RESUMEN
BACKGROUND: Because the cause of liver dysfunction after allogeneic hematopoietic stem cell transplantation (HSCT) is difficult to identify in the early stages, treatment may be delayed. Therefore, early factors associated with unfavorable outcomes of liver dysfunction must be identified. The objective of this study was to identify unfavorable prognostic factors for liver dysfunction during the early period after transplantation. METHODS: We defined liver dysfunction as elevated liver or biliary enzyme levels (corresponding to Grade 2 in the Common Terminology Criteria for Adverse Events version 4.0) within 30 days of transplantation and retrospectively investigated data from 82 patients who had undergone allogeneic HSCT at our center. RESULTS: Elevated liver or biliary enzyme levels were observed in almost half of the patients studied (n=40, 48.7%). Elevated total bilirubin (T-Bil) level was the most frequently observed unfavorable prognostic factor and had the greatest effect on overall survival (OS), progression-free survival (PFS), and non-relapse mortality (NRM) (probability of unfavorable outcome in patients without and with elevated T-Bil level: OS, 58.9% vs. 15.4%, p < 0.001; PFS, 46.4% vs. 15.4%, p < 0.001; NRM, 10.7% vs. 53.8%, p < 0.001). Moreover, the probability of an unfavorable outcome increased in relation to the degree of T-Bil elevation and absence of improvement over time in T-Bil level. CONCLUSION: Elevated T-Bil level was an important marker of outcomes for liver dysfunction after allogeneic HSCT.
Asunto(s)
Bilirrubina/sangre , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hepatopatías/diagnóstico , Hepatopatías/etiología , Adolescente , Adulto , Aloinjertos , Biomarcadores , Femenino , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Acute kidney injury (AKI) and chronic kidney disease (CKD) are considered common complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). OBJECTIVES AND METHOD: In this study, 114 patients who had undergone allo-HSCT were retrospectively analyzed to investigate the risk factors for onset of posttransplant AKI and CKD as defined by the new Kidney Disease Improving Global Outcomes criteria. RESULTS: Seventy-four patients (64.9%) developed AKI and 25 (21.9%) developed CKD. The multivariate analysis showed that the risk factors for developing stage 1 or higher AKI were age ≥46 years at the time of transplant (p = 0.001) and use of ≥3 nephrotoxic drugs (p = 0.036). For CKD, the associated risk factors were disease status other than complete remission at the time of transplantation (p = 0.018) and onset of AKI after transplant (p = 0.035). The 5-year overall survival (OS) was significantly reduced by development of AKI (p < 0.001), but not CKD. Posttransplant AKI significantly increased the 5-year nonrelapse mortality (p < 0.001), whereas posttransplant CKD showed an increasing tendency, but the difference was not significant. CONCLUSIONS: Posttransplant AKI impacts OS, significantly increases the risk of CKD, and is significantly associated with disseminated intravascular coagulation and use of Ë3 nephrotoxic drugs.
Asunto(s)
Lesión Renal Aguda/etiología , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Insuficiencia Renal Crónica/etiología , Lesión Renal Aguda/patología , Adolescente , Adulto , Niño , Femenino , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/patología , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Pronóstico , Inducción de Remisión , Insuficiencia Renal Crónica/patología , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Trasplante Homólogo , Adulto JovenRESUMEN
INTRODUCTION: Acute myelogenous leukemia (AML) in elderly patients is associated with an increased incidence of complications and treatment-related toxicity because of the frequency of comorbid disease and age-related deterioration in organ function. Despite advances in AML treatment in recent years, elderly patients have experienced limited benefit, and their outcomes remain poor. This study aimed to perform a comprehensive gene mutation analysis in elderly AML patients and identify gene mutations that could serve as prognostic factors. METHODS: An analysis of gene mutations was performed for 281 AML patients, including 98 elderly patients aged 65 years or above. RESULTS: Compared to younger AML patients, elderly patients showed a higher frequency of the following gene mutations: TP53 (P = 0.026), PTPN11 (P = 0.006), RUNX1 (P = 0.024), TET2 (P = 0.002), and ASXL1 (P = 0.023). The complete remission rate was significantly lower in DNMT3A mutation-positive cases (4.26%, P = 0.011) and TP53 mutation-positive cases (2.13%, P = 0.031) than in negative cases. The overall survival rate was significantly poorer in cases with FLT3-ITD (P = 0.003), DNMT3A (P = 0.033), or TP53 mutation (P < 0.001). Conversely, cases with PTPN11 mutation (P = 0.014) had a significantly more favorable prognosis. In multivariate analysis, FLT3-ITD (P = 0.011) and TP53 mutation positivity (P = 0.002) were independent poor prognostic factors, as were a performance status of 3 or above (P < 0.001) and poor cytogenetic prognosis (P = 0.001). In contrast, PTPN11 mutation positivity (P = 0.023) was an independent favorable prognosis factor. CONCLUSION: Analysis of gene mutations in elderly AML patients is very important, not only for establishing prognosis, but also for introducing appropriate molecular-targeted treatments.
