RESUMEN
BACKGROUND: Associations between IKZF1 gene variants and Acute Lymphoblastic Leukemia (ALL) was recently reported. We examined whether the common IKZF1 polymorphisms rs4132601 T/G and rs111978267 A/G are associated with ALL among a Tunisian pediatric cohort. METHODS: This case-control study involved 170 patients with ALL and 150 control subjects. SNP genotyping was performed by TaqMan® SNP Genotyping Assay. RESULTS: The minor allele G of IKZF1 gene polymorphism rs4132601 T/G was significantly higher in ALL cases than in control subjects (P = 0.029), with 1.54-fold increased risk of ALL. The association of rs4132601 with ALL was seen under co-dominant (P = 0.009), recessive (P = 0.006), and additive (P = 0.027) genetic models, of which the co-dominant (P = 0.027) and recessive (P = 0.027) association remained significant after adjusting for covariates, and False Discovery Rate correction. In contrast, no association was noted for rs111978267 variant. Two-locus (rs4132601-rs11978267) IKZF1 haplotype analysis demonstrated association of GA (P = 0.053), with increased ALL risk [OR (95% CI) = 1.58 (1.00-2.51)], which remained significant after controlling for key covariates [aP = 0.046; aOR (95% CI) = 1.61 (1.01-2.57)]. CONCLUSION: We demonstrated the association of IKZF1 polymorphism rs4132601 T/G with increased risk of ALL among Tunisian pediatric cohort, with altered phenotypic changes among ALL patients.
Asunto(s)
Predisposición Genética a la Enfermedad , Factor de Transcripción Ikaros/genética , Polimorfismo de Nucleótido Simple , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Estudios de Casos y Controles , Niño , Estudios de Cohortes , Femenino , Humanos , Masculino , Factores de Riesgo , TúnezRESUMEN
Familial aggregation of hematological malignancies has been reported highlighting inherited genetic predisposition. In this study, we targeted four candidate genes: JAK2 and RUNX1 genes assuring a prominent function in hematological process and CBL and NPM1 as proto-oncogenes. Their disruption was described in several sporadic hematological malignancies. The aim of this study is to determine whether JAK2, CBL, RUNX1, and NPM1 germline genes mutations are involved in familial hematological malignancies. Using direct sequencing, we analyzed JAK2 (exons 12 and 14); CBL (exons 7, 8 and 9); NPM1 (exon 12) and the entire RUNX1 in 88 independent families belonging to Tunisian and French populations. Twenty-one sporadic acute leukemias were included in this study. We reported a heterozygous intronic c.1641 + 6 T > C JAK2 variant (rs182123615) found in two independent familial cases diagnosed with gastric lymphoma and Hodgkin lymphoma. The in silico analysis suggested a potential impact on splicing, but the functional splicing minigene reporter assay on rs182123615 variant showed no aberrant transcripts. In one sporadic acute myeloblastic leukemia, we reported an insertion 846 in. TGTT in exon 12 of NPM1 gene that may impact the normal reading frame. The rs182123615 JAK2 variant was described in several contexts including myeloproliferative neoplasms and congenital erythrocytosis and was supposed to be pathogenic. Through this current study, we established the assessment of pathogenicity of rs182123615 and we classified it rather as rare polymorphism.
Asunto(s)
Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Análisis Mutacional de ADN/métodos , Neoplasias Hematológicas/genética , Janus Quinasa 2/genética , Proteínas Nucleares/genética , Proteínas Proto-Oncogénicas c-cbl/genética , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Variación Genética/genética , Neoplasias Hematológicas/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Nucleofosmina , LinajeRESUMEN
The t (8; 21) (q22; q22) with the resulting RUNX1- RUNX1T1 rearrangement is one of the most common cytogenetic abnormalities in acute myeloid leukemia (AML). It is associated with favorable prognosis. The t (5; 17) (q35; q21) is an uncommon translocation, fuses the gene for the nucleophosmin (NPM) to the retinoic acid receptor α(RARA) and was described essentially in acute promyelocytic leukemia (APL) variant. We present the case of a 19-year-old male patient who developed an AML with t (8; 21) (q22; q22) associated to t (5; 17) (q35; 21). Morphology and immunophenotype of the leukemic cells were compatible with AML. The patient received chemotherapy based on cytarabine and anthracycline without all-trans retinoic acid (ATRA) followed by allogenic stem cell transplantation in first remission. To the best of our knowledge, this is the first report of an association between a rare translocation t (5; 17) and t (8; 21) in AML. In this report, we will discuss the prognosis of this association as well as the treatment.
