoclonais Murinos/uso terapêutico , Antirreumáticos/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , Corticosteroides/uso terapêutico , Adulto , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/complicações , Retratamento , Rituximab , Resultado do TratamentoRESUMO
OBJECTIVES: To characterize the IFNbeta1a-regulated gene expression on leukocytes of Multiple Sclerosis (MS) patients using microarrays with whole human genome representation. METHODS: Genes differentially expressed by interferon-beta were identified by a microarray in vitro study performed in leukocytes obtained from 5 MS relapsing-remitting patients. RESULTS: Following the culture of peripheral blood mononuclear cells from MS relapsing-remitting patients for 24 hs with IFNbeta1a, the expression of 868 genes was modified: 545 increased (including CXCL11, CCL8, INDO, IFI27, CFB, CXCL10 and IFIT1) and 323 diminished (including RBP7, SEPT5, RNF8, ADORA2B and FOS). CONCLUSIONS: Since many of them were previously recognized as involved in MS pathogenesis, the IFNbeta1a mechanism of action could imply a compensatory regulation of systems deregulated in MS.
Assuntos
Adjuvantes Imunológicos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Interferon beta/farmacologia , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adolescente , Adulto , Feminino , Perfilação da Expressão Gênica/métodos , Genoma Humano , Humanos , Técnicas In Vitro , Interferon beta-1a , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto JovemRESUMO
OBJECTIVES: Recombinant human interferon-beta (IFN-b) is a well-established treatment for multiple sclerosis (MS). The regulatory process for marketing authorization of biosimilars is currently under debate in certain countries. In the EU, EMEA has clearly defined the process including overarching and product-specific guidelines, which includes clinical testing. Biosimilarity needs to be based on comparability criteria, including at least molecular characterization, biological activity relevant for the therapeutic effect and relative bioavailability ("bioequivalence"). In the case of such complex diseases as MS, where the effect of treatment is not so directly measurable, in vitro tools can provide additional data to support comparability. Genomic microarrays assays might be useful to compare multisource biopharmaceuticals. The aim of the present study was to compare the pharmacodynamic genomic effects (in terms of transcriptional regulation) of two recombinant human IFN-I(2)1a preparations on lymphocytes of multiple sclerosis patients using a whole genome microarray assay. METHODS: We performed an ex vivo whole genome expression profiling of the effect of two preparations of IFN-I(2)1a on non-adherent mononuclears from five relapsing-remitting MS patients analyzing microarrays (CodeLink Human Whole Genome). Patients blood was drawn, PBMCs isolated and cultured in three different conditions: culture medium (control), 1,000 U/ml of IFN-I(2)1a (BLA- (STOFERON, Bio Sidus) and 1,000 U/ml of IFN-I(2)1a (REBIF, Serono) RNA was purified from non-adherent cells (mostly lymphocytes), amplified and hybridized. Raw data were generated by CodeLink proprietary software. Data normalization, quality control and analysis of differential gene expression between treatments were done using linear model for microarray data. Functional annotation analysis of IFN-I(2)1a MS treatment transcription was done using DAVID. RESULTS: Out of the approximately 45,000 human sequences examined, no evidence of differential regulation was found when both treatments were compared (minimum adjusted p-value > 0.999). The IFN-I(2)1a effect differentially regulated the expression of 868 genes. The expression of standard markers such as GTP cyclohidrolase, MxA, and OAS isoenzymes A and B changed as a consequence of the action of IFN-I(2)1a. CONCLUSIONS: This exhaustive and highly sensitive assay did not show differences in the genomic expression profile of these two products under the assayed experimental conditions. These results suggest that this technology might be useful for the initial comparison of biosimilars, being part of a comprehensive comparability program that includes clinical testing.