Asunto(s)
Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Mutación , Proteínas de Neoplasias/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Tasa de SupervivenciaRESUMEN
TP53 gene abnormality has been reported to be an unfavorable prognostic factor in acute myeloid leukemia (AML). However, almost all studies of TP53 gene abnormality so far have been limited to mutation searches in the DNA binding domain. As there have been few reports examining both mutation and deletion over the full-length of the TP53 gene, the clinical characteristics of TP53 gene abnormality have not yet been clearly established. In this study, TP53 gene mutation was observed in 7.3% of the total 412 de novo AML cases (33 mutations in 30 cases), with mutation outside the DNA binding domain in eight cases (27%). TP53 gene deletion was observed in 3.1% of 358 cases. All cases had monoallelic deletion with TP53 gene mutation on the opposite allele. Multivariate analysis demonstrated that TP53 gene mutation in the DNA binding domain and outside the DNA binding domain was an independent poor prognostic factor for overall survival and relapse-free survival among the total cohort and it is also an unfavorable prognostic factor in FLT3-ITD-negative AML cases aged 70 years or below with intermediate cytogenetic prognosis. In stratified treatment, full-length search for TP53 gene mutation is therefore very important.
Asunto(s)
Biomarcadores de Tumor/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Mutación , Proteína p53 Supresora de Tumor/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Análisis Mutacional de ADN , Femenino , Dosificación de Gen , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Isoformas de Proteínas/genética , Secuenciación del Exoma , Adulto JovenRESUMEN
Acute lymphoblastic leukemias (ALL) positive for KMT2A/AFF1 (MLL/AF4) translocation, which constitute 60% of all infant ALL cases, have a poor prognosis even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This poor prognosis is due to one of two factors, either resistance to TNFα, which mediates a graft-versus-leukemia (GVL) response after allo-HSCT, or immune resistance due to upregulated expression of the immune escape factor S100A6. Here, we report an immune stimulatory effect against KMT2A/AFF1-positive ALL cells by treatment with the anti-allergy drug amlexanox, which we found to inhibit S100A6 expression in the presence of TNF-α. In KMT2A/AFF1-positive transgenic (Tg) mice, amlexanox enhanced tumor immunity and lowered the penetrance of leukemia development. Similarly, in a NOD/SCID mouse model of human KMT2A/AFF1-positive ALL, amlexanox broadened GVL responses and extended survival. Our findings show how amlexanox degrades the resistance of KMT2A/AFF1-positive ALL to TNFα by downregulating S100A6 expression, with immediate potential implications for improving clinical management of KMT2A/AFF1-positive ALL. Cancer Res; 77(16); 4426-33. ©2017 AACR.