RESUMEN
Plasmablastic lymphoma (PBL) is a rare clinicopathological entity that still raises many diagnostic and management difficulties, particularly due to the overlap between plasmablastic lymphomas and myeloma features. We report a clinical presentation of PBL affecting bone marrow in a 43-year-old patient who was admitted for B symptoms, hepatosplenomegaly, and bicytopenia investigation. Based on these findings, acute leukemia was suspected. Bone marrow morphology immunohistochemistry and flow cytometry contributed to establishing the diagnosis of medullary PBL. The patient deteriorated and died due to septic shock. This pathology requires collaboration between clinicians, pathologists, and biologists to confirm the diagnosis early. Nevertheless, a delayed diagnosis may contribute to worsening the prognosis particularly due to advanced stage consultation. Our reported case illustrates a rare clinical presentation affecting bone marrow. In our context, a confrontation between flow cytometry and immunohistochemistry was of interest as it helped to detect the immunological features of this neoplasm.
Asunto(s)
Mieloma Múltiple , Linfoma Plasmablástico , Humanos , Adulto , Linfoma Plasmablástico/diagnóstico , Linfoma Plasmablástico/patología , Inmunohistoquímica , Citometría de Flujo , Mieloma Múltiple/diagnóstico , PronósticoRESUMEN
OBJECTIVES: This study aims to identify the presenting symptoms, treatment and outcome of patients with nasal natural killer T (NK/T)-cell lymphoma and to find possible differences in survival based on Ann-Arbor stage and international prognostic index (IPI). PATIENTS AND METHODS: Computed tomography and biopsy results of 23 patients (15 males, 8 females; mean age 41 years; range 22 to 72 years) with extranodal NK/T-cell lymphoma who were treated at the department of clinical hematology between 1995 and 2011 were retrospectively analyzed. RESULTS: The median time from onset of clinical symptoms to histological diagnosis was five months. Most patients presented with nasal obstruction (69%) and rhinism (52%). The site of extranodal NK/T-cell lymphoma primarily involved nasal cavity in 39%. Orbital extension was observed in 26%. Lymphomas were classified as stage IE in 30.4%, stage IIE in 47.8% and stage IVE in 21.7%. Nineteen patients received treatment: 10 received chemotherapy plus radiotherapy, nine received chemotherapy only. We used several regimens of chemotherapy including some protocols containing etoposid, L-asparaginase and others without this drugs. Univariate analysis showed that lower IPI score, low Ann-Arbor stage and responsiveness to treatment with both chemotherapy and radiotherapy were significant factors influencing both OS and PFS. CONCLUSION: Nasal type NK/T-cell lymphoma showed a poor response to the conventional anthracycline-based chemotherapy, thereby an investigation for a novel therapy is urgently needed to improve survival.
Asunto(s)
Linfoma de Células T/mortalidad , Linfoma de Células T/terapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasales/mortalidad , Neoplasias Nasales/terapia , Adulto , Anciano , Femenino , Humanos , Linfoma de Células T/diagnóstico , Masculino , Persona de Mediana Edad , Neoplasias Nasofaríngeas/diagnóstico , Células T Asesinas Naturales , Estadificación de Neoplasias , Neoplasias Nasales/diagnóstico , Pronóstico , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Oral lichen planus is a chronic inflammatory disease of established immune-mediated pathogenesis that affects the oral mucosa. Polycythemia is a nonaggressive myeloproliferative disorder, characterized by an increase in red blood cell mass, often with uncontrolled production of granulocytes and platelets. Their association was rarely mentioned in the scientific literature. The aim of this paper was to report their occurrence in a 52-year-old male patient. Although a casual connection cannot be excluded, both diseases share many similarities in the immune dysfunctions involved in their pathogenesis and their clinical features. Such a hypothesis remains to be demonstrated by further studies. The presence of oral lesions should alert the clinicians in the process of identifying and early diagnosing these diseases. Thus, complications can be prevented and treatment can be started at an early stage, avoiding further damage.