Assuntos
Perfilação da Expressão Gênica , Interferon beta/farmacologia , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Transcrição Gênica/efeitos dos fármacos , Análise por Conglomerados , Biologia Computacional/métodos , Composição de Medicamentos/métodos , Feminino , Genoma Humano , Humanos , Interferon beta-1a , Interferon beta/genética , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Proteínas Recombinantes/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase ReversaAssuntos
Adenovírus Humanos/fisiologia , Células Epiteliais/metabolismo , Regulação da Expressão Gênica , Análise de Sequência com Séries de Oligonucleotídeos , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Células Epiteliais/virologia , Humanos , Neoplasias Laríngeas/patologia , Fase S/genéticaRESUMO
Subacute sclerosing panencephalitis (SSPE) is a neurodegenerative disorder due to persistent measles virus infection, with high level of measles-specific antibodies in cerebrospinal fluid (CSF). To analyze whether such response arises from a TH2-biased response, the authors determined TH1 (interferon [IFN]-gamma) and TH2 (interleukin [IL]-4 and IL-10) cytokines in CSF, taken at diagnosis, of eight SSPE patients (median age, 57.5 month, range 42 to 76 months). All patients presented IL-10 (median 29.3 pg/ml, range 4.3 to 162 pg/ml), but not IL-4 (<10 pg/ml); only one case showed IFN-gamma (162 pg/ml). These results are consistent with a TH2 bias or with a local, anti-inflammatory or neuroprotective mechanism involving IL-10.
Assuntos
Interleucina-10/líquido cefalorraquidiano , Panencefalite Esclerosante Subaguda/líquido cefalorraquidiano , Panencefalite Esclerosante Subaguda/imunologia , Idade de Início , Pré-Escolar , Feminino , Humanos , Lactente , Interferon gama/líquido cefalorraquidiano , Interleucina-4/líquido cefalorraquidiano , Masculino , Vírus do Sarampo/imunologia , Células Th2/imunologiaRESUMO
In Argentina, vaccines for immuno-preventable diseases are regulated by the national regulatory agency, the Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (the National Administration of Drugs, Food and Medical Devices, or ANMAT) created in 1992 to ensure efficacy and safety of drugs, food and medical devices available in the country, according to Law 16,463 and Decree 150/92. ANMAT has licensed 84 out of 157 vaccines registered in Argentina. Since 1994, ANMAT evaluated, approved and inspected 20 clinical trials with vaccines (1.8% of the 1062 trials approved by the agency since that time). The National System of Pharmaco-vigilance has received 318 communications of eventual adverse post-vaccination events (0.3% of the total). In addition, ANMAT provides support to the National Immunisation Programme. The current procedure is to follow international guidelines in the field, to be prepared for new, rapidly changing scenarios.
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Vacinação/legislação & jurisprudência , Vacinas/normas , Argentina , Órgãos Governamentais , HumanosRESUMO
PROBLEM: To determine the effect of ovarian stimulation on TH1, TH2 and natural killer (NK) lymphocytes, plasma cytokines, leptin and nitrite levels. METHODS: Women with reproductive failure were studied during the implantation window, at baseline (n = 18) and under ovarian stimulation (gonadotropins + progesterone, n = 6). CONTROLS: eight fertile women. Lymphocyte subpopulations and NK function were determined by flow cytometry. Interleukin-2 (IL-2), IL-4, IL-10, IFN-gamma, TNF-alpha, TGF-beta1 and leptin were measured by enzyme immunoassay (EIA); nitrite by the Griess reaction. RESULTS: At baseline, patients had higher values of NK effectors, NK activity and plasma IFN-gamma and IL-2 than controls. Conversely, TGF-beta1 values were lower. Hormones induced leukocytosis. Under stimulation, THI CD4+ cells, NK effectors and function and plasma IFN-gamma and IL-2 decreased, while transforming growth factor (TGF)-beta1 increased. Other variables did not change. CONCLUSION: The abnormal distribution of leukocytes, high TH1 cytokines and a low TGF-beta1 associated with reproductive failure, respond to ovarian stimulation, achieving total or partial normalization.