Asunto(s)
Aminopiridinas/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Proteínas de Ciclo Celular/metabolismo , Proteínas de Unión al ADN/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Proteínas S100/metabolismo , Factores de Elongación Transcripcional/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Animales , Antialérgicos/administración & dosificación , Antialérgicos/farmacología , Proteínas de Ciclo Celular/genética , Proteínas de Unión al ADN/genética , Modelos Animales de Enfermedad , Regulación hacia Abajo , Sinergismo Farmacológico , Humanos , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Ratones Transgénicos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Proteína A6 de Unión a Calcio de la Familia S100 , Proteínas S100/genética , Factores de Elongación Transcripcional/genética , Factor de Necrosis Tumoral alfa/administración & dosificaciónRESUMEN
Adult T-cell leukemia-lymphoma (ATL) caused by human T-lymphotropic virus type 1 (HTLV-1) is generally associated with poor prognosis. The anti-CCR4 antibody mogamulizumab is one of the options for refractory or relapsed ATL. Mogamulizumab is intravenously administered as a single agent at a dose of 1.0 mg/kg once a week for 8 weeks. The overall response rate is reported to be 50%. Reported common adverse events after administration of mogamulizumab are leukocytopenia, infusion reaction, and skin rash. Although rare, mogamulizumab-associated cardiomyopathy has also been reported. HTLV-1 is also associated with a number of diseases, such as HTLV-1-associated myelopathy (HAM). Approximately 0.25% of infected individuals are estimated to develop HAM. HAM is an inflammatory disease of the central nervous system, which is characterized by slowly progressive spastic paresis of bilateral lower limbs and bladder-rectal disorder. Coexistence of ATL and HAM has rarely been reported. Here we present the case of a patient with ATL in whom Takotsubo cardiomyopathy and HAM developed after mogamulizumab administration.
Asunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Virus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Paraparesia Espástica Tropical/inducido químicamente , Cardiomiopatía de Takotsubo/inducido químicamente , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Resultado Fatal , Femenino , HumanosRESUMEN
In recent years, it has been reported that the frequency of DNA-methylation regulatory gene mutations - mutations of the genes that regulate gene expression through DNA methylation - is high in acute myeloid leukemia. The objective of the present study was to elucidate the clinical characteristics and prognosis of acute myeloid leukemia with associated DNA-methylation regulatory gene mutation. We studied 308 patients with acute myeloid leukemia. DNA-methylation regulatory gene mutations were observed in 135 of the 308 cases (43.8%). Acute myeloid leukemia associated with a DNA-methylation regulatory gene mutation was more frequent in older patients (P<0.0001) and in patients with intermediate cytogenetic risk (P<0.0001) accompanied by a high white blood cell count (P=0.0032). DNA-methylation regulatory gene mutation was an unfavorable prognostic factor for overall survival in the whole cohort (P=0.0018), in patients aged ≤70 years, in patients with intermediate cytogenetic risk, and in FLT3-ITD-negative patients (P=0.0409). Among the patients with DNA-methylation regulatory gene mutations, 26.7% were found to have two or more such mutations and prognosis worsened with increasing number of mutations. In multivariate analysis DNA-methylation regulatory gene mutation was an independent unfavorable prognostic factor for overall survival (P=0.0424). However, patients with a DNA-methylation regulatory gene mutation who underwent allogeneic stem cell transplantation in first remission had a significantly better prognosis than those who did not undergo such transplantation (P=0.0254). Our study establishes that DNA-methylation regulatory gene mutation is an important unfavorable prognostic factor in acute myeloid leukemia.