RESUMEN
Fulminant meningococcemia is a relatively rare life-threatening disease caused by Neisseria meningitidis. The clinical presentation is varied, but, when associated with myocarditis, it carries a particularly poor prognosis. We report a case of a patient with fulminant meningococcemia who subsequently developed severe myocardial dysfunction and successfully recovered within a period of 7 days of hospitalization. A 15-year-old girl presented with headache, fever, body ache for 1 day and few ecchymotic rash over her body for 3 hours. Blood cultures confirmed infection with N. meningitidis. After 2 days in the hospital, the patient developed dyspnea, elevated jugular venous pressure and shock. The patient was managed with intravenous ceftriaxone, furosemide and norepinephrine. Over the next 4 days the patient rapidly improved. Meningococcemia complicated by myocarditis has an extremely poor prognosis with high mortality. Our case suggests that recovery from a severe myocardial dysfunction can occur rapidly within a few days. Prompt recognition and management in this case might have contributed to the patient's rapid recovery from myocarditis.
Asunto(s)
Bacteriemia/diagnóstico , Infecciones Meningocócicas/diagnóstico , Miocarditis/diagnóstico , Neisseria meningitidis/aislamiento & purificación , Adolescente , Antibacterianos/administración & dosificación , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Ceftriaxona/administración & dosificación , Diuréticos/administración & dosificación , Femenino , Fiebre/etiología , Furosemida/administración & dosificación , Humanos , Masculino , Infecciones Meningocócicas/tratamiento farmacológico , Infecciones Meningocócicas/microbiología , Miocarditis/tratamiento farmacológico , Miocarditis/etiología , Norepinefrina/administración & dosificación , Resultado del TratamientoRESUMEN
BACKGROUND: Autoimmune hemolytic anemia is rare in children. First-line therapies for this disease consist of corticosteroids and intravenously administered immunoglobulin that are effective in most patients. However, a small proportion of cases (5 to 10%) is refractory to these therapies and may represent a medical emergency, especially when hemolysis is due to warm immunoglobulin M. Recently, reports of the use of rituximab in adult autoimmune diseases have shown promising results. In children, there are few studies on the use of rituximab in the treatment for autoimmune hemolytic anemia, especially on its long-term efficacy and adverse effects. CASE PRESENTATION: Here, we report the case of a 10-year-old Tunisian girl with refractory acute autoimmune hemolytic anemia caused by warm-reactive immunoglobulin A, immunoglobulin G, immunoglobulin M, and C3d autoantibodies. First-line treatments using corticosteroids and intravenously administered immunoglobulin were ineffective in controlling her severe disease. On the other hand, she was successfully treated with rituximab. In fact, her hemolytic anemia improved rapidly and no adverse effects were observed. CONCLUSIONS: The case that we report in this paper shows that rituximab could be an alternative therapeutic option in severe acute autoimmune hemolytic anemia with profound hemolysis refractory to conventional treatment. Moreover, it may preclude the use of plasmapheresis in such an urgent situation with a sustained remission.
Asunto(s)
Anemia Hemolítica Autoinmune/inducido químicamente , Anemia Hemolítica Autoinmune/tratamiento farmacológico , Inmunoglobulinas Intravenosas/efectos adversos , Factores Inmunológicos/administración & dosificación , Rituximab/administración & dosificación , Anemia Hemolítica Autoinmune/diagnóstico , Antígenos CD20 , Transfusión Sanguínea , Niño , Femenino , Humanos , Inmunoglobulina A/administración & dosificación , Inmunoglobulina A/efectos adversos , Inmunoglobulina G/administración & dosificación , Inmunoglobulina G/efectos adversos , Inmunoglobulina M/administración & dosificación , Inmunoglobulina M/efectos adversos , Inmunoglobulinas Intravenosas/administración & dosificación , Factores Inmunológicos/efectos adversos , Recuento de Leucocitos , Inducción de Remisión , Rituximab/efectos adversos , Resultado del TratamientoRESUMEN
INTRODUCTION: Genetic predisposition to familial hematological malignancies was previously described through several epidemiological analyses, but the genetic basis remains unclear. The tumor-suppressor ARLTS1 gene was previously described in sporadic hematological malignancies and familial cancer context. METHODS: In this study, we sequence the ARLTS1 gene in 100 patients belonging to 88 independent Tunisian and French families. RESULTS: After gene sequencing, we report 8 genetic variations, most of which were previously reported in several cancer forms. The most common variants were W149X and C148R and were previously associated to B-cell chronic lymphocytic leukemia and to high-risk of familial breast cancer. CONCLUSIONS: These results emphasize the fact that ARLTS1 gene mutations can be considered as a potential predisposing factor in familial hematological malignancies and other several cancer forms.