Assuntos
Gonadotropina Coriônica/farmacologia , Citocinas/sangue , Infertilidade Feminina/terapia , Células Matadoras Naturais/efeitos dos fármacos , Leptina/sangue , Leuprolida/farmacologia , Nitritos/sangue , Indução da Ovulação , Progesterona/farmacologia , Células Th1/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Adulto , Citotoxicidade Imunológica , Feminino , Humanos , Imunofenotipagem , Infertilidade Feminina/sangue , Infertilidade Feminina/imunologia , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-2/sangue , Interleucina-4/sangue , Células Matadoras Naturais/imunologia , Contagem de Linfócitos , Fator de Crescimento Transformador beta/sangue , Fator de Crescimento Transformador beta1 , Fator de Necrose Tumoral alfa/análiseRESUMO
In patients with chronic paracoccidioidomycosis (n = 10), levels of tumor necrosis factor alpha, interleukin-10, and interleukin-2 in serum, measured by enzyme-linked immunosorbent assay (in picograms per milliliter, as mean +/- standard error of the mean), were higher than in normal controls (n = 8): 186 +/- 40 versus 40 +/- 7 (P < 0.05), 203 +/- 95 versus 20 +/- 8 (P = 0.001), and 96.3 +/- 78.57 versus 1.19 +/- 1.19 (P = 0.045), respectively. Gamma interferon and interleukin-4 levels were similar in patients and controls.
Assuntos
Interleucina-10/sangue , Paracoccidioidomicose/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Idoso , Animais , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paracoccidioidomicose/sangueRESUMO
PURPOSE: To examine the inflammatory impact of endovascular and conventional surgery of abdominal aortic aneurysm (AAA) as assessed by the activation of neutrophils and serum levels of pro- and anti-inflammatory cytokines. METHODS: Twenty-four patients undergoing AAA exclusion were treated with either endovascular (n = 14) or conventional (n=10) techniques. Clinical and hematological data, respiratory burst of neutrophils, and the expression of adhesion and activation molecules (CD18, CD11b, CD69, and HLA-DR) were analyzed by flow cytometry. The enzyme-linked immunosorbent assay technique was used to measure proinflammatory cytokine interleukin (IL)-8 and anti-inflammatory cytokines IL-1 receptor antagonist (IL-1RA) and transforming growth factor beta1 (TGF-beta1). RESULTS: All patients, most of whom had normal cytokine values before surgery, were successfully treated. No significant changes were found in surface antigens. Basal respiratory burst was quite heterogeneous; in all cases respiratory burst activity decreased after surgery and remained low throughout the observation period. Despite marked interpatient differences, IL-1RA and IL-8 increased after surgery, whereas TGF-beta1 decreased, although the variation achieved statistical significance only in the conventional group. Elevated IL-1RA returned to normal within 48 hours in the endoluminal group, whereas the level remained high in the conventional group in the last sample. CONCLUSIONS: Despite heterogeneity before surgery, the respiratory burst decreased for most of the patients regardless of the approach, and both techniques increased IL-1RA. Although both procedures seemed to decrease TGF-beta1, the difference was significant only with the conventional approach. IL-1RA levels fell toward basal values quicker in the endograft patients, suggesting that the endoluminal approach was less aggressive.
Assuntos
Angioplastia , Aneurisma da Aorta Abdominal/cirurgia , Citocinas/sangue , Neutrófilos/metabolismo , Explosão Respiratória/fisiologia , Idoso , Idoso de 80 Anos ou mais , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1 , Masculino , Pessoa de Meia-Idade , Sialoglicoproteínas/sangue , Fator de Crescimento Transformador beta/sangue , Fator de Crescimento Transformador beta1 , Resultado do TratamentoRESUMO
VRCTC-310-Onco (crotoxin, a secretory phospholipase A2+cardiotoxin) is under development as an anti-neoplastic agent. Pro-inflammatory cytokines TNF-alpha and interleukin 1 alpha (IL-1alpha) and anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra) were measured with commercial ELISA kits in sera corresponding to 23 cycles with doses between 0.0025 and 0.023 microg/kg body weight, obtained during the phase I trial of VRCTC-310-Onco. Neither serum TNF-alpha nor IL-1alpha did change significantly after VRCTC-310-Onco. Basal IL-1ra was 794 +/- 97 pg/ml, by 3 h it was similar, 651 +/- 99 pg/ml and at 24 h p.i. it increased to 1197 +/- 122 pg/ml (P<0.001). The increase was dose-dependent. The addition of dexamethasone (required to reduce pain with the highest doses) inhibited IL-1alpha and enhanced the induction of IL-1ra by VRCTC-310-Onco. Summing up, in vivo, in humans, in the dose range tested, VRCTC-310-Onco induces IL-1ra, and does not consistently modify IL-1alpha or TNF-alpha serum levels.