Asunto(s)
Metilación de ADN , Regulación Leucémica de la Expresión Génica , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Mutación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Bandeo Cromosómico , Terapia Combinada , Femenino , Duplicación de Gen , Perfilación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Secuencias Repetidas en Tándem , Resultado del Tratamiento , Adulto Joven , Tirosina Quinasa 3 Similar a fms/genéticaRESUMEN
Objective In hematological malignancy patients, the complication of acute respiratory failure often reaches a degree of severity that necessitates mechanical ventilation. The objective of the present study was to investigate the therapeutic outcomes of mechanical ventilation in hematological malignancy patients with respiratory failure and to analyze the factors that are associated with successful treatment in order to identify the issues that should be addressed in the future. Methods The present study was a retrospective analysis of 71 hematological malignancy patients with non-cardiogenic acute respiratory failure who were treated with mechanical ventilation at Nippon Medical School Hospital between 2003 and 2014. Results Twenty-six patients (36.6%) were treated with mechanical ventilation in an intensive care unit (ICU). Non-invasive positive pressure ventilation (NPPV) was applied in 29 cases (40.8%). The rate of successful mechanical ventilation treatment with NPPV alone was 13.8%. The rate of endotracheal extubation was 17.7%. A univariate analysis revealed that the following factors were associated with the successful extubation of patients who received invasive mechanical ventilation: respiratory management in an ICU (p=0.012); remission of the hematological disease (p=0.011); female gender (p=0.048); low levels of accompanying non-respiratory organ failure (p=0.041); and the non-use of extracorporeal circulation (p=0.005). A subsequent multivariate analysis revealed that respiratory management in an ICU was the only variable associated with successful extubation (p=0.030). Conclusion The outcomes of hematological malignancy patients who receive mechanical ventilation treatment for respiratory failure are very poor. Respiratory management in an ICU environment may be useful in improving the therapeutic outcomes of such patients.
Asunto(s)
Neoplasias Hematológicas/complicaciones , Respiración Artificial/métodos , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia , Enfermedad Aguda , Adulto , Anciano , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Respiración con Presión Positiva/métodos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
We report a case of the extremely rare condition Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease (LPD) which occurred after umbilical cord blood transplantation. A 25-year-old Japanese man underwent cord blood transplantation from a male human leukocyte antigen 4/6-matched donor due to acute myeloid leukemia with trisomy 8. Bone marrow examination on day 30 showed chimerism with at least 90% donor cells and complete hematological response. Chronic symptoms of graft-versus-host disease appeared only on the skin and were successfully treated with cyclosporine alone. Three years later, however, the patient experienced repeated cold-like symptoms and was hospitalized with liver dysfunction. A high fever developed and was followed by significant edema of the right side of the face. The EBV DNA copy number in whole peripheral blood was 2×10(4)/mL. Liver biopsy showed invasion of EBV-infected CD8-positive T cells. Southern blotting analysis of the whole peripheral blood showed that the T-cell receptor Cß1 rearrangement was positive. On the basis of these results, EBV-positive T-cell LPD was diagnosed and treated with prednisolone, cyclosporine, and etoposide, followed by cyclophosphamide, doxorubicin, vincristine, and prednisone. However, the patient died of cardiac function failure, pneumonia, and pulmonary hemorrhage, all of unidentified cause. Most cases of EBV-related LPD after hematopoietic stem cell transplantation consist of EBV-positive B-cell LPD, and, to our knowledge, de novo EBV-positive T-cell LPD subsequent to transplantation has not been previously reported.
Asunto(s)
Linfocitos T CD8-positivos/virología , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Infecciones por Virus de Epstein-Barr/etiología , Herpesvirus Humano 4 , Leucemia Mieloide Aguda/cirugía , Trastornos Linfoproliferativos/etiología , Complicaciones Posoperatorias , Adulto , Linfocitos T CD8-positivos/patología , Resultado Fatal , Humanos , Hígado/patología , Hígado/virología , Trastornos Linfoproliferativos/tratamiento farmacológico , Trastornos Linfoproliferativos/patología , Trastornos Linfoproliferativos/virología , Masculino , Adulto JovenRESUMEN
Acute lymphoblastic leukemia (ALL), a clonal expansion of hematopoietic blasts, is a highly heterogeneous disease comprising many entities for which distinct treatment strategies are pursued. Recurrent defects including chromosomal translocations, aneuploidies, and gene-specific alterations generate molecular subgroups of B- and T-ALL with differing clinical courses and distinct responses to therapy. Herein, we review the spectrum of genetic aberrations that promote acute B- and T-ALL, as well as the currently-revealed mechanisms of cell transformation and malignant progression. Although 5-year overall survival of childhood ALL patients has improved to as much as 90% due to progress in chemotherapy and other supporting therapeutic modalities, including allo-HSCT, the prognosis is still poor for the remaining 10% of cases, which consist mainly of MLL-AF4-positive ALL and bcr-abl positive ALL. The prognosis of adults with ALL is not satisfactory and adult ALL remains a challenging disease. The development of novel methodologies, including new molecular therapeutic targets, is also needed to improve the prognosis of ALL.
Asunto(s)
Leucemia Linfoide/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Translocación Genética/genética , Animales , Proteínas de Fusión bcr-abl/genética , Proteínas de Fusión bcr-abl/metabolismo , Humanos , Leucemia Linfoide/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , PronósticoAsunto(s)
Proteína de la Leucemia Mieloide-Linfoide/genética , Proteínas de Fusión Oncogénica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Animales , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Regulación Leucémica de la Expresión Génica , Genotipo , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Proteínas de Fusión Oncogénica/metabolismo , Fenotipo , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Factores de Tiempo , Regulación hacia ArribaAsunto(s)
Antineoplásicos/farmacología , Proteínas de Fusión bcr-abl/genética , Janus Quinasa 2/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Pirimidinas/farmacología , Tiazoles/farmacología , Adulto , Antineoplásicos/uso terapéutico , Benzamidas/farmacología , Benzamidas/uso terapéutico , Dasatinib , Resistencia a Antineoplásicos/genética , Células Madre Hematopoyéticas/patología , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Mutación , Piperazinas/farmacología , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Tiazoles/uso terapéutico , Translocación GenéticaRESUMEN
Mixed-lineage leukemia (MLL)/AF4-positive acute lymphoblastic leukemia (ALL) is a common type of leukemia in infants, which is associated with a high relapse rate and poor prognosis. IL24 selectively induces apoptosis in cancer cells and exerts immunomodulatory and antiangiogenic effects. We examined the effects of adeno-associated virus type 8 (AAV8) vector-mediated muscle-directed systemic gene therapy in MLL/AF4-positive ALL using IL24. In a series of in vitro studies, we examined the effects of AAV8-IL24-transduced C2C12 cell-conditioned medium. We also examined the effects of AAV8-IL24 in MLL/AF4 transgenic mice. The results revealed the effects of AAV8-IL24 in MLL/AF4-positive ALL both in vitro and in vivo. With regard to the mechanism of therapy using AAV8-IL24 in MLL/AF4-positive ALL, we demonstrated the antiangiogenicity and effects on the ER stress pathway and unreported pathways through inhibition of S100A6 and HOXA9, which is specific to MLL/AF4-positive ALL. Inhibition of S100A6 by IL24 was dependent on TNF-α and induced acetylation of p53 followed by activation of the caspase 8-caspase 3 apoptotic pathway. Inhibition of HOXA9 by IL24, which was independent of TNF-α, induced MEIS1 activation followed by activation of the caspase 8-caspase 3 apoptotic pathway. Thus, gene therapy using AAV8-IL24 is a promising treatment for MLL/AF4-positive ALL.