Assuntos
Proteínas Cardiotóxicas de Elapídeos/farmacologia , Crotoxina/farmacologia , Interleucina-1/sangue , Fosfolipases A/farmacologia , Sialoglicoproteínas/sangue , Fator de Necrose Tumoral alfa/metabolismo , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Proteínas Cardiotóxicas de Elapídeos/administração & dosagem , Dexametasona/administração & dosagem , Feminino , Humanos , Mediadores da Inflamação/sangue , Proteína Antagonista do Receptor de Interleucina 1 , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Fosfolipases A/administração & dosagem , Fosfolipases A2RESUMO
OBJECTIVE: To investigate serum levels of transforming growth factor-beta1 and interferon-gamma in active ulcerative colitis and to assess changes during treatment. METHODS: We prospectively evaluated serum from 25 patients with untreated active ulcerative colitis and 19 healthy controls. Disease activity score (DAI), serum transforming growth factor-beta1 and interferon-gamma levels were measured at baseline and after 7 days of conventional treatment. Disease activity score and transforming growth factor-beta1 were also assessed at 42 days. RESULTS: Baseline transforming growth factor-beta1 levels were significantly higher in patients than in controls (P < 0.02). On the 7th day, transforming growth factor-beta1 levels increased only in patients who responded (P < 0. 01); variations in transforming growth factor-beta1 levels and disease activity score were inversely correlated (r=- 0.72, P < 0. 001). At day 42, serum transforming growth factor-beta1 decreased significantly compared with the 7th day (P < 0.05). While in controls, interferon-gamma was undetectable; untreated patients had higher, widely variable, levels. At day 7, responders had higher interferon-gamma values than unresponsive cases. Variations in interferon-gamma correlated moderately with changes in transforming growth factor-beta1 (r=0.53, P < 0.05). Cytokine response did not depend upon the type of treatment. CONCLUSIONS: Both transforming growth factor-beta1 and interferon-gamma may play a role in the injury-repair process in active ulcerative colitis. Variations in circulating transforming growth factor-beta1 levels in the first week of treatment seem to be related to the therapeutic response.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Colite Ulcerativa/sangue , Colite Ulcerativa/tratamento farmacológico , Interferon gama/sangue , Sulfassalazina/uso terapêutico , Fator de Crescimento Transformador beta/sangue , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Estudos de Casos e Controles , Colite Ulcerativa/classificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Índice de Gravidade de DoençaRESUMO
To evaluate the toxicity of VRCTC-310-Onco (Crotalus durissus terrificus crotoxin + cardiotoxin from Naja naja atra), 10 Sprague-Dawley rats were implanted with intraperitoneal slow-release devices and subjected to treatment with 0.5 microgram/g body weight/d for 14 days. Biochemical evidence at days 7 and 14 showed blood, muscular, renal and metabolic disturbance, mostly reversed by day 28. No significant changes were found in necropsy. The limited toxicity of i.p. VRCTC-310-Onco in rats deserves further study.
Assuntos
Antineoplásicos/toxicidade , Proteínas Cardiotóxicas de Elapídeos/toxicidade , Crotoxina/toxicidade , Animais , Antineoplásicos/administração & dosagem , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Proteínas Cardiotóxicas de Elapídeos/administração & dosagem , Crotoxina/administração & dosagem , Combinação de Medicamentos , Ingestão de Alimentos/fisiologia , Eritrócitos/efeitos dos fármacos , Bombas de Infusão Implantáveis , Injeções Intraperitoneais , Leucócitos/efeitos dos fármacos , Fígado/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Triglicerídeos/sangue , Equilíbrio Hidroeletrolítico/fisiologiaRESUMO
To determine the distribution of major blood lymphocyte subsets we evaluated blood lymphocytes by flow cytometry in adenovirus-infected infants aged 30-730 d. In addition, interleukin-1-receptor antagonist, interleukin-10 and transforming growth factor-beta1 were measured in serum by enzyme-linked immunosorbent assay. According to clinical parameters, mechanical ventilation and outcome, infections were classified as moderate (n = 15), severe (n = 11) and fatal (n = 12). Controls were 13 healthy children. In severe and fatal infection, T cells (CD5+/CD19-), NK effectors (CD16+), CD4+ T subset and B1 subset of B lymphocytes (CD5+/CD19+) were all significantly decreased. CD8+ cells were decreased in severe but not fatal cases. There was no difference in serum values of interleukin-10; however, fatal cases had high interleukin 1-receptor antagonist values. Interestingly, patients with moderate infection showed significantly increased values of transforming growth factor-beta1. These results demonstrate that life-threatening adenoviral infection is associated with marked abnormalities in blood lymphocyte and cytokine profile.