Asunto(s)
Dependovirus/genética , Modelos Animales de Enfermedad , Terapia Genética , Interleucinas/genética , Proteína de la Leucemia Mieloide-Linfoide/antagonistas & inhibidores , Proteína de la Leucemia Mieloide-Linfoide/genética , Proteínas de Fusión Oncogénica/antagonistas & inhibidores , Proteínas de Fusión Oncogénica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Animales , Apoptosis , Western Blotting , Proteínas de Ciclo Celular/metabolismo , Proliferación Celular , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Fibroblastos/citología , Fibroblastos/metabolismo , Citometría de Flujo , Proteínas de Homeodominio/metabolismo , Humanos , Técnicas para Inmunoenzimas , Masculino , Ratones , Ratones Transgénicos , Mioblastos/citología , Mioblastos/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , ARN Mensajero/genética , Proteína A6 de Unión a Calcio de la Familia S100 , Proteínas S100/metabolismoRESUMEN
Recently, RCSD1 was identified as a novel gene fusion partner of the ABL1 gene. The RCSD1 gene, located at 1q23, is involved in t(1;9)(q23;q34) translocation in acute B lymphoblastic leukemia. Here we describe RCSD1-ABL1-positive B-cell acute lymphoblastic leukemia (ALL) followed by rapid clonal evolution exhibiting three rare reciprocal translocations. We performed breakpoint analysis of the transcript expressed by the RCSD1-ABL1 fusion gene. RT-PCR and sequence analyses detected transcription of a single RCSD1-ABL1 fusion gene variant, which had breakpoints in exon 3 of RCSD1 and exon 4 of ABL1. The RCSD1 portion of the RCSD1-ABL1 fusion transcript consists of exons 1, 2, and 3. Tyrosine kinase inhibitors, imatinib and dasatinib, coadministered with dexamethasone achieved transient clinical effects in the present RCSD1-ABL1-positive ALL. However, leukemic cells rapidly became refractory to this treatment following the subsequent development of three additional reciprocal chromosomal translocations, t(5;16)(q33;q24), dic(18;20)(p11.2;q11.2) and t(10;19)(q24;p13.3). The present RCSD1-ABL1-positive ALL may represent a state of high chromosomal instability.
Asunto(s)
Resistencia a Antineoplásicos/efectos de los fármacos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Leucemia de Células B/genética , Proteínas Proto-Oncogénicas c-abl/metabolismo , Translocación Genética/genética , Cariotipo Anormal , Enfermedad Aguda , Adulto , Secuencia de Bases , Dexametasona/uso terapéutico , Exones , Humanos , Hibridación Fluorescente in Situ , Péptidos y Proteínas de Señalización Intracelular/genética , Leucemia de Células B/tratamiento farmacológico , Leucemia de Células B/metabolismo , Masculino , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-abl/genéticaRESUMEN
Rearrangements of the MLL gene located at 11q23 are common chromosomal abnormalities associated with acute leukemia (AL), especially infant and secondary leukemia after previous treatment with DNA topoisomerase II inhibitors. 11q23/MLL abnormalities have been widely recognized as an important prognostic factor in AL. Over 70 chromosome partners of 11q23 have been identified to date, at least 50 of which have been cloned and characterized at the molecular level. Recent studies showed that the prognosis of 11q23/MLL AL varies widely according to the partner gene, the leukemia cell lineage, the age of the patient and the treatment administered. Special strategies are needed to treat 11q23/MLL AL, including allogeneic hematopoietic stem cell transplantation, according to the fusion partner. The development of novel methodologies, including new molecular therapeutic targets, is also needed to improve the prognosis of 11q23/MLL AL. The present article provides an update on the current status of prognosis and treatment of 11q23/MLL AL according to the fusion partner.
Asunto(s)
Cromosomas Humanos Par 11/genética , Leucemia/genética , Proteína de la Leucemia Mieloide-Linfoide/genética , Fusión Génica , N-Metiltransferasa de Histona-Lisina , Humanos , Leucemia/patología , PronósticoRESUMEN
We report here a rare case of EBV-related post-transplantation lymphoproliferative disorder (PTLD) localized to the skin. The patient was a 64-year-old man diagnosed with angioimmunoblastic T cell lymphoma (AITL). He underwent cord blood transplantation with a reduced intensity conditioning regimen during partial remission after chemotherapy. On day 70 after transplantation, subcutaneous tumors developed near the left scapula and in the left upper arm. Pathological examination of the skin tumor revealed that this tumor was composed of diffuse large centroblast-like cells, the majority of which were CD20 positive, CD 79a positive, CD30 positive and Epstein-Barr virus (EBV) latency-associated RNA (EBER) positive, and EBV-DNA was also detected in tumor cells. At that time, real-time polymerase chain reaction documented no evidence of the EBV genome in his blood. Chimerism analysis revealed that the tumor cells were derived from donor cells, which led to the diagnosis of EBV-related PTLD. For treatment, in addition to decreasing the dose of tacrolimus, we administered rituximab and local irradiation to skin lesions, which led to disappearance of the tumors followed by continued complete remission.