Assuntos
Infecções por Adenoviridae/sangue , Citocinas/sangue , Subpopulações de Linfócitos , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , FenótipoRESUMO
OBJECTIVE: Decreased bone mineral density is a common finding in untreated celiac disease patients. However, the precise pathophysiology of osteopenia remains incompletely understood. Pathological features of gluten sensitivity are associated with local release of proinflammatory and antiinflammatory cytokines. We investigated the serum levels of IL-1beta, IL-6, and IL-1 receptor antagonist in celiac patients and correlated them with bone density measurements. METHODS: We assessed serum samples of 16 female patients at the time of diagnosis (on an unrestricted diet) and after a mean time of 37 months on a gluten-free diet. At the same time, bone mineral density in the lumbar spine and total skeleton was determined by DEXA. RESULTS: Untreated patients had high serum levels of IL-1beta and IL-6 and normal IL-1-RA. Treatment produced a decrease in median IL-1beta levels (p = NS) and a significant diminution of IL-6 (p < 0.05). On the contrary, IL-1-RA increased significantly after treatment (p < 0.05). Baseline lumbar spine Z-score and IL-6 levels exhibited a significant inverse correlation (r = -0.61; p < 0.01). Patients with more severe baseline osteopenia (< -2 Z-scores) had a significantly lower IL-1-RA than those with less bone compromise (> -2 Z-scores). CONCLUSIONS: Our data demonstrate that the inflammatory process observed in active celiac disease is associated with high serum levels of IL-1beta and IL-6 and normal levels of IL-1-RA. Treatment significantly reduces both proinflammatory cytokines and significantly increases the antiinflammatory one. We also suggest that these cytokines might have a role in the osteopenia associated with celiac disease.
Assuntos
Doenças Ósseas Metabólicas/imunologia , Doença Celíaca/imunologia , Interleucina-1/sangue , Interleucina-6/sangue , Receptores de Interleucina-1/antagonistas & inibidores , Absorciometria de Fóton , Adolescente , Adulto , Idoso , Densidade Óssea , Doenças Ósseas Metabólicas/sangue , Doença Celíaca/sangue , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
The putative tumor-suppressor gene p16 was mapped to human chromosome 9p21, close to the interferon alpha cluster. The frequency and association of gene alterations of p16, interferon alpha and interferon beta were investigated in a total of 39 Acute Lymphoblastic Leukemia (ALL) patients. Of these, 10 patients (25.6%) presented abnormalities of at least one of the three genes studied. In 32 ALL cases studies of the three genes could be accomplished. In 23 out of 32 ALL cases the 3 genes studied were normally preserved. In the remaining 9 ALL, p16 was affected in 8 cases by homozygous deletions. In 2 patients, p16 deletion was associated with homozygous deletions for interferon alpha and interferon beta genes and in 1 case with total deletion of interferon beta 1 gene and partial deletion of interferon alpha. In the remaining 5 cases, p16 was the only gene deleted with no alteration of type I interferon genes. These data indicate that p16 gene is deleted in a higher frequency than type I interferon genes in ALL. Moreover, within the ALL group with p16 gene deletion, 37.5% are associated with interferon deletions and in general, ALL with alpha and/or beta interferon gene deletions are associated with p16 deletions. Therefore, p16 gene deletion with preserved type I interferon genes in some ALL suggests that the absence of this cdk inhibitor may disturb the normal cell cycle and favor blast transformation.